CN116669703A - New use of immunogenic or vaccine compositions - Google Patents
New use of immunogenic or vaccine compositions Download PDFInfo
- Publication number
- CN116669703A CN116669703A CN202280007011.5A CN202280007011A CN116669703A CN 116669703 A CN116669703 A CN 116669703A CN 202280007011 A CN202280007011 A CN 202280007011A CN 116669703 A CN116669703 A CN 116669703A
- Authority
- CN
- China
- Prior art keywords
- immunogenic
- vaccine composition
- pathogen
- virus
- composition according
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 112
- 229960005486 vaccine Drugs 0.000 title claims abstract description 107
- 230000002163 immunogen Effects 0.000 title claims abstract description 80
- 210000004877 mucosa Anatomy 0.000 claims abstract description 72
- 244000052769 pathogen Species 0.000 claims abstract description 69
- 208000015181 infectious disease Diseases 0.000 claims abstract description 59
- 230000001717 pathogenic effect Effects 0.000 claims abstract description 58
- 239000003550 marker Substances 0.000 claims abstract description 19
- 230000002265 prevention Effects 0.000 claims abstract description 12
- 238000011282 treatment Methods 0.000 claims abstract description 12
- 241000700605 Viruses Species 0.000 claims description 68
- 241000894006 Bacteria Species 0.000 claims description 61
- 239000000427 antigen Substances 0.000 claims description 30
- 108091007433 antigens Proteins 0.000 claims description 30
- 102000036639 antigens Human genes 0.000 claims description 30
- 244000045947 parasite Species 0.000 claims description 27
- 241000233866 Fungi Species 0.000 claims description 24
- 239000000126 substance Substances 0.000 claims description 23
- 230000028993 immune response Effects 0.000 claims description 18
- 102000029797 Prion Human genes 0.000 claims description 12
- 108091000054 Prion Proteins 0.000 claims description 12
- 230000002238 attenuated effect Effects 0.000 claims description 12
- 230000001580 bacterial effect Effects 0.000 claims description 12
- 239000000688 bacterial toxin Substances 0.000 claims description 10
- 239000012634 fragment Substances 0.000 claims description 10
- 208000035143 Bacterial infection Diseases 0.000 claims description 9
- 208000036142 Viral infection Diseases 0.000 claims description 9
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 9
- 230000009385 viral infection Effects 0.000 claims description 9
- 244000005700 microbiome Species 0.000 claims description 8
- 102000053602 DNA Human genes 0.000 claims description 7
- 108020004414 DNA Proteins 0.000 claims description 7
- 230000003612 virological effect Effects 0.000 claims description 7
- 231100000699 Bacterial toxin Toxicity 0.000 claims description 6
- 241001465754 Metazoa Species 0.000 claims description 6
- 241000191967 Staphylococcus aureus Species 0.000 claims description 6
- 239000003755 preservative agent Substances 0.000 claims description 6
- 102000018697 Membrane Proteins Human genes 0.000 claims description 5
- 108010052285 Membrane Proteins Proteins 0.000 claims description 5
- 206010013023 diphtheria Diseases 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 5
- 241000711573 Coronaviridae Species 0.000 claims description 4
- 108010058643 Fungal Proteins Proteins 0.000 claims description 4
- 208000007514 Herpes zoster Diseases 0.000 claims description 4
- 208000000474 Poliomyelitis Diseases 0.000 claims description 4
- 239000000499 gel Substances 0.000 claims description 4
- 230000003071 parasitic effect Effects 0.000 claims description 4
- 241000224489 Amoeba Species 0.000 claims description 3
- 241000701806 Human papillomavirus Species 0.000 claims description 3
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 claims description 3
- 241000710842 Japanese encephalitis virus Species 0.000 claims description 3
- 201000005702 Pertussis Diseases 0.000 claims description 3
- 206010043376 Tetanus Diseases 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 3
- 239000003086 colorant Substances 0.000 claims description 3
- 108020001507 fusion proteins Proteins 0.000 claims description 3
- 102000037865 fusion proteins Human genes 0.000 claims description 3
- 206010022000 influenza Diseases 0.000 claims description 3
- 239000002636 mycotoxin Substances 0.000 claims description 3
- 239000002105 nanoparticle Substances 0.000 claims description 3
- 229920002477 rna polymer Polymers 0.000 claims description 3
- 239000004094 surface-active agent Substances 0.000 claims description 3
- 206010008631 Cholera Diseases 0.000 claims description 2
- 206010014596 Encephalitis Japanese B Diseases 0.000 claims description 2
- 101710091045 Envelope protein Proteins 0.000 claims description 2
- 206010017533 Fungal infection Diseases 0.000 claims description 2
- 206010017913 Gastroenteritis rotavirus Diseases 0.000 claims description 2
- 108060003393 Granulin Proteins 0.000 claims description 2
- 201000005807 Japanese encephalitis Diseases 0.000 claims description 2
- 208000016604 Lyme disease Diseases 0.000 claims description 2
- 201000005505 Measles Diseases 0.000 claims description 2
- 208000005647 Mumps Diseases 0.000 claims description 2
- 208000024777 Prion disease Diseases 0.000 claims description 2
- 101710188315 Protein X Proteins 0.000 claims description 2
- 206010039438 Salmonella Infections Diseases 0.000 claims description 2
- 102100021696 Syncytin-1 Human genes 0.000 claims description 2
- 208000037386 Typhoid Diseases 0.000 claims description 2
- 208000003152 Yellow Fever Diseases 0.000 claims description 2
- 230000000996 additive effect Effects 0.000 claims description 2
- 208000024386 fungal infectious disease Diseases 0.000 claims description 2
- 201000006747 infectious mononucleosis Diseases 0.000 claims description 2
- 201000004792 malaria Diseases 0.000 claims description 2
- 208000010805 mumps infectious disease Diseases 0.000 claims description 2
- 239000002245 particle Substances 0.000 claims description 2
- 239000013612 plasmid Substances 0.000 claims description 2
- 201000005404 rubella Diseases 0.000 claims description 2
- 206010039447 salmonellosis Diseases 0.000 claims description 2
- 208000006379 syphilis Diseases 0.000 claims description 2
- 102000035160 transmembrane proteins Human genes 0.000 claims description 2
- 108091005703 transmembrane proteins Proteins 0.000 claims description 2
- 201000008827 tuberculosis Diseases 0.000 claims description 2
- 201000008297 typhoid fever Diseases 0.000 claims description 2
- 208000006454 hepatitis Diseases 0.000 claims 1
- 231100000283 hepatitis Toxicity 0.000 claims 1
- 241000699800 Cricetinae Species 0.000 description 34
- 102000004169 proteins and genes Human genes 0.000 description 28
- 108090000623 proteins and genes Proteins 0.000 description 28
- 241001678559 COVID-19 virus Species 0.000 description 26
- 230000036039 immunity Effects 0.000 description 19
- 210000001508 eye Anatomy 0.000 description 15
- 108010077805 Bacterial Proteins Proteins 0.000 description 12
- 238000002255 vaccination Methods 0.000 description 11
- 201000010099 disease Diseases 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 230000009885 systemic effect Effects 0.000 description 9
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 108010067390 Viral Proteins Proteins 0.000 description 5
- 230000000903 blocking effect Effects 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 210000000795 conjunctiva Anatomy 0.000 description 5
- 239000003889 eye drop Substances 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 241000941423 Grom virus Species 0.000 description 4
- 108010021466 Mutant Proteins Proteins 0.000 description 4
- 102000008300 Mutant Proteins Human genes 0.000 description 4
- 238000011109 contamination Methods 0.000 description 4
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 4
- 229940012356 eye drops Drugs 0.000 description 4
- 230000002538 fungal effect Effects 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 230000003053 immunization Effects 0.000 description 4
- 238000002649 immunization Methods 0.000 description 4
- 210000003563 lymphoid tissue Anatomy 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 230000002335 preservative effect Effects 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
- 239000013603 viral vector Substances 0.000 description 4
- 241000193449 Clostridium tetani Species 0.000 description 3
- 241000607142 Salmonella Species 0.000 description 3
- -1 are found in nature) Proteins 0.000 description 3
- 230000005540 biological transmission Effects 0.000 description 3
- 239000006196 drop Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 238000011081 inoculation Methods 0.000 description 3
- 230000009545 invasion Effects 0.000 description 3
- 210000004400 mucous membrane Anatomy 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 230000003362 replicative effect Effects 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 241000712461 unidentified influenza virus Species 0.000 description 3
- 229940118696 vibrio cholerae Drugs 0.000 description 3
- 241000588807 Bordetella Species 0.000 description 2
- 241000589969 Borreliella burgdorferi Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 241000282339 Mustela Species 0.000 description 2
- 241000186359 Mycobacterium Species 0.000 description 2
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 241000589884 Treponema pallidum Species 0.000 description 2
- 241000607626 Vibrio cholerae Species 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 230000002146 bilateral effect Effects 0.000 description 2
- 210000001217 buttock Anatomy 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 229940001442 combination vaccine Drugs 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 208000005252 hepatitis A Diseases 0.000 description 2
- 208000002672 hepatitis B Diseases 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000000415 inactivating effect Effects 0.000 description 2
- 239000012678 infectious agent Substances 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 206010023332 keratitis Diseases 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004083 nasolacrimal duct Anatomy 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- UXOWGYHJODZGMF-QORCZRPOSA-N Aliskiren Chemical compound COCCCOC1=CC(C[C@@H](C[C@H](N)[C@@H](O)C[C@@H](C(C)C)C(=O)NCC(C)(C)C(N)=O)C(C)C)=CC=C1OC UXOWGYHJODZGMF-QORCZRPOSA-N 0.000 description 1
- 241000710929 Alphavirus Species 0.000 description 1
- 102000053723 Angiotensin-converting enzyme 2 Human genes 0.000 description 1
- 108090000975 Angiotensin-converting enzyme 2 Proteins 0.000 description 1
- 229940022962 COVID-19 vaccine Drugs 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- 241000186225 Corynebacterium pseudotuberculosis Species 0.000 description 1
- 241000918600 Corynebacterium ulcerans Species 0.000 description 1
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 1
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 241000712079 Measles morbillivirus Species 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- 206010065764 Mucosal infection Diseases 0.000 description 1
- 206010028116 Mucosal inflammation Diseases 0.000 description 1
- 241000711386 Mumps virus Species 0.000 description 1
- 231100000678 Mycotoxin Toxicity 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- 229940096437 Protein S Drugs 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 241000702670 Rotavirus Species 0.000 description 1
- 241000710799 Rubella virus Species 0.000 description 1
- 241000315672 SARS coronavirus Species 0.000 description 1
- 241000293871 Salmonella enterica subsp. enterica serovar Typhi Species 0.000 description 1
- 241000593989 Scardinius erythrophthalmus Species 0.000 description 1
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 101710198474 Spike protein Proteins 0.000 description 1
- 241000589970 Spirochaetales Species 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 208000032481 Vaccination error Diseases 0.000 description 1
- 108010003533 Viral Envelope Proteins Proteins 0.000 description 1
- 241000710772 Yellow fever virus Species 0.000 description 1
- 208000025087 Yersinia pseudotuberculosis infectious disease Diseases 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 229960004601 aliskiren Drugs 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 229960000190 bacillus calmette–guérin vaccine Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 230000036449 good health Effects 0.000 description 1
- 108010037896 heparin-binding hemagglutinin Proteins 0.000 description 1
- 201000010284 hepatitis E Diseases 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 108700021021 mRNA Vaccine Proteins 0.000 description 1
- 229940126582 mRNA vaccine Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 230000037125 natural defense Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000009340 pathogen transmission Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 229960001539 poliomyelitis vaccine Drugs 0.000 description 1
- 239000006041 probiotic Substances 0.000 description 1
- 235000018291 probiotics Nutrition 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 210000004994 reproductive system Anatomy 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000020029 respiratory tract infectious disease Diseases 0.000 description 1
- 230000009291 secondary effect Effects 0.000 description 1
- 208000018196 severe conjunctivitis Diseases 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 244000052613 viral pathogen Species 0.000 description 1
- 229940023147 viral vector vaccine Drugs 0.000 description 1
- 229940051021 yellow-fever virus Drugs 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The present invention relates to an immunogenic or vaccine composition comprising a marker for the prevention and/or treatment of infections caused by at least one pathogen, characterized in that it is applied to the ocular mucosa and/or to the genitourinary mucosa.
Description
Background
In addition to the systemic immune system, our body also contains a mucosa-associated immune system (called MALT, mucosa-associated lymphoid tissue). The mucosa locally contains its own immune system, for example in the digestive tract (GALT, intestinal-related lymphoid tissue), in the nose (NALT, nasal-related lymphoid tissue) or even in the eye (GALT, conjunctival-related lymphoid tissue).
In fact, the site of entry of pathogens into the body is typically near the mucosa of the eye, nose, mouth or gastrointestinal tract. Thus, our body contains a large number of cellular and biochemical defense mechanisms directly on these mucous membranes, which are activated upon contact with pathogens. Typically, the mucosal immune system includes epithelial cells, innate immune cells, and dendritic cells, which are the interface between innate immunity and specific (acquired) immunity. Thus, the mucosa may contain innate immune cells, immunocompetent cells, memory cells and antibody producing cells.
In the case where the pathogen colonizes the mucosa and is highly infectious, the pathogen rapidly breeds after colonization of the mucosa, so that the infection of the mucosa and deeper layers progresses faster than the organism can establish effective immunity to eliminate the pathogen. This is typical of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In fact, covd-19 (or 2019 coronavirus disease) manifests itself mainly as mucosal infections and inflammations, with secondary severe systemic diseases, as well as influenza, herpes or poliomyelitis.
After experiencing a primary infection by a pathogen, the body develops a systemic (serum) immunity against the pathogen. Furthermore, if the pathogen comes into contact with the mucosa of the body, mucosal immunity is generated in addition to systemic immunity.
Vaccines that can produce mucosal immunity are known. These vaccines are basically administered by the nasal or oral route. They present the unique advantage of inducing protective immune responses at mucosal and systemic levels. They also target the passage of mucous membranes blocking the pathways of most bacterial and viral pathogens (blocking crossing). For example, this is applied by nasal spraysInfluenza vaccine orEven in the case of orally administered polio vaccines.
Influenza virus (alphavirus) vaccination by ocular route in ferrets is also described in articles Eyedrop Vaccination Induced Systemic and Mucosal Immunity against Influenza Virus in Ferrets de Sangchul Yoon, eun-Do Kim, min-Suk Song, soo Jung Han, tee Kwann Park, kyou Sub Choi, young-Ki Choi, and Kyoung Yul Seo; PLoS one.2016;11 In (6), e0157634 was studied. The teams of Kyoung Yul Seo, soo Jung Han, hye-Ran Cha, sang-Uk Seo, joo-Hye Song, so-Hyang Chung and Mi-Na Kwen have also studied ocular route vaccination in mice (Eye Mucosa: an Efficient Vaccine Delivery Route for Inducing Protective Immunity; J.Immunol 2010; 185:3610-3619), although mice are not a natural host for viruses. However, no ophthalmic vaccine is currently approved.
In order to vaccinate the global population against various infections caused by at least one pathogen, in particular bacterial or viral infections, there is always a need for more and more effective vaccines. Advantageously, the vaccine must allow the development of immunity known as sterilization.
Effective vaccination is also understood to mean a vaccine administered in the recommended amount and/or correctly at the administration site. Vaccination errors have been found, in particular, due to poor injection sites (e.g. subcutaneous administration of BCG vaccine, which must be administered intradermally), or due to the vaccine dose administered being greater than the recommended dose.
However, to date, there is no method by which the amount of vaccine administered and/or the correct application at the site of administration can be readily verified.
Thus, there is a need for an effective vaccine that can easily ensure good administration, in particular in terms of the amount and/or site of administration.
Disclosure of Invention
The present invention responds to this need with a new vaccination pattern against infections caused by at least one pathogen for (i) enhancing immunity (dual immunity-systemic and mucosal-in fact providing better protection against pathogens for vaccinated hosts and others, as it may limit the risk of pathogen transmission), and (ii) ensuring good administration of the vaccine, both in terms of the amount and/or site of administration.
The present invention thus provides a new inoculation pattern for infections caused by at least one pathogen, more specifically for bacterial and/or viral infections, which is more efficient than other inoculation patterns previously used and which is simple to use.
The invention is used to generate mucosal immunity against at least one pathogen by targeting the ocular mucosa and/or genitourinary mucosa.
The present invention therefore relates to an immunogenic or vaccine composition comprising a marker for the prevention and/or treatment of infections caused by at least one pathogen, characterized in that it is applied to the ocular mucosa and/or to the genitourinary mucosa.
The purpose of administering such a composition is to establish immunity in the mucosa and serum immunity against at least one pathogen. This double immunization serves to better protect the organism from pathogens and limit the risk of infection without subjecting it to severe systemic secondary effects that may occur with some vaccines (e.g., the thrombotic risk observed with some covd-19 vaccines administered intramuscularly). In fact, in the case of the present invention, since serum immunity is indirectly obtained through immunization of mucous membrane, it is expected that no thrombosis accident will occur.
The presence of a marker in the composition is also used to detect and/or verify the amount and/or site of administration, wherein this is done to ensure safe and effective use of the immunogenic or vaccine composition.
According to the present invention, the expression "immunogenic composition" and/or "vaccine composition" is understood to mean a composition that induces an immune response against at least one pathogen after administration to a subject. Vaccine compositions are particularly useful for generating protective and adaptive immune responses against at least one pathogen, more particularly against viruses and/or bacteria. Such immune responses may be humoral and/or cellular.
According to the present invention, the term "marker" is understood to mean any measurable or indicative substance that can be administered in an immunogenic or vaccine composition. Thus, it relates to pharmaceutically acceptable markers. According to a specific embodiment, the marker is used for quantifying and/or visualizing the use of said immunogenic or vaccine composition on the ocular mucosa and/or genitourinary mucosa. More specifically, quantification is understood to mean measuring the amount of an immunogenic or vaccine composition administered. According to one embodiment, the marker is an indicator substance, such as a colorant. As an example, a fluorescein or indocyanine type colorant may be used.
According to the present invention, the expression "infection by at least one pathogen" is understood to mean a disease caused by one or more infectious agents.
According to the present invention, the term "pathogen" is understood to mean any infectious agent capable of causing a disease in its host. More specifically, a pathogen is understood to mean a virus, a bacterium, a parasite, a fungus and/or a prion.
According to the present invention, the expression "virus, bacterium, parasite, fungus and/or prion" is understood to mean a virus, bacterium, parasite, fungus and/or prion which is or can be considered to be a pathogen of the body, preferably of the human body. Thus, this is not generally understood to mean bacteria beneficial to the body, such as probiotics. More specifically, the expression "virus, bacterium, parasite, fungus and/or prion" is thus understood to mean a pathogenic virus, bacterium, parasite, fungus and/or prion.
The expression "infection by at least one pathogen" is understood to mean an infection by pathogenic bacteria and/or viruses and/or parasites and/or fungi and/or prions. According to a specific embodiment, the infection is a bacterial and/or viral infection, and more specifically, the infection is a bacterial or viral infection. For example, the infection is selected from: influenza, herpes, infectious mononucleosis, poliomyelitis, salmonellosis, typhoid or paratyphoid, tuberculosis, cholera, lyme disease, infections caused by staphylococcus aureus (Staphylococcus aureu, in particular methicillin-resistant staphylococcus aureus), infections caused by pneumococci, infections caused by meningococcus, yellow fever, mumps, rotavirus gastroenteritis, measles, rubella, varicella, shingles, viral hepatitis, japanese encephalitis, pertussis, diphtheria, tetanus, infections caused by coronaviruses such as SARS or covd-19, infections caused by human papilloma viruses, prion diseases such as creutzfeldt-jakob disease, infections caused by amoeba such as amoeba disease, syphilis, mycosis, malaria, or infections caused by GNMR (gram negative multi-drug resistant bacteria).
According to the invention, the expression "preventing infection" is understood to mean preventing. Administration of the immunogenic or vaccine composition according to the invention is particularly useful for blocking or reducing the risk of progression of said infection and/or, where applicable, reducing the risk of developing a form of the disease known as severe (meaning having severe symptoms). Administration of the immunogenic or vaccine composition according to the invention may also block or reduce the risk of transmission of pathogens, more specifically viruses or bacteria, typically from one person to another. According to a specific embodiment, the immunogenic or vaccine composition for preventing infection according to the invention is administered to a subject not contaminated with a pathogen, preferably a virus and/or a bacterium, preferably said subject is not infected.
According to the present invention, the expression "treating an infection" is understood to mean a therapy. Administration of an immunogenic or vaccine composition according to the invention may in fact be considered to stimulate the natural defenses of the body even though the human has been minimally (minis) contaminated with pathogens, preferably viruses and/or bacteria. According to a specific embodiment, the immunogenic or vaccine composition for treating an infection according to the invention is administered to a subject contaminated and/or infected with a pathogen, preferably a virus and/or a bacterium.
Thus, preferably, the present invention relates to an immunogenic or vaccine composition comprising a marker for preventing infections caused by at least one pathogen, in particular bacterial and/or viral infections, characterized in that it is applied to the ocular mucosa and/or to the genitourinary mucosa. According to one embodiment, the invention thus relates to an immunogenic or vaccine composition comprising a marker for the treatment of bacterial infections, characterized in that it is applied to the ocular mucosa and/or to the genitourinary mucosa. Thus, according to another embodiment, the present invention relates to an immunogenic or vaccine composition comprising a marker for the prevention of viral infections, characterized in that it is applied to the ocular mucosa and/or to the genitourinary mucosa.
According to the invention, the expression "ocular mucosa" is understood to mean conjunctiva and cornea. The conjunctiva is a transparent mucosa that covers the inner surfaces of the upper and lower eyelids and covers the anterior surface of the eyeball. Thus, ocular mucosa is more precisely understood to mean the palpebral conjunctiva and bulbar conjunctiva, as well as the conjunctival fornix.
According to the invention, the expression "genitourinary mucosa" is understood to mean the mucosa of the urinary and/or reproductive system (male and female systems). Thus, rather, the urogenital mucosa is understood to mean the urogenital tract.
Targeting of the ocular and/or genitourinary mucosa serves to target the mucosa, which (i) is itself only weakly involved in the transmission of pathogens, but (ii) at the same time has very high immunological activity, which serves to immunize the body very rapidly, in particular prior to respiratory tract infections. This embodiment also serves to reduce the potential risk of serious side effects associated with vaccination.
One of the non-limiting assumptions of the present inventors is the fact that infection of the eye by pathogens leads to a rapid build up of immunity, so that the body wins time, and thus is immunized when contamination and/or infection progresses in the body, in particular through the nose. This progression of contamination and/or infection from eye to nose can be explained by the presence of the nasolacrimal duct connecting the nose and eyes. In the case of viral-induced keratitis (epidemic keratitis type), nasolacrimal duct infection has been described. The typical progression of this disease begins with infection of the conjunctiva by droplets and appears as severe conjunctivitis followed by pharyngitis. This can also explain why subjects, particularly medical personnel, develop systemic immunity against SARS-CoV-2 after onset of conjunctivitis positive for SARS-CoV-2.
Preferably, the immunogenic or vaccine composition is applied to the ocular mucosa. Thus, according to one embodiment, the present invention relates to an immunogenic or vaccine composition comprising a marker for use in the prevention and/or treatment of a bacterial infection, characterized in that it is applied to the ocular mucosa. Thus, according to another embodiment, the present invention relates to an immunogenic or vaccine composition comprising a marker for use in the prevention and/or treatment of viral infections, characterized in that it is applied to the ocular mucosa.
Thus, according to another even more preferred embodiment, the present invention relates to an immunogenic or vaccine composition comprising a marker for the prevention of bacterial infections, characterized in that it is applied to the ocular mucosa. Thus, according to another even more preferred embodiment, the present invention relates to an immunogenic or vaccine composition comprising a marker for the prevention of viral infections, characterized in that it is applied to the ocular mucosa.
According to the invention, the immunogenic or vaccine composition may be administered in only one eye or in both eyes. Unlike intramuscular, subcutaneous or intradermal administration of vaccines, which require increased organization and medical work (e.g., preparation of syringes, need available resuscitation equipment in the case of severe reactions to vaccination, etc.), injection onto the ocular mucosa (typically by eye drops) is simpler and faster to perform. In fact, the serious risks (such as the above-mentioned risk of thrombosis) are reduced, as are the risks of serious allergies, which are mainly manifested as stinging, tearing or even redeye eyes. Vaccination via eye drops can be further used for faster and larger scale vaccination.
According to one embodiment, the immunogenic or vaccine composition comprises one or more substances for eliciting an immune response against one or more pathogens, in particular substances for eliciting an immune response against one or more viruses and/or one or more bacteria. Typically, the immunogenic or vaccine composition according to the invention comprises one or more antigens of the pathogen, in particular one or more antigens of the virus or the bacterium. Preferably, the antigen is specific for the pathogen causing the infection, in particular the virus or bacteria causing the infection.
According to one embodiment, once the immunization or vaccine composition comprises at least one antigen of said pathogen, a microorganism (e.g. virus or bacterium) producing at least one antigen of said pathogen, or it comprises genetic material (typically mRNA) necessary for expression of at least one antigen of said pathogen, for eliciting an immune response against at least one pathogen (in particular virus and/or bacterium). In the first case the antigen will be in direct contact with the mucosa after administration, while in the second and third cases latency, i.e. the time to antigen production after administration of the composition, can be expected. Preferably, the microorganism itself (per se) is not pathogenic, and the only immune response that can be elicited is an immune response associated with the antigen of the pathogen.
According to a specific embodiment, the substance/antigen for eliciting an immune response against said pathogen is selected from the group consisting of: (i) inactivated virus, (ii) inactivated bacteria or bacterial toxins, (iii) attenuated viruses, (iv) attenuated bacteria or bacterial toxins, (V) attenuated or inactivated parasites, (vi) attenuated or inactivated fungi or mycotoxins, (vii) prions, (viii) genetically modified microorganisms (expressing or being able to express at least one antigen of a pathogen, optionally inactivated or attenuated), (ix) messenger ribonucleic acids (mRNA) encoding one or more antigens (e.g. virus or bacterial proteins) of a virus or bacteria or parasite or fungi, (X) deoxyribonucleic acids (DNA) encoding one or several antigens (e.g. virus or bacterial proteins) of a virus or bacteria or parasite or fungi, (xi) virus or parasite or mycoproteins or one or more fragments thereof, or (xii) fusion proteins comprising a virus and/or a bacterium and/or a parasite and/or a fungus and/or prion protein or one or more fragments thereof also (ii) substances/antigens for eliciting an immune response against said pathogen may be (per se) themselves, (X) encoding one or more antigens (e.g. virus or bacterial proteins) of a pathogen, in particular a plasmid or a non-expressing one or more antigens of a recombinant pathogen (e.g. a dendritic cell or a virus) or a recombinant protein, or (xvi) a pseudoviral particle comprising one or more antigens of a pathogen. Fragments of viral and/or bacterial and/or parasitic and/or fungal and/or prion proteins, which preferably contain an immunodominant epitope or a biological analogue thereof. According to one embodiment, the fragment of the protein is an immunogenic fragment. The fragment and the protein may be recombinant.
According to one embodiment, genetically modified microorganism is understood to mean a microorganism (preferably inactivated or attenuated) expressing or being able to express one or more antigens (e.g. viral or bacterial proteins) of a virus or a bacterium or a parasite or a fungus, or a microorganism (in particular a virus, a bacterium or a parasite) which has been genetically modified not to infect a host organism (e.g. by blocking their penetration through a target cell or blocking their proliferation). For example, it may relate to a viral vector type adenovirus.
According to a specific embodiment, the substance/antigen for eliciting an immune response against said virus and/or said bacterium is selected from the group consisting of: (i) inactivating a virus, (ii) inactivating a bacterium or bacterial toxin, (iii) attenuating a virus, (iv) attenuating a bacterium or bacterial toxin, (V) genetically modified microorganisms (preferably inactivated or attenuated) expressing or capable of expressing one or more antigens of a virus or bacterium (such as a virus or bacterial protein), (vi) messenger ribonucleic acids (mRNA) encoding one or more antigens of a virus or bacterium (such as a virus or bacterial protein), (vii) deoxyribonucleic acids (DNA) encoding one or more antigens of a virus or bacterium (such as a virus or bacterial protein), (viii) a virus or bacterial protein or one or more fragments thereof, or (ix) fusion proteins comprising a virus and/or bacterial protein, or one or more fragments thereof.
The composition according to the invention may comprise one or more substances (antigens) for eliciting an immune response against one or more pathogens, in particular against one or more viruses, against one or more bacteria, or against one or more viruses and one or more bacteria. According to one embodiment, the various substances (antigens) may be directed against different parts of the same virus or the same bacterium or the same fungus or the same parasite (e.g. different epitopes on viral or bacterial proteins); different strains of the same virus or the same bacterium or the same fungus; variants of the same virus or the same bacterium or the same fungus or the same parasite; or even several different viruses and/or several different bacteria and/or different fungi and/or different parasites (combination vaccine). Thus, the immunogenic or vaccine compositions of the invention may be monovalent or multivalent. Monovalent immunogenic or vaccine compositions provide protection against a single pathogen, while multivalent immunogenic or vaccine compositions provide protection against several pathogens.
According to one embodiment, the expression "viral or bacterial or fungal or parasitic proteins" is understood to mean more specifically structural and auxiliary proteins of the virus, or proteins involved in the adhesion, attachment, invasion and/or internalization of bacteria in body cells, or proteins involved in the adhesion, attachment and/or invasion of fungi in tissues, or proteins involved in the adhesion, attachment, invasion and/or internalization of parasites in biological cells (such as erythrocytes), or even as applicable proteins secreted by viruses, bacteria, fungi and/or parasites. Preferably, the viral, bacterial, fungal or parasitic protein is selected from: envelope proteins, matrix proteins, membrane proteins or transmembrane proteins, surface proteins or toxoids. For example, the bacterial or fungal surface protein may be an adhesin and the viral envelope protein may be a spike protein.
According to the present invention, a viral protein is understood to mean the natural protein of the virus (viral proteins, such as are found in nature), a mutant protein or a protein which is a variant compared to the natural protein or a synthetic protein (modified, mutated or unmodified mutated).
According to the invention, bacterial proteins are understood to mean the natural proteins of bacteria (bacterial proteins, such as are found in nature), mutant proteins or proteins which are variants compared to the natural proteins or synthetic proteins (modified, mutated or unmodified mutated).
According to the invention, fungal proteins are understood to mean the natural proteins of the fungus (fungal proteins, such as are found in nature), mutant proteins or proteins which are variants compared to the natural proteins or synthetic proteins (modified, mutated or unmodified mutated).
According to the invention, parasite proteins are understood to mean the natural proteins of the parasite (parasite proteins, as found in nature), mutant proteins or proteins which are variants compared to the natural proteins or synthetic proteins (modified, mutated or unmodified mutated).
For example, the pathogens responsible for the targeted infection of the present invention are influenza virus, type 1 or type 2 herpes simplex virus, EB virus, polio virus, salmonella bacteria (preferably Salmonella typhi (Salmonella enterica-typhi) or Salmonella A, B, C) paratyphi A, B, C), mycobacterium (Mycobacterium) bacteria (preferably Mycobacterium tuberculosis (Mycobacterium tuberculosis)), vibrio cholerae @Vibrio cholerae) Bacteria, bacteria belonging to the genus Staphylococcus (preferably Staphylococcus aureus (Staphylococcus aureus)), pneumococci, meningococcus, yellow fever virus, mumps virus, rotavirus, measles virus, rubella virus, varicella or herpes zoster virus, viruses known as hepatitis A, hepatitis B, hepatitis C, hepatitis B and hepatitis E, japanese encephalitis virus, bode's bacteriaBordetella) Bacteria of the genus (preferably bordetella pertussisBordetella pertussis) And bordetella parapertussisBordetella parapertussis) Bacteria of the genus Corynebacterium, preferably diphtheria (C. Diphtheria), ulcer (C. Ulcerans), pseudotuberculosis (C. Pseudotuberculosis), clostridium tetani (Clostridium tetani) bacteria, coronaviruses such as SARS-CoV or SARS-CoV-2 or human papilloma viruses, bacteria of the spirochete family, in particular borrelia burgdorferi (Borrelia burgdorferi) or treponema pallidum (Treponema pallidum).
An immunogenic or vaccine composition according to the invention is administered to a subject. According to one embodiment, the immunogenic or vaccine composition is for use in the prevention and/or treatment of an infection in a human caused by at least one pathogen. According to the invention, the person may be an infant, a child or an adult.
According to another embodiment, veterinary use of the immunogenic or vaccine composition according to the invention is conceivable. In this case, the subject is an animal.
According to one embodiment, the immunogenic or vaccine composition is administered to the subject in an immunologically effective amount. Such amounts may be determined by the practitioner. The expression "immunologically effective amount" is understood to mean a sufficient amount to be effective for prophylaxis and/or treatment, in particular in a subject in need of such prophylaxis or such treatment.
According to one embodiment, the marker is present in the immunogenic or vaccine composition in an amount sufficient to detect/visualize it.
According to one embodiment, the immunogenic composition or vaccine composition is administered to a subject that has not been contaminated or even infected by a pathogen (in particular a virus and/or a bacterium) that causes an infection, or to a subject that has been contaminated or even infected by a pathogen (in particular a virus and/or a bacterium) that causes an infection, which may have developed symptoms (mild or severe) or no symptoms.
According to one embodiment, the immunogenic or vaccine composition is administered once or several times, preferably once, twice or three times, on the ocular mucosa and/or genitourinary mucosa. According to a specific embodiment, the immunogenic or vaccine composition is administered at least twice (in other words, two doses of the immunogenic or vaccine composition are administered) on the ocular mucosa and/or genitourinary mucosa. According to a specific embodiment, when the immunogenic or vaccine composition is administered several times, it targets the same mucosa: for example, two or three times on the ocular mucosa, or two or three times on the genitourinary mucosa. The length of time between the first and other subsequent administrations is variable depending on the pathogen targeted, e.g., several weeks for an immunogenic composition against the SARS-CoV-2 virus, or several months for an immunogenic composition against hepatitis A. According to one embodiment, the immunogenic or vaccine composition is applied to the ocular mucosa and/or genitourinary mucosa before or after at least one administration of the immunogenic or vaccine composition against the same pathogen by a different mode of administration, for example by intranasal or intradermal routes. For example, the immunogenic or vaccine composition is applied to the ocular mucosa after a first intramuscular administration (here the first vaccination, then the first subsequent dose).
According to one embodiment, the immunogenic or vaccine composition is administered as drops, lyophilisates or other dry forms. According to one embodiment, the immunogenic or vaccine composition may also be administered as a dry, powder, gel, nanoparticle or pomade composition (pomade composition). Typically, when administered in the form of drops, it means that the immunogenic or vaccine composition is a liquid formulation, and when administered in the form of a lyophilisate or a dry composition, the immunogenic or vaccine composition is in the form of a powder. The powder may be applied directly to the mucosa or on filter paper, polymers, gels, nanoparticles or mucosa or any other suitable substance support that will be in contact with the ocular mucosa and/or genitourinary mucosa. Thus, the immunogenic or vaccine composition will be transferred from the filter paper, polymer, gel or any other suitable substance or support to the ocular mucosa and/or genitourinary mucosa. The dried composition may be obtained after freezing the immunogenic or vaccine composition according to the invention, followed by drying with any suitable technique (except for freeze-drying, which is used to obtain a lyophilisate).
According to one embodiment, the immunogenic or vaccine composition is administered by using an applicator. The applicator is particularly useful for facilitating the administration of the composition, for example it facilitates infusion of drops (dropper) or powders, lyophilisates. The applicator may also be an ampoule, syringe, filter paper (with e.g. fluid or lyophilisate), dropper bottle, single dose applicator, vaginal spiral or sponge applicator, or even a fabric, a tampon comprising a modified outer surface (i.e. the surface comprises one or more substances for eliciting an immune response against SARS-CoV-2, such as proteins, viral vectors, etc.), or a condom comprising a modified outer surface, etc.
According to one embodiment, the immunogenic or vaccine composition comprises or consists of one or more substances (antigens) for eliciting an immune response against a pathogen, in particular a virus and/or a bacterium. According to one embodiment, the immunogenic composition according to the invention may be considered to be comprised in a vaccine composition (vaccine). The term "vaccine" or "vaccine against the pathogen causing the infection" may also be used instead of the expression "vaccine composition". For example, when the virus is SARS-CoV-2, the immunogenic or vaccine composition according to the invention may be an mRNA vaccine of Pfizer/BioNTech (commonly referred to as Bntl62b2 or) Or non-replicating viral vector vaccines from aliskiren (commonly referred to as) An Alaslicon ChAdOxl-S or a COVID-19 vaccine. When the bacterium is Vibrio cholerae, the immunogenic composition or vaccine composition according to the invention may be +.>Vaccine, or also +.>Vaccines (combination vaccine against diphtheria, clostridium tetani, tetanus and polio).
According to a preferred embodiment, the vaccine composition comprises an adjuvant and/or excipient.
According to one embodiment, the immunogenic or vaccine composition comprises a pharmaceutically acceptable vehicle (vehicle).
The adjuvants and/or excipients and/or diluents and/or pharmaceutically acceptable vehicles are those conventionally used. For example, the pharmaceutically acceptable vehicle may be a solvent or solution for diluting the composition prior to administration by ocular route or administration on the genitourinary mucosa.
According to one embodiment, the immunogenic or vaccine composition according to the invention may further comprise one or more additional substances. Preferably, the further substance is selected from:
the presence of a preservative agent(s),
-a surfactant, and
-an additive.
For example, the preservative may be an antimicrobial preservative, the purpose of which is to prevent microbial contamination of the immunogenic or vaccine composition. According to the invention, the preservative is a mucosa-compatible preservative.
In order to obtain a higher antigenicity and thus a greater immune response, substances such as surfactants may be added to the immunogenic or vaccine composition to extend the exposure time on the ocular and/or genitourinary mucosa and possibly to enable calculation of the exposure time of the composition on the mucosa.
Other substances, such as additives, may be added to impart advantageous properties to the immunogenic or vaccine composition, such as substances that improve the immunogenicity or the permeability of the vaccine composition in the mucosa, or substances for extending the contact time between the mucosa and the composition (e.g. hyaluronic acid, one or more polymers for forming hydrogels (e.g. carbomers), cellulose derivatives, etc.).
The invention also relates to a method for preventing and/or treating an infection caused by at least one pathogen in a subject comprising administering an immunogenic or vaccine composition on the ocular mucosa and/or genitourinary mucosa. More particularly, the present invention relates to a method for inducing a protective immune response against at least one pathogen, in particular a virus and/or a bacterium, comprising administering an immunogenic or vaccine composition on the ocular mucosa and/or the genitourinary mucosa.
The invention also relates to the use of an immunogenic or vaccine composition against at least one pathogen, in particular a virus and/or a bacterium, for the preparation of a medicament intended for the prevention and/or treatment of infections caused by at least one pathogen, and wherein said medicament is intended for administration to the ocular and/or genitourinary mucosa.
Drawings
Fig. 1 shows the results of hamster group 1.
Fig. 2 shows the results of hamster group 2.
Figure 3 shows the average weights of hamsters in the four groups tested in example 5.
Detailed Description
Examples
Example 1: examples of liquid compositions
Table 1 below summarizes the compositions according to the present invention that may be used.
TABLE 1: liquid composition
Example 2: examples of freeze-dried compositions table 2 below summarizes compositions according to the invention that may be used.
TABLE 2: freeze-dried composition
Example 3: immunization of hamsters against SARS-CoV-2 by ocular route
Hamsters have ACE2 receptors. Thus, they may be contaminated and diseased with SARS-CoV-2.
1. Comparison of two hamsters after two injections of virus
Two groups of hamsters were studied.
In group 1, 3X 10 6 The individual SARS-CoV-2 viruses (strain b.1.214) contaminated n=7 hamsters by nasal injection and contained 3×10 in group 2 6 Eye drops of the individual SARS-CoV-2 viruses (strain b.1.214) pollute n=7 hamsters. A coloring type marker may be added to the eye drops.
During observation, hamsters of group 1 were ill, identifiable by significant weight loss, while hamsters of group 2 were not ill.
Indeed, as can be seen in fig. 1, hamsters of group 1 begin to lighten from day 2, with the greatest lightening on day 5 and return to normal on day 12; this indicates that hamsters became ill after contamination/infection by nasal injection of SARS-CoV-2. In contrast, as can be seen in figure 2, group 2 hamsters did not lose weight after inoculation of SARS-CoV-2 by the ocular route. This indicates that these animals maintained good health.
After 14 days, both groups were again exposed to a solution containing 3×10 6 Nasal injection of individual doses of SARS-CoV-2 virus.
In both groups, hamster body weight was continuously increased (see figures 1 and 2). More specifically, on day 21, animals of group 1 did not become ill again after inhalation of the second dose of SARS-CoV-2 virus. This means that they have acquired immunity due to the disease that developed during the first 10 days of the experiment.
Furthermore, on day 21, hamsters of group 2 were not ill after inhalation of the second dose of SARS-CoV-2 virus. This means that hamsters were immunized as SARS-CoV-2 was first applied by ocular route.
Thus, hamsters of group 2 acquired immunity by periocular (epi-ocular) application, unlike group 1, which was obtained without developing severe systemic disease.
2. Study of hamsters after injection of viruses by ocular route
In addition, the eye route is accepted to contain 3×10 6 N=10 for a single application (possible presence of a colored marker) of a composition of individual SARS-CoV-2 virus dosesOnly other hamster studies showed that they produced high yields of antiviral neutralizing antibodies (at least 1640 in serum). These results suggest that hamsters did not develop disease by periocular application of the virus and that immunity against SARS-CoV-2 was obtained that was detectable in serum.
Example 4: research of the spread of SARS-CoV-2 during nasal infection
The inventors analyzed the transmission of the virus in hamsters contaminated with SARS-CoV-2 by nasal injection, as described in example 3.
Thus, the inventors observed that during the first 48 hours after virus entry into the nose, the infection progressed slowly, with nasal infection only in the mucosa, forming an aerosol. These aerosols can then infect bronchi and alveoli, especially during inspiration, and contaminate others during expiration.
Example 5: vaccination by different immunogenic or vaccine compositions
Four new groups of hamsters were studied.
In group 1, at d=1, 20 μl of the vaccine containing the Janssen/Johnson & Johnson non-replicating viral vector (commonly referred to as ad26cov2. S) directly removed from the vial (without any modification) was administered to the left eye of n=8 hamsters. After 14 days (d=14), 20 μl of the same vaccine, which was directly removed from the vial (without any modification), was reapplied to the left eye of n=8 hamsters.
In group 2, at d=1, 50 μl of the vaccine containing the Janssen/Johnson non-replicating viral vector (commonly referred to as ad26cov2. S) directly removed from the vial (without any modification) was administered intramuscularly to the bilateral buttocks of n=8 hamsters. After 14 days (d=14), 50 μl of the same vaccine, taken directly from the vial (without any modification), was again administered intramuscularly to the bilateral buttocks of n=8 hamsters.
In group 3, 20 μl PBS (phosphate buffered saline) was administered in the left eye of n=8 hamsters on day d=1. After 14 days (d=14), 20 μl PBS (phosphate buffered saline) was again administered in the left eye of n=8 hamsters.
In group 4, inDay 14 of the experiment (d=14), 20 μl containing 3×10 was administered in both eyes of n=8 hamsters 6 Solutions of individual SARS-CoV-2 viruses (variants of SARS-CoV-2 virus) (attenuated viruses, but not inactivated viruses).
After a further 14 days (d=28 since the start of the experiment), 200 μl of the composition containing 6×10 6 A solution of TCID 50 (tissue culture infectious dose 50) SARS-CoV-2 virus (variant of SARS-CoV-2 virus) was used to intranasally contaminate animals in group 4.
Markers may be added to the administered vaccines and solutions in order to quantify and/or visualize their use.
Weight loss (i.e., an indicator of hamster illness) was analyzed for animals in each of the four groups. The results are shown in fig. 3. The curves show the average weights of hamsters in the four groups.
The results show that unlike hamsters of group 3, hamsters of groups 1, 2 and 4 are protected and not diseased.
Claims (15)
1. An immunogenic or vaccine composition comprising a marker for use in the prevention and/or treatment of an infection caused by at least one pathogen, characterized in that it is applied to the ocular mucosa and/or genitourinary mucosa.
2. The immunogenic or vaccine composition of claim 1, wherein it is administered to the ocular mucosa.
3. The immunogenic or vaccine composition according to any preceding claim, wherein the marker is used to quantify and/or visualise the use of the immunogenic or vaccine composition on ocular mucosa and/or genitourinary mucosa.
4. The immunogenic or vaccine composition according to any one of the preceding claims, characterized in that the marker is a colorant.
5. The immunogenic or vaccine composition according to any one of the preceding claims, characterized in that the infection is a bacterial and/or viral infection.
6. An immunogenic or vaccine composition according to any preceding claim, characterised in that the composition comprises one or more substances for eliciting an immune response against one or more pathogens.
7. The immunogenic or vaccine composition according to any one of the preceding claims, characterized in that the pathogen is selected from the group consisting of: viruses, bacteria, parasites, fungi and/or prions, in particular viruses and/or one or more bacteria.
8. An immunogenic or vaccine composition according to claim 6, characterized in that the substance for eliciting an immune response is selected from the group consisting of: an inactivated virus, an inactivated bacterium or bacterial toxin, an attenuated virus, an attenuated bacterium or bacterial toxin, an attenuated or inactivated parasite, an attenuated or inactivated fungus or fungal toxin, a prion, a microorganism genetically modified by a bacterium, parasite or fungus, a messenger ribonucleic acid (mRNA) encoding one or more antigens of a virus or bacterium or parasite or fungus, a deoxyribonucleic acid (DNA) encoding one or more antigens of a virus or bacterium or parasite or fungus, or one or more fragments thereof, fusion proteins or one or more fragments thereof comprising a virus and/or bacterium and/or parasite and/or fungus and/or prion protein, a pathogen, a recombinant cell expressing or capable of expressing one or more antigens of a pathogen, a DNA plasmid encoding one or more antigens of a pathogen, or a pseudoviral particle comprising one or more antigens of a pathogen.
9. The immunogenic or vaccine composition of claim 8, wherein the viral, bacterial, parasitic, or fungal protein is selected from the group consisting of: envelope proteins, matrix proteins, membrane proteins or transmembrane proteins, surface proteins or toxoids.
10. The immunogenic or vaccine composition according to any one of the preceding claims, characterized in that it is administered in the form of drops, lyophilisates, dry compositions, powders, gels, nanoparticles or pomades.
11. The immunogenic or vaccine composition according to any one of the preceding claims, characterized in that it is administered by using an applicator.
12. The immunogenic or vaccine composition according to any one of the preceding claims for use in the prevention and/or treatment of an infection caused by at least one pathogen selected from the group consisting of: influenza, herpes, infectious mononucleosis, lyme disease, poliomyelitis, salmonellosis, typhoid or paratyphoid, tuberculosis, cholera, infections caused by staphylococcus aureus, infections caused by pneumococci, infections caused by meningococcus, yellow fever, mumps, rotavirus gastroenteritis, measles, rubella, varicella, shingles, hepatitis, japanese encephalitis, pertussis, diphtheria, tetanus, infections caused by coronaviruses, infections caused by human papillomaviruses, prion diseases, infections caused by amoeba, such as syphilis, mycosis, malaria, or infections caused by GNMR bacteria.
13. The immunogenic or vaccine composition according to any one of the preceding claims for use in the prevention and/or treatment of an infection caused by at least one pathogen in a human or animal.
14. The immunogenic composition or vaccine composition according to any one of the preceding claims, characterized in that it further comprises one or more additional substances.
15. An immunogenic or vaccine composition according to claim 14, characterised in that the further substance is selected from:
the presence of a preservative agent(s),
-a surfactant, and
-an additive.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102021001467.7 | 2021-03-22 | ||
| EP21180477.8 | 2021-06-18 | ||
| EP21180477.8A EP4062931A1 (en) | 2021-03-22 | 2021-06-18 | New application of an immunogenic or vaccine composition |
| PCT/EP2022/057549 WO2022200385A1 (en) | 2021-03-22 | 2022-03-22 | Novel use of an immunogenic or vaccinal composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116669703A true CN116669703A (en) | 2023-08-29 |
Family
ID=87726486
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202280007011.5A Pending CN116669703A (en) | 2021-03-22 | 2022-03-22 | New use of immunogenic or vaccine compositions |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116669703A (en) |
-
2022
- 2022-03-22 CN CN202280007011.5A patent/CN116669703A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11000585B2 (en) | Composition comprising antigens and a mucosal adjuvant and a method for using | |
| ES2283452T3 (en) | BACTERINE BASED IMPROVED VACUANA OF I MYCOPLASMA HYOPNEUMONIAE / I. | |
| US20020068090A1 (en) | Calcium phosphate particles as mucosal adjuvants | |
| JP2004536106A (en) | Mycoplasma bovis vaccine and method for reducing pneumonia in animals | |
| Gogev et al. | Glycol chitosan improves the efficacy of intranasally administrated replication defective human adenovirus type 5 expressing glycoprotein D of bovine herpesvirus 1 | |
| EP3549600A1 (en) | A vaccine for protection against streptococcus suis | |
| CN101123982B (en) | Lipid and nitrous oxide combination as adjuvant for the enhancement of the efficacy of vaccines | |
| US20230390376A1 (en) | Vaccine for protection against streptococcus suis | |
| EP3661546B1 (en) | A vaccine for protection against streptococcus suis | |
| US9585954B2 (en) | Mucosal immunization | |
| ES2937136T3 (en) | IgM protease antigen vaccine to protect against Streptococcus suis | |
| CN116669703A (en) | New use of immunogenic or vaccine compositions | |
| AU2022246020A1 (en) | New application of an immunogenic or vaccine composition | |
| JPH05155782A (en) | Vaccine for horse rhinopneumonitis | |
| CN116568322A (en) | New use of an immunogenic or vaccine composition against covd-19 | |
| US20240165219A1 (en) | Application of an Immunogenic or Vaccine Composition Against COVID-19 | |
| RU2809375C1 (en) | WHOLE VIRION INACTIVATED VACCINE AGAINST SARS-Cov-2 INFECTION AND ITS USE | |
| Plotkin | Vaccines in the 21st century | |
| EP1594537B1 (en) | Vaccination or immunization using a prime-boost regimen against brsv, bhv-1, bvdv, bpi-3 | |
| EP3454893A1 (en) | A composition comprising antigens and a mucosal adjuvant and a method for using | |
| Bowersock et al. | Vaccine Delivery Systems | |
| Portilho et al. | Different Platforms, Immune Response Modulators and Challenges in SARS-CoV-2 Vaccination | |
| KR20140046143A (en) | A novel adjuvant of vaccine for eye-drop vaccination | |
| US20220339276A1 (en) | A vaccine for protection against streptococcus suis | |
| CN117224663A (en) | Vaccine composition of porcine pseudorabies virus subunit, and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |