BR102022005518A2 - SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS ANTIGEN POLYPEPTIDE PROCESS AND ITS APPLICATION - Google Patents
SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS ANTIGEN POLYPEPTIDE PROCESS AND ITS APPLICATION Download PDFInfo
- Publication number
- BR102022005518A2 BR102022005518A2 BR102022005518-1A BR102022005518A BR102022005518A2 BR 102022005518 A2 BR102022005518 A2 BR 102022005518A2 BR 102022005518 A BR102022005518 A BR 102022005518A BR 102022005518 A2 BR102022005518 A2 BR 102022005518A2
- Authority
- BR
- Brazil
- Prior art keywords
- application
- acute respiratory
- respiratory syndrome
- severe acute
- syndrome coronavirus
- Prior art date
Links
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 48
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 48
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 36
- 238000000034 method Methods 0.000 title claims abstract description 22
- 230000008569 process Effects 0.000 title claims abstract description 16
- 239000000427 antigen Substances 0.000 title claims abstract description 8
- 102000036639 antigens Human genes 0.000 title claims abstract description 8
- 108091007433 antigens Proteins 0.000 title claims abstract description 8
- 241000315672 SARS coronavirus Species 0.000 title claims abstract 13
- 230000000890 antigenic effect Effects 0.000 claims abstract description 14
- 208000025721 COVID-19 Diseases 0.000 claims abstract description 12
- 238000011282 treatment Methods 0.000 claims abstract description 10
- 238000003745 diagnosis Methods 0.000 claims abstract description 8
- 208000035473 Communicable disease Diseases 0.000 claims abstract description 7
- 239000003814 drug Substances 0.000 claims abstract description 6
- 238000002360 preparation method Methods 0.000 claims abstract description 5
- 229960005486 vaccine Drugs 0.000 claims abstract description 5
- 238000001514 detection method Methods 0.000 claims abstract description 3
- 229940079593 drug Drugs 0.000 claims abstract 2
- 241001678559 COVID-19 virus Species 0.000 claims description 16
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 239000000243 solution Substances 0.000 claims description 6
- 238000012360 testing method Methods 0.000 claims description 6
- 230000001900 immune effect Effects 0.000 claims description 4
- 230000028993 immune response Effects 0.000 claims description 3
- 239000000839 emulsion Substances 0.000 claims description 2
- 239000002502 liposome Substances 0.000 claims description 2
- 238000002965 ELISA Methods 0.000 claims 2
- 102000014914 Carrier Proteins Human genes 0.000 claims 1
- 108010078791 Carrier Proteins Proteins 0.000 claims 1
- 238000007792 addition Methods 0.000 claims 1
- 125000000539 amino acid group Chemical group 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- 239000002775 capsule Substances 0.000 claims 1
- 239000006071 cream Substances 0.000 claims 1
- 238000012217 deletion Methods 0.000 claims 1
- 230000037430 deletion Effects 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- 239000000499 gel Substances 0.000 claims 1
- 230000002519 immonomodulatory effect Effects 0.000 claims 1
- 239000007943 implant Substances 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 claims 1
- 239000006210 lotion Substances 0.000 claims 1
- 239000004530 micro-emulsion Substances 0.000 claims 1
- 239000003094 microcapsule Substances 0.000 claims 1
- 239000004005 microsphere Substances 0.000 claims 1
- 239000002088 nanocapsule Substances 0.000 claims 1
- 239000007908 nanoemulsion Substances 0.000 claims 1
- 239000002077 nanosphere Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 238000007920 subcutaneous administration Methods 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 claims 1
- 229940031626 subunit vaccine Drugs 0.000 claims 1
- 239000000725 suspension Substances 0.000 claims 1
- 239000003826 tablet Substances 0.000 claims 1
- 229940023147 viral vector vaccine Drugs 0.000 claims 1
- 241000711573 Coronaviridae Species 0.000 abstract description 15
- 241000700605 Viruses Species 0.000 abstract description 5
- 230000003472 neutralizing effect Effects 0.000 abstract description 3
- 239000002671 adjuvant Substances 0.000 description 10
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 230000003612 virological effect Effects 0.000 description 4
- 229940096437 Protein S Drugs 0.000 description 3
- 101710198474 Spike protein Proteins 0.000 description 3
- 230000000840 anti-viral effect Effects 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 231100000517 death Toxicity 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000000241 respiratory effect Effects 0.000 description 3
- 238000002255 vaccination Methods 0.000 description 3
- 239000007762 w/o emulsion Substances 0.000 description 3
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 2
- 102100035765 Angiotensin-converting enzyme 2 Human genes 0.000 description 2
- 108090000975 Angiotensin-converting enzyme 2 Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000638154 Homo sapiens Transmembrane protease serine 2 Proteins 0.000 description 2
- -1 MPL and QS -21) Substances 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 208000037847 SARS-CoV-2-infection Diseases 0.000 description 2
- 101710172711 Structural protein Proteins 0.000 description 2
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 2
- 102100031989 Transmembrane protease serine 2 Human genes 0.000 description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- 125000003275 alpha amino acid group Chemical group 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000009260 cross reactivity Effects 0.000 description 2
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 239000012678 infectious agent Substances 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 229940031439 squalene Drugs 0.000 description 2
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- 241000008904 Betacoronavirus Species 0.000 description 1
- 229940022962 COVID-19 vaccine Drugs 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 208000001528 Coronaviridae Infections Diseases 0.000 description 1
- 108010061994 Coronavirus Spike Glycoprotein Proteins 0.000 description 1
- 102100038132 Endogenous retrovirus group K member 6 Pro protein Human genes 0.000 description 1
- 101710091045 Envelope protein Proteins 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 206010022004 Influenza like illness Diseases 0.000 description 1
- 241000127282 Middle East respiratory syndrome-related coronavirus Species 0.000 description 1
- 108090001074 Nucleocapsid Proteins Proteins 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- 201000005702 Pertussis Diseases 0.000 description 1
- 108010064851 Plant Proteins Proteins 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 101710188315 Protein X Proteins 0.000 description 1
- 108091005774 SARS-CoV-2 proteins Proteins 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 206010043376 Tetanus Diseases 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 108050008392 Viral spike glycoproteins Proteins 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
- DIZPMCHEQGEION-UHFFFAOYSA-H aluminium sulfate (anhydrous) Chemical compound [Al+3].[Al+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O DIZPMCHEQGEION-UHFFFAOYSA-H 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000037029 cross reaction Effects 0.000 description 1
- 229960003983 diphtheria toxoid Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000008975 immunomodulatory function Effects 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 238000000126 in silico method Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000007918 pathogenicity Effects 0.000 description 1
- 235000021118 plant-derived protein Nutrition 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 230000036647 reaction Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000000405 serological effect Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000007502 viral entry Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 244000052613 viral pathogen Species 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Landscapes
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
processo de polipeptídeo antigênico de coronavírus da síndrome respiratória aguda grave e sua aplicação. a invenção se refere ao processo caracterizado por peptídeos antigênicos de coronavírus e sua aplicação. especificamente, a invenção se refere a um polipeptídio do vírus sars- cov-2 (seq id no: 1) visando à aplicação deste no preparo de potencial vacinal contra a doença covid-19 e outras doenças infecciosas associadas, além da preparação de insumo para diagnóstico por detecção de sars-cov-2, ou preparação de medicamentos para o tratamento como antígeno de ligação a anticorpo neutralizante, tanto na medicina humana quanto veterinária.severe acute respiratory syndrome coronavirus antigenic polypeptide process and its application. The invention refers to the process characterized by coronavirus antigenic peptides and their application. specifically, the invention refers to a polypeptide from the sarscov-2 virus (seq id no: 1) aiming at its application in the preparation of vaccine potential against the covid-19 disease and other associated infectious diseases, in addition to the preparation of input for diagnosis by detection of sars-cov-2, or preparation of medicines for treatment as a neutralizing antibody-binding antigen, both in human and veterinary medicine.
Description
[001] A presente invenção trata de processo caracterizado pela utilização de polipeptídeos de SARS-CoV-2 com características antigênicas para a prevenção, diagnóstico ou tratamento da doença COVID-19 e doenças infecciosas respiratórias associadas, visando sua aplicação tanto na medicina humana quanto veterinária.[001] The present invention deals with a process characterized by the use of SARS-CoV-2 polypeptides with antigenic characteristics for the prevention, diagnosis or treatment of COVID-19 disease and associated respiratory infectious diseases, aiming for their application in both human and veterinary medicine .
[002] O Brasil tem uma das epidemias causadas pelo coronavírus 2 da síndrome respiratória aguda grave (SARS-CoV-2), de mais rápido crescimento no mundo. Devido aos limitados dados disponíveis como as avaliações do impacto de intervenções não farmacêuticas e testagem na população, além da vacinação com as vacinas existentes terem quantidade limitada para a população, são grandes os esforços no desafio do controle da disseminação viral. O coronavírus SARS-CoV-2 é um novo betacoronavírus com um genoma de s 30 kb que foi relatado pela primeira vez em dezembro de 2019 em Wuhan, China (ASTUTI, 2020; LOBO et al., 2020; MARINHO et al., 2021).[002] Brazil has one of the fastest growing epidemics caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the world. Due to the limited data available, such as assessments of the impact of non-pharmaceutical interventions and testing on the population, in addition to vaccination with existing vaccines having limited quantity for the population, there are great efforts in the challenge of controlling viral spread. The SARS-CoV-2 coronavirus is a new betacoronavirus with a genome of s 30 kb that was first reported in December 2019 in Wuhan, China (ASTUTI, 2020; LOBO et al., 2020; MARINHO et al., 2021 ).
[003] O coronavírus é uma grande família de vírus. Entre eles, coronavírus que transmitem doenças associadas a processo respiratório (como pneumonia e bronquite) como hCoV-229E, hCoV-OC43, hCoV- NL63 e hCoV-HKU1 são relativamente baixos em patogenicidade e persistem na população, distribuídos em várias regiões do mundo, muitas vezes no inverno e início da primavera. Estes coronavírus possuem alguma relação de estado conservado entre motifs de ligação com SARS- CoV-2 (LEE et al. 2020). A importância em se estudar polipeptídeos relacionados ao estado conservado de motifs de ligação é que apresentem reações imunológicas cruzadas e possibilitem gerar resposta imune eficaz contra diversas doenças respiratórias associadas ao SARS- CoV-2. E para teste de anticorpos é necessário que tenha maior especificidade (reatividade cruzada com outros coronavírus) e sensibilidade contra SARS-CoV-2. Devido estas caracteristicas dos kits de detecção de anticorpos (IgM/IgG) em uso necessitarem de reformulações além de garantir uma forma de produção nacional que viabilize custos mais baixos para compra destes kits.[003] Coronavirus is a large family of viruses. Among them, coronaviruses that transmit diseases associated with respiratory processes (such as pneumonia and bronchitis) such as hCoV-229E, hCoV-OC43, hCoV-NL63 and hCoV-HKU1 are relatively low in pathogenicity and persist in the population, distributed in various regions of the world, often in winter and early spring. These coronaviruses have some conserved state relationship between binding motifs with SARS-CoV-2 (LEE et al. 2020). The importance of studying polypeptides related to the conserved state of binding motifs is that they present cross-immunological reactions and make it possible to generate an effective immune response against various respiratory diseases associated with SARS-CoV-2. And for antibody testing, it is necessary to have greater specificity (cross-reactivity with other coronaviruses) and sensitivity against SARS-CoV-2. Due to these characteristics of the antibody detection kits (IgM/IgG) in use, they require reformulation in addition to ensuring a form of national production that enables lower costs for purchasing these kits.
[004] A estrutura genômica de SARS-CoV-2 pode ser dividida em duas regiões, a primeira codificante para proteínas não estruturais e a segunda região codificante para proteínas estruturais como proteína spike (S), proteína do envelope (E), proteína da membrana (M) proteína do nucleocapsídeo (N) e proteínas acessórias, todas elas irão compor a partícula do vírion com capacidade infecciosa em células que expressam em sua superfície o receptor da enzima conversora de angiotensina 2 (ECA2) e a serina protease transmembranar 2 (TMPRSS2), ambas auxiliando na entrada viral (ASTUTI, 2020).[004] The genomic structure of SARS-CoV-2 can be divided into two regions, the first coding for non-structural proteins and the second coding region for structural proteins such as spike protein (S), envelope protein (E), membrane (M), nucleocapsid protein (N) and accessory proteins, all of which will compose the virion particle with infectious capacity in cells that express on their surface the angiotensin-converting enzyme 2 (ACE2) receptor and the transmembrane serine protease 2 ( TMPRSS2), both helping with viral entry (ASTUTI, 2020).
[005] No ano atual de 2021, o número de indivíduos acometidos mundialmente já ultrapassa mais de 175 milhões, por outro lado o número de mortes alcançou a marca dos 4 milhões. No Brasil, já foram mais de 19 milhões de infectados e mais de 540 mil mortes, no dia 18 de julho de 2021 (DONG et al., 2020; BRASIL, 2021).[005] In the current year of 2021, the number of individuals affected worldwide already exceeds more than 175 million, on the other hand, the number of deaths has reached the 4 million mark. In Brazil, there have been more than 19 million infected people and more than 540 thousand deaths, as of July 18, 2021 (DONG et al., 2020; BRASIL, 2021).
[006] O número de infectados/hospitalizados e óbitos esta em queda em países com índices altos de vacinação além de medidas de controle como testagem. Contudo, as possibilidades terapêuticas disponíveis atualmente ainda permanecem escassas, algumas apresentam apenas efeitos parciais (e.g., proteção contra hosptitalização) ou com efeito adverso grave. Outro fator importante é a falta de testes contra COVID-19 devido aos altos custos de importação destes, se faz necessário novas ferramentas de diagnóstico nacional em benefício da saúde pública e no auxílio da vigilância epidemiológica.[006] The number of infected/hospitalized people and deaths is falling in countries with high vaccination rates in addition to control measures such as testing. However, the therapeutic possibilities currently available remain scarce, some only have partial effects (e.g., protection against hospitalization) or serious adverse effects. Another important factor is the lack of tests against COVID-19 due to their high import costs. New national diagnostic tools are necessary for the benefit of public health and to aid epidemiological surveillance.
[007] Na presente invenção, apresentamos um processo caracterizado pela utilização de polipeptídeos antigênicos de coronavírus potencial para prevenção, diagnóstico ou tratamento da doença COVID- 19 e outras doenças infecciosas associadas. Sendo assim, apresentamos uma série de invenções relacionadas ao nosso invento.[007] In the present invention, we present a process characterized by the use of potential coronavirus antigenic polypeptides for the prevention, diagnosis or treatment of COVID-19 disease and other associated infectious diseases. Therefore, we present a series of inventions related to our invention.
[008] BR 10 2020 023728 4 A2 - ATIVIDADE ANTIVIRAL DE PEPTÍDEOS SINTÉTICOS CONTRA O NOVO CORONAVÍRUS SARS- COV-2. Essa invenção, peptídeos sintéticos produzidos com base na sequência de aminoácidos de proteínas vegetais, para o combate da infecção causada pelo SARS-CoV-2. Portanto, esta invenção não faz nenhuma menção a prevenção ou tratamento específico com nenhum peptídeos referente a SARS-CoV-2.[008] BR 10 2020 023728 4 A2 - ANTIVIRAL ACTIVITY OF SYNTHETIC PEPTIDES AGAINST THE NEW CORONAVIRUS SARS-COV-2. This invention, synthetic peptides produced based on the amino acid sequence of plant proteins, to combat the infection caused by SARS-CoV-2. Therefore, this invention makes no mention of prevention or specific treatment with any peptides relating to SARS-CoV-2.
[009] PI 0606148-6 A2 - ANTICORPOS MONOCLONAIS NEUTRALIZANTES CONTRA A SÍNDROME RESPIRATÓRIA AGUDA GRAVE ASSOCIADA COM O CORONAVÍRUS. Essa invenção fornece um anticorpo isolado capaz de ligar-se ao domínio de ligação do receptor da proteína spike da síndrome respiratória aguda grave - associada com o coronavírus (SARS-CoV) de forma a inibir competitivamente a ligação da SARS-CoV para as células principais. Contudo, esta invenção não faz nenhuma menção do uso de peptídeos referentes a esta proposta.[009] PI 0606148-6 A2 - NEUTRALIZING MONOCLONAL ANTIBODIES AGAINST SEVERE ACUTE RESPIRATORY SYNDROME ASSOCIATED WITH THE CORONAVIRUS. This invention provides an isolated antibody capable of binding to the receptor-binding domain of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike protein in order to competitively inhibit the binding of SARS-CoV to primary cells. . However, this invention makes no mention of the use of peptides relating to this proposal.
[010] BR 10 2021 000764 8 A2 - COMPOSIÇÃO E MÉTODO PARA OBTENÇÃO DE MEDICAMENTO COM ATIVIDADE ANTIVIRAL E ANTIBACTERIANA PARA SARS- COV-2 Essa invenção descreve a composição e metodologia para obtenção de um medicamento com atividade antiviral e antibacteriana. Contudo, esta invenção não faz nenhuma menção a utilização de polipeptídeos de SARS-CoV-2.[010] BR 10 2021 000764 8 A2 - COMPOSITION AND METHOD FOR OBTAINING A MEDICINE WITH ANTIVIRAL AND ANTIBACTERIAL ACTIVITY FOR SARS-COV-2 This invention describes the composition and methodology for obtaining a medicine with antiviral and antibacterial activity. However, this invention makes no mention of the use of SARS-CoV-2 polypeptides.
[011] CA3109607 (A1) - METHODS AND REAGENTS FOR DIAGNOSIS OF SARS- COV-2 INFECTION. A invenção descreve um método de para diagnosticar infecção por SARS-CoV-2 compreendendo a etapa de detecção da presença ou ausência de um anticorpo, preferencialmente anticorpo da classe IgA. Contudo, esta invenção não faz nenhuma menção do uso de polipeptídeos referentes a esta proposta.[011] CA3109607 (A1) - METHODS AND REAGENTS FOR DIAGNOSIS OF SARS-COV-2 INFECTION. The invention describes a method for diagnosing SARS-CoV-2 infection comprising the step of detecting the presence or absence of an antibody, preferably an IgA class antibody. However, this invention makes no mention of the use of polypeptides relating to this proposal.
[012] CA3115553 (A1) - ANTI-SARS-COV-2-SPIKE GLYCOPROTEIN ANTIBODIES AND ANTIGEN-BINDING FRAGMENTS. A invenção descreve anticorpos e seus fragmentos de ligação a antígeno que se ligam especificamente a uma proteína da espícula de coronavírus e métodos para usar tais anticorpos e fragmentos para tratar ou prevenir infecções virais (por exemplo, infecções por coronavírus). Contudo, esta invenção trabalha somente com a proteína da espícula viral e em nosso trabalho, não fazemos nenhuma menção do uso de polipeptídeos referentes a esta proteína.[012] CA3115553 (A1) - ANTI-SARS-COV-2-SPIKE GLYCOPROTEIN ANTIBODIES AND ANTIGEN-BINDING FRAGMENTS. The invention describes antibodies and antigen-binding fragments thereof that specifically bind to a coronavirus spike protein and methods for using such antibodies and fragments to treat or prevent viral infections (e.g., coronavirus infections). However, this invention only works with the viral spike protein and in our work, we make no mention of the use of polypeptides referring to this protein.
[013] EP3818989 A1 - PEPTIDES AND OLIGONUCLEOTIDES FOR A SARS-COV-2 VACCINE. A invenção refere-se a peptídeos derivados da glicoproteína da espícula viral de SARS-CoV-2 e os ácidos nucleicos que codificam para o mesmo. Contudo, esta invenção não faz nenhuma menção aos peptídeos aqui proposto.[013] EP3818989 A1 - PEPTIDES AND OLIGONUCLEOTIDES FOR A SARS-COV-2 VACCINE. The invention relates to peptides derived from the SARS-CoV-2 viral spike glycoprotein and the nucleic acids that encode it. However, this invention makes no mention of the peptides proposed here.
[014] A invenção refere-se a polipeptídeos sintéticos e derivados de regiões aminoacídicas do coronavírus SARS-CoV-2 que causa a Síndrome Respiratória Aguda Grave doença COVID-19. O polipeptídeo SEQ ID NO: 1 pode ser vantajosamente usado para diagnóstico ou vacinação ou tratamento contra coronavírus, e podem proteger contra outros agentes infecciosos, por exemplo, coronavírus SARS-CoV e MERS-CoV, além de outros vírus respiratóricos com outros coronavírus que possuem sintomas similares a gripe, visando sua aplicação tanto na medicina humana quanto veterinária.[014] The invention refers to synthetic polypeptides derived from amino acid regions of the SARS-CoV-2 coronavirus that causes Severe Acute Respiratory Syndrome, COVID-19. The polypeptide SEQ ID NO: 1 can be advantageously used for diagnosis or vaccination or treatment against coronaviruses, and can protect against other infectious agents, for example, coronaviruses SARS-CoV and MERS-CoV, in addition to other respiratory viruses with other coronaviruses that have flu-like symptoms, aiming for its application in both human and veterinary medicine.
[015] As abordagens atuais tanto no diagnóstico, imunobiológicos e tratamentos são baseadas principalmente em antígenos virais inteiros e não contemplam o risco procedente de reações cruzadas devido ao compartilhamento de determinantes imunológicos entre o vírus e o hospedeiro. Abordagens que utilizem polipeptídeos proteicos de SARS- CoV-2 que são bem conservadas e expostas à superfície (tornando esse potencial imunobiológico proposto, eficaz contra diferentes sorotipos e contra possíveis mutações dos vírus), além de serem preditos para ter eficiência de ligação de epítopo tanto para MHCs de classe I e II principalmente aos MHCs que possuem maior frequencia na população brasileira, e que não lidem com o potencial de reatividade cruzada, são extremamente vantajosos na produção de potenciais de tecnologia e inovação.[015] Current approaches to diagnosis, immunobiology and treatments are mainly based on whole viral antigens and do not consider the risk of cross-reactions due to the sharing of immunological determinants between the virus and the host. Approaches that utilize SARS-CoV-2 protein polypeptides that are well conserved and exposed to the surface (making this proposed immunobiological potential effective against different serotypes and against possible mutations of the viruses), in addition to being predicted to have epitope binding efficiency both for class I and II MHCs, especially MHCs that are more frequent in the Brazilian population, and that do not deal with the potential for cross-reactivity, are extremely advantageous in the production of technology and innovation potential.
[016] Para poder gerar imunidade de duração longa, o ideal é o polipeptídeo compreender pelo menos um epítopo de célula T e um epítopos de células B, que podem induzir anticorpos neutralizantes.[016] To be able to generate long-lasting immunity, the ideal is for the polypeptide to comprise at least one T cell epitope and one B cell epitope, which can induce neutralizing antibodies.
[017] Os inventores puderam demonstrar em análises in silico (Figura1) a existência de epítopos com o potencial imunológico (https://www.iedb.org/) nos motivos “motifs” (https://www.genome.jp/tools/motif/) (Figuras 2 e 3).[017] The inventors were able to demonstrate in in silico analyzes (Figure 1) the existence of epitopes with immunological potential (https://www.iedb.org/) in the “motifs” motifs (https://www.genome.jp/ tools/motif/) (Figures 2 and 3).
[018] Além disso, todos os polipeptídeos da presente invenção têm várias vantagens sobre quaisquer outras alternativas no possíveis diagnósticos, vacinas ou tratamento como curtos tempos de preparação, baixos custos de produção, são fáceis de armazenar e administrar, possuem perfil de segurança favorável e podem ser administrados de forma única ou repetida, por serem derivados proteicos de SARS- CoV-2, os peptídeos da invenção podem ser facilmente sintetizados.[018] Furthermore, all polypeptides of the present invention have several advantages over any other alternatives in possible diagnostics, vaccines or treatment such as short preparation times, low production costs, are easy to store and administer, have a favorable safety profile and can be administered singly or repeatedly, as they are protein derivatives of SARS-CoV-2, the peptides of the invention can be easily synthesized.
[019] Caracterizando-se efetivamente como uma alternativa na prevenção como potencial vacinal, diagnóstico ou tratamento de doenças infecciosas causadas por coronavírus ou doenças similares.[019] Effectively characterizing itself as an alternative in prevention as a potential vaccine, diagnosis or treatment of infectious diseases caused by coronaviruses or similar diseases.
[020] Nossas análises mostram que para os objetivos da presente invenção os polipeptídeos SEQ ID NO: 1, podem ter efeito de 0,1μg/kg a 4mg/kg.[020] Our analyzes show that for the purposes of the present invention, the polypeptides SEQ ID NO: 1 can have an effect from 0.1μg/kg to 4mg/kg.
[021] Do ponto de vista da administração destes polipeptídeos para a obtenção de efeitos preventivos, de diagnóstico ou terapêuticos para doenças causada por coronavírus ou doenças similares, utilizamos as seguintes alternativas.[021] From the point of view of administering these polypeptides to obtain preventive, diagnostic or therapeutic effects for diseases caused by coronaviruses or similar diseases, we use the following alternatives.
[022] A sequência polipeptídica relacionada com a presente invenção pode ser sintetizada artificialmente por qualquer equipamento de síntese polipeptídica existente in vitro e diferentes princípios técnicos. O método de obtenção inclui principalmente as etapas de síntese de polipeptídeos, purificação e coleta do produto final. Essas tecnologias serão desenvolvidas e programadas e são amplamente utilizadas em campos relacionados.[022] The polypeptide sequence related to the present invention can be artificially synthesized by any existing in vitro polypeptide synthesis equipment and different technical principles. The obtaining method mainly includes the steps of polypeptide synthesis, purification and collection of the final product. These technologies will be developed and programmed and are widely used in related fields.
[023] Os polipeptídeos da invenção pode ser conjugado com proteína de fusão com função de transporte e imunomoduladora de resposta imune derivada de um agente infeccioso, compreendendo uma proteína imunogênica (e.g., hemaglutinina de influenza, toxóide de difteria, toxóide de pertussis, toxóide de tétano e antígêno de superfície do vírus da hepatite B).[023] The polypeptides of the invention can be conjugated with a fusion protein with a transport and immune response immunomodulatory function derived from an infectious agent, comprising an immunogenic protein (e.g., influenza hemagglutinin, diphtheria toxoid, pertussis toxoid, tetanus and hepatitis B virus surface antigen).
[024] Os polipeptídeos da invenção pode ser administrado em combinação com outros potenciais imunogênicos de peptídeos derivados de patógenos virais e não virais (e. g., outros coronavírus), de preferência, peptídeos que estão presentes apenas nos patógenos e ausentes no hospedeiro humano.[024] The polypeptides of the invention can be administered in combination with other potential immunogenic peptides derived from viral and non-viral pathogens (e.g., other coronaviruses), preferably, peptides that are present only in the pathogens and absent in the human host.
[025] Polipeptídeos podem atuar sinergicamente com adjuvantes. Isso se aplica aos peptídeos da presente invenção na composição de pelo menos um adjuvante. O adjuvante pode ser, por exemplo, hidróxido de alumínio, fosfato de alumínio, alúmen (sulfato de alumínio), emulsão com MF59, lipídeo monofosforil A (MPL), adjuvante sistema 04 (AS04, monofosforil lipídeo A adsorvido em hidróxido de alumínio), oligonucleotídeos CpG, polylCLC, QS21 (extrato de saponina purificado), ISCOMs, por exemplo, adjuvante ISCOMATRIX, adjuvante completo de Freund (a/o emulsão de um óleo mineral, parafina e micobactérias inativadas), adjuvante de Freund incompleto (emulsão a/o de óleo mineral, parafina sem micobactéria), montanide ISA720, montanide ISA51 (ambas as emulsões a/o com esqualeno como óleo e mono-oleato como surfactante), sistema adjuvante 02 (AS02, compreendendo esqualeno e dois adjuvantes imunes hidrofóbicos, MPL e QS-21), lipossomas . De preferência, o adjuvante é admitido para uso em animais e em humanos.[025] Polypeptides can act synergistically with adjuvants. This applies to the peptides of the present invention in the composition of at least one adjuvant. The adjuvant may be, for example, aluminum hydroxide, aluminum phosphate, alum (aluminum sulfate), emulsion with MF59, monophosphoryl lipid A (MPL), adjuvant system 04 (AS04, monophosphoryl lipid A adsorbed on aluminum hydroxide), CpG oligonucleotides, polylCLC, QS21 (purified saponin extract), ISCOMs, e.g. ISCOMATRIX adjuvant, complete Freund's adjuvant (w/o emulsion of a mineral oil, paraffin and inactivated mycobacteria), incomplete Freund's adjuvant (w/o emulsion of mineral oil, paraffin without mycobacteria), montanide ISA720, montanide ISA51 (both w/o emulsions with squalene as oil and mono-oleate as surfactant), adjuvant system 02 (AS02, comprising squalene and two hydrophobic immune adjuvants, MPL and QS -21), liposomes. Preferably, the adjuvant is permitted for use in animals and humans.
[026] A composição pode, por exemplo, ser uma solução aquosa (à base de água). A solução também pode compreender um tampão fisiológico (PBS ou solução de Ringer). A composição pode ser adequada para administração em animais e humanos. A solução pode conter um conservante ou pode ser desprovida de conservantes.[026] The composition may, for example, be an aqueous (water-based) solution. The solution may also comprise a physiological buffer (PBS or Ringer's solution). The composition may be suitable for administration to animals and humans. The solution may contain a preservative or may be devoid of preservatives.
[027] Em alternativa, a solução pode ser seca (liofilizada) ou seca na forma de pulverização. Antes do uso, pode ser reconstituído em água para preparações injetáveis. Uma forma seca da composição da invenção pode compreender açucares como, por exemplo, trealose.[027] Alternatively, the solution can be dried (lyophilized) or dried in spray form. Before use, it can be reconstituted in water for injections. A dry form of the composition of the invention may comprise sugars such as, for example, trehalose.
[028] ASTUTI, I. Y. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response. Diabetes Metab Syndr.v. 14, n. 4, p.407-412. 2020.[028] ASTUTI, I. Y. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response. Diabetes Metab Syndr.v. 14, no. 4, p.407-412. 2020.
[029] BRASIL. Ministério da Saúde (BR). Painel de casos de doença pelo coronavírus 2019 (COVID-19) no Brasil pelo Ministério da Saúde [Internet]. Brasília: Ministério da Saúde; 2020. [Acesso em: 12 Jul. 2021]. Disponível em: https://covid.saude.gov.br/[029] BRAZIL. Ministry of Health (BR). Panel of coronavirus disease 2019 (COVID-19) cases in Brazil by the Ministry of Health [Internet]. Brasília: Ministry of Health; 2020. [Accessed on: 12 Jul. 2021]. Available at: https://covid.saude.gov.br/
[030] DONG, et al. An interactive web-based dashboard to track COVID-19 in real time. The Lancet infectious diseases, v. 20, n. 5, p. 533534, 2020.[030] DONG, et al. An interactive web-based dashboard to track COVID-19 in real time. The Lancet infectious diseases, vol. 20, no. 5, p. 533534, 2020.
[031] LEE, C. Yi-Pin et al. Serological approaches for COVID-19: epidemiologic perspective on surveillance and control. Frontiers in immunology, v. 11, p. 879, 2020.[031] LEE, C. Yi-Pin et al. Serological approaches for COVID-19: epidemiological perspective on surveillance and control. Frontiers in immunology, vol. 11, p. 879, 2020.
[032] LOBO, A. P. et al. COVID-19 epidemic in Brazil: Where are we at?. International Journal of Infectious Diseases, v. 97, p. 382-385, 2020.[032] LOBO, A. P. et al. COVID-19 epidemic in Brazil: Where are we at?. International Journal of Infectious Diseases, vol. 97, p. 382-385, 2020.
[033] MARINHO, P. R. D. et al. Covid-19 in Brazil: A sad scenario. Cytokine & Growth Factor Reviews, 2020.[033] MARINHO, P. R. D. et al. Covid-19 in Brazil: A sad scenario. Cytokine & Growth Factor Reviews, 2020.
Claims (10)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| BR102022005518-1A BR102022005518A2 (en) | 2022-03-23 | 2022-03-23 | SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS ANTIGEN POLYPEPTIDE PROCESS AND ITS APPLICATION |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| BR102022005518-1A BR102022005518A2 (en) | 2022-03-23 | 2022-03-23 | SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS ANTIGEN POLYPEPTIDE PROCESS AND ITS APPLICATION |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BR102022005518A2 true BR102022005518A2 (en) | 2023-10-03 |
Family
ID=89024662
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR102022005518-1A BR102022005518A2 (en) | 2022-03-23 | 2022-03-23 | SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS ANTIGEN POLYPEPTIDE PROCESS AND ITS APPLICATION |
Country Status (1)
| Country | Link |
|---|---|
| BR (1) | BR102022005518A2 (en) |
-
2022
- 2022-03-23 BR BR102022005518-1A patent/BR102022005518A2/en unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Sui et al. | Cross-protection against influenza virus infection by intranasal administration of M1-based vaccine with chitosan as an adjuvant | |
| Sui et al. | Cross-protection against influenza virus infection by intranasal administration of M2-based vaccine with chitosan as an adjuvant | |
| US20210085778A1 (en) | Parenteral norovirus vaccine formulations | |
| KR960003378B1 (en) | Vaccine preparation | |
| CN111892648B (en) | Novel coronavirus polypeptide vaccine coupled with TLR7 agonist and application thereof | |
| ES2307494T3 (en) | VACCINE OF THE VIRUS OF THE INFECTIVE FLU FOR ITS ADMINISTRATION VIA ORAL NASALU. | |
| US11382969B2 (en) | Vaccines against Hepatitis B virus | |
| Tamura et al. | Enhancement of protective antibody responses by cholera toxin B subunit inoculated intranasally with influenza vaccine | |
| EA014353B1 (en) | Vaccine compositions comprising a saponin adjuvant | |
| EP3818989A1 (en) | Peptides and oligonucleotides for a sars-cov-2 vaccine | |
| JP2019195328A (en) | Methods and compositions for dengue virus vaccines | |
| US20230330205A1 (en) | Norovirus vaccine | |
| Zhou et al. | RBD conjugate vaccine with a built-in TLR1/2 agonist is highly immunogenic against SARS-CoV-2 and variants of concern | |
| Tamura et al. | Protection against influenza virus infection by a two-dose regimen of nasal vaccination using vaccines combined with cholera toxin B subunit | |
| US20220054621A1 (en) | Norovirus vaccine formulations and methods | |
| ES2924914T3 (en) | Human rhinovirus vaccine | |
| de Oya et al. | Maternal transfer of antibodies to the offspring after mice immunization with insect larvae-derived recombinant hepatitis E virus ORF-2 proteins | |
| JP2015525794A (en) | Method for eliciting an immune response against RSV and Bordetella pertussis in infants | |
| Glück | Intranasal immunization against influenza | |
| Horwood et al. | Pneumococcal and influenza vaccination: current situation and future prospects | |
| BR102022005518A2 (en) | SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS ANTIGEN POLYPEPTIDE PROCESS AND ITS APPLICATION | |
| BR112021007668A2 (en) | immunogenic compositions | |
| AU2006310555B2 (en) | Prime boost vaccine for the protection of equines against equine influenza | |
| CA2728374A1 (en) | Compositions comprising salmonella porins and uses thereof as adjuvants and vaccines | |
| JP2024520730A (en) | Virus-like particle vaccines against coronaviruses |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B03A | Publication of a patent application or of a certificate of addition of invention [chapter 3.1 patent gazette] |