CN101116745B - Human papilloma virus sample particle vaccines - Google Patents
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- CN101116745B CN101116745B CN2006100170737A CN200610017073A CN101116745B CN 101116745 B CN101116745 B CN 101116745B CN 2006100170737 A CN2006100170737 A CN 2006100170737A CN 200610017073 A CN200610017073 A CN 200610017073A CN 101116745 B CN101116745 B CN 101116745B
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Abstract
The invention relates to a virus-like particle vaccine against human papilloma virus, belonging to the biotechnology field. One milliliter vaccine contains the following components: HPV6L1VLPs: 10-60 ug, HPV16L1VLPs: 5-40 ug and HPV58L1VLPs10-60 ug. The invention has the advantages that HPV6L1, HPV16L1 and HPV58L1 proteins are secreted and expressed respectively, and the L1 proteins can be self-assembled to be VLPs. According to the infection epidemiology investigation result of human papilloma virus in some placed in Asia and China, the vaccine prepared by VLPs which is obtained by L1 proteins of HPV6, HPV16 and HPV58 can prevent 60 percent of the inventions resulting from HPV. The additional HPV type can further increases preventive effects of the vaccine.
Description
Technical field
The present invention relates to utilize purification others' human papillomavirus of different shaped (HumanPapillomavirns, HPV) virus-like particle (VLPs) that is self-assembled into of late protein L1 is through the proper proportion compatibility, preparation HPV vaccine is used to the part disease of preventing HPV to cause.
Background technology
HPV is a class double-chain small molecule DNA viruses, has strict species specificity, and the skin and the mucosal tissue of main infected person cause the proliferative lesion of corresponding site epithelial tissue.Can be divided into two groups of skin-type and mucosal patterns according to infection site, mucosal pattern HPV is again according to causing that the character of pathological changes is divided into two classes: cause mucous epithelium hyperplasia of prostate pathological changes low risk and with the closely-related high-risk-type of the multiple organ malignant tumour of the mankind (as cervical cancer, carcinoma of penis, larynx and head and neck cancer, bronchogenic carcinoma, the esophageal carcinoma, oral cancer etc.).According to nucleic acid sequence homology, it is 100 many types of that HPV can be divided into, and other HPV of different shaped causes different diseases.HPV1,2,3,4,7,10,26-29 cause optimum wart in normal or immunodeficiency is individual.HPV5,8,9,12,14,15,17,19-25,36,46-50 cause the flat damage in the immunodeficiency individuality.HPV6,11,34,39,41-44,51-55 cause that non-pernicious condyloma latum takes place for reproductive tract or respiratory mucosa.
The complete about 55nm of HPV virion diameter is made up of virus genom DNA and capsid two parts, no peplos, and capsid is icosahedron, is made up of 72 capsomeres, and the buoyant density of virion in CsCl is 1.34g/cm
3Viral genome is a double-stranded cyclic DNA, about 8kb.Genome contains at least 8 open reading frame (ORF), can be partly or entirely overlapping between each ORF, genome is divided into three functional areas according to function: early stage district, 6 non-structural proteins (E1, E2, E4, E5, E6, E7) of encoding, encoded protein with virus duplicate, transcribe with transformation relevant: late region, contain two ORF of L1, L2, encode main capsid protein L 1 and two structural protein of less important capsid protein L2 participate in the assembling of virion; LCR (LCR) claims noncoding region or upstream regulatory region again, any albumen of not encoding, but contain multiple controlling elements such as origin of replication, promoter, enhancer, silencer, what influence was viral duplicates and transcribes.The HPV capsid is to be made of jointly L1 and L2 albumen, about 5: 1 of the two ratio.Independent L1 albumen can spontaneously be assembled into the VLPs of diameter and the ripe virus size of HPV close (about 55nm), and the plesiomorphism of VLPs and natural HPV virus all is an icosahedral structure of virus, just the inner virus-free nucleic acid of VLP.
Vaccine control HPV relevant disease is a research focus in recent years.Owing to can't obtain a large amount of HPV virus by tissue culture at present, and consider the potential carcinogenecity of HPVE6, E7 gene, therefore, can not obtain the HPV vaccine by traditional vaccine preparation methods such as attenuated live vaccine or inactivated vaccines.Follow the development of molecular biology and technique for gene engineering, the HPV vaccine research mainly concentrates on VLPs vaccine, recombinant viral vaccine, subunit vaccine etc. at present.The VLPs vaccine mainly is to be first-selected destination protein with HPV master's capsid protein L 1, HPVL1 albumen is expressed in prokaryotic expression system, yeast expression system and baculovirus expression system respectively, and can be self-assembled into VLPs, its zoopery and part clinical experiment result show that the VLPs that L1 albumen is assembled into has good immunogenicity.
Research about the HPV vaccine component the earliest mainly concentrates on HPV6, HPV11, HPV16 and HPV18, Britain Ge Lansu company expresses HPV16 and HPV18 respectively at baculovirus expression system, Merck company has expressed the L1 albumen of HPV16,18, types such as 6 and 11 respectively in the saccharomyces cerevisiae expression system, gained albumen can form virus-like particle.The compatibility composition of these vaccines is based on the Epidemiological study result of American-European some areas, also mainly is the viral prevalence strain at the locality.Yet whole world epidemiology overall investigation result of study shows that HPV causes that the type of malignant tumor is not quite similar all over the world.Wherein HPV16 is topmost carcinogenic factor, other types are different with tumorigenic dependency all over the world, Epidemiological study result in China and Asia shows, the generation height correlation of HPV58 and cervical cancer, the infection rate of pertinent literature report HPV58 reaches more than 10%, considerably beyond HPV18 (4%), this with Europe, America and Africa the epidemiological survey result different.
Summary of the invention
The invention provides a kind of vaccine combination by different type HPV virus-like particle compatibilities that can prevention of human papillomavirus infection: comprising other VLPs of different shaped such as HPV 6L1VLPs, HPV16L1VLPs and HPV 58L1VLPs, wherein the content of each component is respectively in every milliliter of vaccine: HPV6L1VLPs:10～60 μ g, HPV16L1VLPs:5～40 μ g and HPV58L1:VLPs10～60 μ g.Wherein said vaccine component can add the VLPs of one or both other HPV types.Wherein additional HPV type comprises: HPV1, HPV 2, HPV 3, HPV 5, HPV 8, HPV 10, HPV 11, HPV 18, HPV 31, HPV 33, HPV 35, HPV 45, HPV 52, HPV 53, HPV 57 and HPV 59.
At first obtain reorganization VLPs, purity is mixed the various type VLPs of gained greater than 95%, and the VLPs mixture is mixed with adjuvant, prepares the vaccine of energy prevention of human papillomavirus infection.
The present invention has following advantage: 1) difference secreting, expressing HPV6L1, HPV16L1 and HPV58L1 albumen, the various L1 albumen of gained can be self-assembled into VLPs.2), use the infection that the vaccine of the VLPs preparation that the L1 albumen of types such as HPV6, HPV16 and HPV58 forms can prevent 60%HPV to cause according to the human papilloma virus infection Epidemiological study result who carries out in Asia and Chinese some areas.Additional HPV type can further improve the prevention of vaccine and render a service.
Description of drawings
Fig. 1 illustrates reorganization HPV6, HPV16 and HPV58VLPs mixture electromicroscopic photograph.
Fig. 2 illustrates reorganization HPV6, HPV11, HPV16, HPV18 and HPV58VLPs mixture electromicroscopic photograph.
Fig. 3 illustrates in the mouse immune, at unit price HPV6 vaccine with at the comparison of the antibody response of HPV6 in HPV6, HPV16 and the HPV58 vaccine.
Fig. 4 illustrates in the mouse immune, at unit price HPV6 vaccine with at the comparison of the antibody response of HPV6 in HPV6, HPV11, HPV16, HPV18 and the HPV58VLPs vaccine.
Fig. 5 illustrates in the mouse immune, at unit price HPV11 vaccine with at the comparison of the antibody response of HPV6 in HPV6, HPV11, HPV16, HPV18 and the HPV58VLPs vaccine.
Fig. 6 illustrates in the mouse immune, at unit price HPV16 vaccine with at the comparison of the antibody response of HPV6 in HPV6, HPV16 and the HPV58 vaccine.
Fig. 7 illustrates in the mouse immune, at unit price HPV16 vaccine with at the comparison of the antibody response of HPV6 in HPV6, HPV11, HPV16, HPV18 and the HPV58VLPs vaccine.
Fig. 8 illustrates in the mouse immune, at unit price HPV18 vaccine with at the comparison of the antibody response of HPV6 in HPV6, HPV11, HPV16, HPV18 and the HPV58VLPs vaccine.
Fig. 9 illustrates in the mouse immune, at unit price HPV58 vaccine with at the comparison of the antibody response of HPV6 in HPV6, HPV16 and the HPV58 vaccine.
Figure 10 illustrates in the mouse immune, at unit price HPV58 vaccine with at the comparison of the antibody response of HPV6 in HPV6, HPV11, HPV16, HPV18 and the HPV58VLPs vaccine.
The specific embodiment
Following examples are to be used to illustrate the present invention, but are not to limit its scope.
The preparation of embodiment 1HPV 6L1VLPs, HPV 16L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, the HPV16L1 of purification and three kinds of VLPs of HPV58L1 in 40 μ g: 20 μ g: the ratio of 40 μ g is mixed with mixed vaccine, adds the adjuvant aluminium hydroxide simultaneously, and final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 2HPV 6L1VLPs, HPV 11L1VLPs, HPV 16L1VLPs, HPV18L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV 11L1, HPV16L1, HPV 18L1 and five kinds of VLPs of HPV58L1 of purification in 40 μ g: 40 μ g: 20 μ g: 40 μ g: the ratio of 40 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
Embodiment 3 unit price VLPs and mixing VLPs vaccine immunogenicity are relatively
The unit price VLPs and the mixing VLPs vaccine that prepare are inoculated the Balb/C mice respectively, the mice random packet, 5 every group, the abdominal cavity inoculation was respectively at inoculation in 0,14,28 day.Got blood in back 28 days in inoculation and detect antibody titer with the ELISA method.
Embodiment 4ELISA method detects mice serum antibody
Be cushioned liquid with bag known antigens is diluted to 1 μ g/ml, every hole adds 0.1ml, and 4 ℃ are spent the night.Wash next day 3 times.Sample to be checked is through 2 times of serial dilutions, and high dilution is 1: 4096, get sample 0.1ml after the dilution be added to above-mentioned wrapped by reacting hole in, put 37 ℃ to hatch 1 hour washing.In reacting hole, add the enzyme mark second antibody 0.1ml of fresh dilution, hatched 30-60 minute for 37 ℃, washing, last is all over washing with DDW.The tmb substrate solution 0.1ml that in each reacting hole, adds interim preparation, 37 ℃ 10～30 minutes.In each reacting hole, add 2M sulphuric acid 0.05ml.The result judges: on the ELISA detector, survey the OD value in 450nm.Survey each hole OD value with zeroing back, blank hole, if it is greater than 2.1 times of the negative control OD value of stipulating, promptly positive.
The preparation of embodiment 5HPV 6L1VLPs, HPV 16L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, the HPV16L1 of purification and three kinds of VLPs of HPV58L1 in 10 μ g: 5 μ g: the ratio of 10 μ g is mixed with mixed vaccine, adds the adjuvant aluminium hydroxide simultaneously, and final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 6HPV 6L1VLPs, HPV 16L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, the HPV16L1 of purification and three kinds of VLPs of HPV58L1 in 60 μ g: 25 μ g: the ratio of 60 μ g is mixed with mixed vaccine, adds the adjuvant aluminium hydroxide simultaneously, and final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 7HPV 6L1VLPs, HPV 11L1VLPs, HPV 16L1VLPs, HPV18L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV 11L1, HPV16L1, HPV 18L1 and five kinds of VLPs of HPV58L1 of purification in 10 μ g: 10 μ g: 5 μ g: 10 μ g: the ratio of 10 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 8HPV 6L1VLPs, HPV 11L1VLPs, HPV 16L1VLPs, HPV18L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV 11L1, HPV16L1, HPV 18L1 and five kinds of VLPs of HPV58L1 of purification in 60 μ g: 60 μ g: 20 μ g: 60 μ g: the ratio of 60 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 9HPV 6L1VLPs, HPV 1L1VLPs, HPV 16L1VLPs, HPV31L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV 1L1, HPV16L1, HPV 31L1 and five kinds of VLPs of HPV58L1 of purification in 60 μ g: 60 μ g: 20 μ g: 60 μ g: the ratio of 60 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 10HPV 6L1VLPs, HPV 1L1VLPs, HPV 16L1VLPs, HPV31L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV 1L1, HPV16L1, HPV 31L1 and five kinds of VLPs of HPV58L1 of purification in 10 μ g: 10 μ g: 5 μ g: 10 μ g: the ratio of 10 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 11HPV 6L1VLPs, HPV 1L1VLPs, HPV 16L1VLPs, HPV31L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV 1L1, HPV16L1, HPV 31L1 and five kinds of VLPs of HPV58L1 of purification in 40 μ g: 40 μ g: 20 μ g: 40 μ g: the ratio of 40 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 12HPV 6L1VLPs, HPV 33L1VLPs, HPV 16L1VLPs, HPV45L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV 33L1, HPV16L1, HPV 45L1 and five kinds of VLPs of HPV58L1 of purification in 40 μ g: 40 μ g: 20 μ g: 40 μ g: the ratio of 40 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 13HPV 6L1VLPs, HPV 33L1VLPs, HPV 16L1VLPs, HPV45L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV33L1, HPV16L1, HPV 45L1 and five kinds of VLPs of HPV58L1 of purification in 10 μ g: 10 μ g: 5 μ g: 10 μ g: the ratio of 10 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 14HPV 6L1VLPs, HPV 33L1VLPs, HPV 16L1VLPs, HPV45L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV33L1, HPV16L1, HPV 45L1 and five kinds of VLPs of HPV58L1 of purification in 60 μ g: 60 μ g: 25 μ g: 60 μ g: the ratio of 60 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 15HPV 6L1VLPs, HPV 33L1VLPs, HPV 16L1VLPs, HPV45L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV33L1, HPV16L1, HPV 45L1 and five kinds of VLPs of HPV58L1 of purification in 60 μ g: 60 μ g: 25 μ g: 60 μ g: the ratio of 60 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 16HPV 6L1VLPs, HPV 2L1VLPs, HPV 16L1VLPs, HPV52L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV2L1, HPV16L1, HPV 52L1 and five kinds of VLPs of HPV58L1 of purification in 60 μ g: 60 μ g: 25 μ g: 60 μ g: the ratio of 60 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 17HPV 6L1VLPs, HPV 2L1VLPs, HPV 16L1VLPs, HPV52L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV2L1, HPV16L1, HPV 52L1 and five kinds of VLPs of HPV58L1 of purification in 10 μ g: 10 μ g: 5 μ g: 10 μ g: the ratio of 10 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 18HPV 6L1VLPs, HPV 2L1VLPs, HPV 16L1VLPs, HPV52L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV2L1, HPV16L1, HPV 52L1 and five kinds of VLPs of HPV58L1 of purification in 40 μ g: 40 μ g: 20 μ g: 40 μ g: the ratio of 40 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 19HPV 6L1VLPs, HPV 3L1VLPs, HPV 16L1VLPs, HPV53L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV3L1, HPV16L1, HPV 53L1 and five kinds of VLPs of HPV58L1 of purification in 40 μ g: 40 μ g: 20 μ g: 40 μ g: the ratio of 40 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 20HPV 6L1VLPs, HPV 3L1VLPs, HPV 16L1VLPs, HPV53L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV3L1, HPV16L1, HPV 53L1 and five kinds of VLPs of HPV58L1 of purification in 10 μ g: 10 μ g: 5 μ g: 10 μ g: the ratio of 10 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 21HPV 6L1VLPs, HPV 3L1VLPs, HPV 16L1VLPs, HPV53L1VLPs and HPV 58L1VLPs mixing VLPs vaccine with HPV6L1, HPV3L1, HPV16L1, HPV 53L1 and five kinds of VLPs of HPV58L1 of purification in 60 μ g: 60 μ g: 25 μ g: 60 μ g: the ratio of 60 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 22HPV 6L1VLPs, HPV 5L1VLPs, HPV 16L1VLPs, HPV35L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV5L1, HPV16L1, HPV 35L1 and five kinds of VLPs of HPV58L1 of purification in 60 μ g: 60 μ g: 25 μ g: 60 μ g: the ratio of 60 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 23HPV 6L1VLPs, HPV 5L1VLPs, HPV 16L1VLPs, HPV35L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV5L1, HPV16L1, HPV 35L1 and five kinds of VLPs of HPV58L1 of purification in 10 μ g: 10 μ g: 5 μ g: 10 μ g: the ratio of 10 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 24HPV 6L1VLPs, HPV 5L1VLPs, HPV 16L1VLPs, HPV35L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV5L1, HPV16L1, HPV 35L1 and five kinds of VLPs of HPV58L1 of purification in 40 μ g: 40 μ g: 20 μ g: 40 μ g: the ratio of 40 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 25HPV 6L1VLPs, HPV 8L1VLPs, HPV 16L1VLPs, HPV57L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV8L1, HPV16L1, HPV57L1 and five kinds of VLPs of HPV58L1 of purification in 40 μ g: 40 μ g: 20 μ g: 40 μ g: the ratio of 40 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 26HPV 6L1VLPs, HPV 8L1VLPs, HPV 16L1VLPs, HPV57L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV8L1, HPV16L1, HPV 57L1 and five kinds of VLPs of HPV58L1 of purification in 10 μ g: 10 μ g: 5 μ g: 10 μ g: the ratio of 10 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 27HPV 6L1VLPs, HPV 8L1VLPs, HPV 16L1VLPs, HPV57L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV8L1, HPV16L1, HPV 57L1 and five kinds of VLPs of HPV58L1 of purification in 60 μ g: 60 μ g: 25 μ g: 60 μ g: the ratio of 60 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 28HPV 6L1VLPs, HPV 10L1VLPs, HPV 16L1VLPs, HPV59L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV10L1, HPV16L1, HPV 597L1 and five kinds of VLPs of HPV58L1 of purification in 60 μ g: 60 μ g: 25 μ g: 60 μ g: the ratio of 60 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 29HPV 6L1VLPs, HPV 10L1VLPs, HPV 16L1VLPs, HPV59L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV10L1, HPV16L1, HPV 597L1 and five kinds of VLPs of HPV58L1 of purification in 40 μ g: 40 μ g: 20 μ g: 40 μ g: the ratio of 40 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
The preparation of embodiment 30HPV 6L1VLPs, HPV 10L1VLPs, HPV 16L1VLPs, HPV59L1VLPs and HPV 58L1VLPs mixing VLPs vaccine
With HPV6L1, HPV10L1, HPV16L1, HPV 597L1 and five kinds of VLPs of HPV58L1 of purification in 10 μ g: 10 μ g: 5 μ g: 10 μ g: the ratio of 10 μ g is mixed with mixed vaccine, add the adjuvant aluminium hydroxide simultaneously, final concentration is about 1mg/ml, after fully mixing, in 4 ℃ of preservations.
Claims (3)
1. a human papillomavirus virus sample particle vaccines, the content that it is characterized in that each component in every milliliter of vaccine is respectively: HPV6L1VLPs:10～60 μ g, HPV16L1VLPs:5～40 μ g and HPV58L1VLPs10～60 μ g, the VLPs of additional other HPV types of wherein said vaccine component, wherein additional HPV type comprises the VLPs:HPV1:10～60 μ g of one or both following types, HPV2:10～60 μ g, HPV3:10～60 μ g, HPV5:10～60 μ g, HPV8:10～60 μ g, HPV10:10～60 μ g, HPV11:10～60 μ g, HPV18:10～60 μ g, HPV31:10～60 μ g, HPV33:10～60 μ g, HPV35:10～60 μ g, HPV45:10～60 μ g, HPV52:10～60 μ g, HPV53:10～60 μ g, HPV57:10～60 μ g and HPV59:10～60 μ g.
2. human papillomavirus's as claimed in claim 1 virus sample particle vaccines wherein also comprises a kind of vaccine adjuvant.
3. human papillomavirus's as claimed in claim 2 virus sample particle vaccines, vaccine adjuvant is an aluminium hydroxide.
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| CN101914139B (en) * | 2010-07-16 | 2012-11-21 | 四川大学 | Human papilloma virus (HPV) capsid protein L1 polypeptide and preparation and application thereof |
| CN103992395B (en) * | 2013-02-18 | 2018-07-27 | 北京康乐卫士生物技术股份有限公司 | Recombinate the VLP vaccines and preparation method thereof of HPV-58 types L1 |
| CN110950935A (en) * | 2018-09-26 | 2020-04-03 | 厦门大学 | Mutant of human papilloma virus 51 type L1 protein |
| CN113088527B (en) * | 2021-04-23 | 2023-12-26 | 上海博唯生物科技有限公司 | Polynucleotide for expressing HPV53L1, expression vector, host cell and application thereof |
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| CN1498963A (en) * | 2002-11-08 | 2004-05-26 | 中国医学科学院基础医学研究所 | Method for producing virus like granules of human papilloma virus |
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