Provided are a nine-valent human papillomavirus vaccine and use thereof. The nine-valent human papillomavirus vaccine comprises HPV6, HPV11, HPV16, HPV18, HPV31, HPV33, HPV45, HPV52, and HPV58 type truncated L1-VLP antigens. All antigen components in the provided nine-valent HPV vaccine are derived from L1, a major capsid protein of the HPV, and truncated. The yield of the L1 protein is improved by means of a truncated L1 protein expressed by an Escherichia coli system, thereby reducing the production cost of the vaccine. Optimizing the particle size of each type of VLP antigens and the particle size of the aluminum hydroxide adjuvant, combined with control over the ratio of each type of VLP antigens to the adjuvant and the buffer system and the like, enables the obtained nine-valent HPV vaccine to induce a high-level immune response, especially to demonstrate a significant clinical effect.
A61K 39/295 - Antigènes viraux polyvalentsMélanges d'antigènes viraux et bactériens
A61K 39/39 - Préparations médicinales contenant des antigènes ou des anticorps caractérisées par les additifs immunostimulants, p. ex. par les adjuvants chimiques
A61P 31/20 - Antiviraux pour le traitement des virus ADN
Provided is a human papillomavirus vaccine. The vaccine is composed of L1 protein antigens of HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68. The recombinant fifteen-valent vaccine for human papillomavirus contains 12 types clearly related to human cancers, two most common low-risk types: HPV6 and HPV11, and a suspicious carcinogenic type: HPV68. In China, the prevention effect of the vaccine on female cervical cancer is expected to be improved to 97.2% or more, and globally, the prevention effect on female cervical cancer is expected to be improved to 94.1% or more, and the vaccine has a relatively high application value.
The present invention relates to a Tac promoter-based plasmid expression vector transformation and construction method, in which an SD sequence thereof is replaced and a tag sequence is further knocked out. The present invention also relates to a use of the constructed expression vector in recombinant exogenous protein expression, in particular a use of the expression vector in the expression of human papillomavirus L1 antigen protein, and a use of an L1 antigen protein expression product thereof in the prevention of cervical cancer.
A human papillomavirus (HPV) 56-type L1 protein mutant, a method for reducing the degradation of a recombinant HPV 56-type L1 protein, and an application. The modification of mutating the R at position 420 of an amino acid sequence of HPV56L1 into T or Q by using the genetic engineering technology successfully solves the problem of the degradation of the protein. The mutation does not affect the expression of a corresponding mutated L1 protein, the degradation ratio of a modified L1 protein is significantly reduced, and the immunogenicity of a corresponding VLP is not influenced. The HPV 56-type L1 protein is mutated and modified, so that the degradation problem is solved, the manufacturing difficulty is reduced, and the qualitative trait is improved. Thus, a corresponding HPV56L1-VLP obtained by recombinant expression of a modified sequence and assembly is more suitable as a vaccine antigen protein for preventing this type of papillomavirus infection.
A human papillomavirus type 51 L1 protein mutant, a method for reducing the degradation of a recombinant human papillomavirus type 51 L1 protein using same and the use thereof. The mutation of R at position 422 of the amino acid sequence of HPV51L1 into T or Q by means of a genetic engineering technique successfully solves a protein degradation problem thereof. Experiments show that the mutations both do not affect the expression of the corresponding mutated L1 protein, the degradation ratio of the modified L1 protein is obviously reduced, and the immunogenicity of the corresponding VLP is also not affected. By means of mutation of the human papillomavirus type 51 L1 protein, the protein degradation problem is avoided, so that the corresponding HPV51L1-VLP obtained by recombinant expression of the modified sequence or the assembly thereof is more suitable as a vaccine antigen protein to prevent this type of papillomavirus infection.
An expression of the human papilloma virus HPV39 L1 protein, virus-like particles, and a preparation method therefor. The preparation method comprises: truncating the amino acid sequence of the HPV39 L1 protein, carrying out codon optimization on a coding nucleotide sequence of the truncated protein to obtain an optimized coding nucleotide sequence, and lastly matching with a tag-free expression vector having a specific SD sequence to achieve tag-free expression and purification. By means of the described improvement, higher protein expression is obtained in prokaryotic expression systems such as an escherichia coli expression system, and VLPs having more consistent quality are obtained.
An expression of the human papilloma virus HPV35 L1 protein, virus-like particles, and a preparation method therefor. The preparation method comprises: truncating the amino acid sequence of the HPV35 L1 protein, carrying out codon optimization on a coding nucleotide sequence of the truncated protein to obtain an optimized coding nucleotide sequence, and lastly matching with a tag-free expression vector having a specific SD sequence to achieve tag-free expression and purification. By means of the described improvement, higher protein expression is obtained in prokaryotic expression systems such as an escherichia coli expression system, and VLPs having more consistent quality are obtained.
The expression of a human papillomavirus HPV59 L1 protein, and a virus-like particle and a preparation method therefor. The method comprises: truncating the amino acid sequence of the HPV59 L1 protein; performing codon optimization on the nucleotide sequence encoding the truncated protein to obtain an optimized encoding nucleotide sequence; and finally achieving untagged expression and purification with an untagged expression vector containing a specific SD sequence. By means of the above-mentioned improvement, a higher protein expression level can be obtained in a prokaryotic expression system such as an Escherichia coli expression system, and the VLP with more uniform quality can be obtained.
The present invention relates to the field of biomedicine, in particular to a recombinant subunit vaccine against respiratory syncytial virus (RSV) and a use thereof, and more in particular to a recombinant fusion protein containing the Head only (RHF) domain of an RSV envelope fusion protein F and a multimerization domain such as an immunoglobulin Fc fragment, an expression construct containing the recombinant fusion protein, a preparation method for the recombinant fusion protein, and an immunogenic composition containing the recombinant fusion protein, such as a vaccine.
The present invention relates to the field of medical biology, and specifically to expression of a human papillomavirus (HPV) 68 L1 protein, and virus-like particles (VLPs) and a preparation method therefor. The amino acid sequence of the HPV 68 L1 protein of a specific virus strain, especially AAZ39498.1, is truncated, codon optimization is carried out on the coding nucleotide sequence of the truncated protein to obtain an optimized coding nucleotide sequence, and finally tag-free expression and purification are achieved by using a tag-free expression vector containing a specific SD sequence. According to the present invention, by means of the improvement, a higher protein expression level can be obtained in a prokaryotic expression system such as an E. coli expression system, and VLPs having more uniform quality are obtained.
Disclosed in the present invention are an adjuvant for a novel coronavirus COVID-19 vaccine, and a developed bivalent vaccine thereof which contains antigens of a novel coronavirus epidemic HuB strain and a South African mutant strain B.1.351.
A61K 39/39 - Préparations médicinales contenant des antigènes ou des anticorps caractérisées par les additifs immunostimulants, p. ex. par les adjuvants chimiques
A61K 39/215 - Coronaviridae, p. ex. virus de la bronchite infectieuse aviaire
Disclosed is a fusion protein containing an antigen epitope of a novel coronavirus COVID-19 vaccine. The fusion protein consists of an antigen epitope fragment of the novel coronavirus COVID-19 vaccine and an immunoglobulin Fc fragment, wherein the antigen epitope fragment of the novel coronavirus COVID-19 vaccine is the RBD fragment and SD1 fragment in the S1 subunit. By means of research and exploration, it is found that SD1 is fused on the basis of an RBD, so that flexibility and variability can be increased, a head-to-tail structure is easily formed, the structure is more stable, and compared with the fusion of the RBD only, the present invention is more advantageous. Further, experiments show that the fusion protein of the antigen epitope obtained in the present invention has better immune characteristics and stability, and the effect is significantly better than the effect of fusing only the RBD.
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