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HIV (human immunodeficiency virus) immunogen and preparation method thereof

An immunogen and antigen epitope technology, applied to medical preparations containing active ingredients, antibody medical ingredients, peptides, etc., can solve the problems of inability to neutralize antibodies and high HIV mutation frequency

Inactive Publication Date: 2012-07-11
JILIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In order to solve the problem in the prior art that antibodies cannot neutralize the mutated HIV due to the high frequency of HIV mutation, the present invention provides an HIV immunogen, including a peptide sequence, which includes HIV 4E10 And / or at least one of the 2F5 and / or Z13 epitope sequences, simulating the natural state before the fusion of the MPER region on gp41 of the HIV virus, so that it can produce more specific antibodies

Method used

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  • HIV (human immunodeficiency virus) immunogen and preparation method thereof
  • HIV (human immunodeficiency virus) immunogen and preparation method thereof
  • HIV (human immunodeficiency virus) immunogen and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0038] Antigen epitope design

[0039] The 4E10 and / or 2F5 recognition epitope on HIV-1 gp41 MPER is selected as the antigenic epitope. Synthesize the following amino acid sequence:

[0040]

[0041]

[0042] In addition, universal Th cell epitopes can also be added.

Embodiment 2

[0044] Synthetic Antigen Peptide and Antibody Binding Activity Characterization

[0045]The synthesized antigen polypeptide was subjected to Tricine electrophoresis, the 4E10 antibody was used as the primary antibody, and the AP-labeled anti-human secondary antibody was used. The results are shown in figure 1 .

[0046] Depend on figure 1 It can be seen that the 4E10 epitope linear peptide, 4E10 and 2F5 biepitope linear peptide all have binding activity to HIV broad-spectrum neutralizing antibody 4E10, which is superior to the control tetrabranched peptide including only unrelated peptide sequences.

[0047] It shows that the immunogen of the present invention can form the correct epitope structure and combine with the corresponding antibody.

Embodiment 3

[0049] Guinea Pig Immunization Experiment of HIV Vaccine

[0050] The experiment was divided into 4 groups, with 8 guinea pigs in each group. Group 2: MPER epitope linear peptide + Freund's adjuvant; Group 4: MPER epitope linear peptide + water-type adjuvant.

[0051] Guinea pigs were injected subcutaneously (extremities) at multiple points, and boosted once every 15 days after the initial immunization, 0.5ug / g body weight. After the four immunizations, blood was collected from the heart to detect the antibody production against MPER, and the neutralizing activity was evaluated according to the antibody titer. Binding antibody detection process: peptide-coated well → BSA blocking → serum to be tested → goat anti-guinea pig IgG-HRP → TMB → OD450. Serum dilution 1:30.

[0052] Experimental results

[0053] The production of antibodies against MPER is shown in Table 1.

[0054] Antibody neutralizing activity evaluation is shown in Table 2.

[0055] Table 1. 4E10 epitope MAP...

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Abstract

The present invention relates to an HIV (human immunodeficiency virus) immunogen that stimulates broad-spectrum neutralizing antibodies and a vaccine prepared from the HIV immunogen. The HIV immunogen contains a peptide sequence which comprises HIV 4E10 and / or 2F5 and / or Z13 epitope sequences. The immunogen of this invention can stimulate HIV-specific broad-spectrum neutralizing antibodies, and overcomes the delaying problem of antibody induction due to high variability of HIV in the prior art. Animal immune experiments show that the peptide immunogen of the invention supplemented with adjuvants can induce production of specific antibodies in sera of immunized animals, and the induced antibodies has the capacity of broadly neutralizing representative HIV infected cells, and has the potential for development of clinical vaccines against HIV and auxiliary enhancement of HIV vaccine.

Description

technical field [0001] The invention relates to an HIV immunogen that induces broad-spectrum neutralizing antibodies and a vaccine prepared therefrom, in particular to a novel HIV vaccine with broad-spectrum protective effect. Background technique [0002] AIDS is one of the most important challenges facing the world, seriously jeopardizing social progress and economic growth. It has caused more than 60 million people to be infected, of which 30 million people have died. Currently, there are about 33.2 million infected people, of which more than 90% of cases occur in developing countries. [0003] So far, with the strong support of governments and international organizations, more than 100 clinical trials have been carried out in the world, but there is not yet a successful AIDS vaccine on the market. One of the main reasons for the difficulty in the development of AIDS vaccines is due to the particularity of HIV, that is, HIV-1 has a high degree of variability. The antige...

Claims

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Application Information

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IPC IPC(8): C07K14/155C07K19/00A61K39/21A61K39/295A61P31/18
Inventor 单亚明孔维张丽双
Owner JILIN UNIV
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