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immune combination for inducing broad-spectrum neutralizing antibodies against HIV-1

A technology of HIV-1 and antibody, applied in the field of vaccines, to achieve the effect of prolonging the existence time

Pending Publication Date: 2020-08-07
SHANGHAI PUBLIC HEALTH CLINICAL CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These successful studies suggest that our sequential immunization strategy is very likely to induce the production of HIV-1 broad-spectrum neutralizing antibodies

Method used

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  • immune combination for inducing broad-spectrum neutralizing antibodies against HIV-1
  • immune combination for inducing broad-spectrum neutralizing antibodies against HIV-1
  • immune combination for inducing broad-spectrum neutralizing antibodies against HIV-1

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0110] Example 1: Evaluation of the Induction Effect of the Second Injection of Different Immunization Combinations on Broadly Neutralizing Antibodies in Mice

[0111] The mice were immunized with different immunization combinations, and the titers of neutralizing antibodies against HIV-1 pseudoviruses GX191.2, B16 and C2 induced by different immunization combinations were evaluated after 4 weeks of immunization.

[0112] The experimental steps are as follows: the mice were randomly divided into 7 groups, which were named DNA+DNA group, rTV+rTV group, rTV+DNA group, DNA+protein group, protein+DNA group, rTV group respectively according to different immunogen combination forms. +protein group and protein+rTV group. The specific immunization combinations are shown in Table 2.

[0113] The titers of neutralizing antibodies against HIV-1 pseudoviruses GX191.2, B16 and C2 produced by different immunization combinations are as follows: figure 1 Shown: When the combination of the s...

Embodiment 2

[0117] Example 2: Evaluation of the Inducing Effect of Different Immunization Combinations for the Third Injection on Widely Awareness Neutralizing Antibodies in Mice

[0118] According to the conclusion drawn in Example 1, the second dose is fixed as a poxvirus vector vaccine, and the third dose is optimized. C57 / BL6 mice were immunized with different immunization combinations. The immunogen was HIV-1 membrane protein, and the adjuvant was aluminum adjuvant. Titers of neutralizing antibodies to B16 and C2.

[0119] The experimental steps are as follows: the mice were randomly divided into 7 groups, which were named control group, protein-AE2F-SOSIP.664-ferritin group, rTV-AE2F-gp145 group, rTV-RL42-gp145 group according to the immunogen of the third injection group, Ad-RL42-gp145 group and DNA-AE2F-gp145 group. The specific immunization combinations are shown in Table 3. The titers of neutralizing antibodies against HIV-1 pseudoviruses GX191.2, B16 and C2 produced by diffe...

Embodiment 3

[0123] Example 3: Evaluation of the induction effect of broad-spectrum neutralizing antibodies in mice with different immunization combinations of the third and fourth doses

[0124] According to the conclusions drawn in Examples 1 and 2, the second dose was fixed as a poxvirus vector vaccine, and the recombinant protein vaccine and poxvirus vector vaccine that performed well in the third dose were selected, combined in three or four doses, and mice were immunized , 4 weeks after completion of immunization, evaluate the neutralizing antibody titers induced by different immunization combinations against HIV-1 pseudoviruses GX191.2, B16 and C2.

[0125] The experimental steps are as follows: the mice were randomly divided into 5 groups, which were named control group, protein+DNA group, protein+rTV group, rTV+protein group and protein+ Ad group. The specific immunization combinations are shown in Table 4.

[0126] The titers of neutralizing antibodies against HIV-1 pseudovirus...

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Abstract

The invention relates to the field of vaccines, in particular to a vaccine composition for inducing an HIV-1 broad-spectrum neutralizing antibody. A combined vaccine form is adopted, HIV-1 membrane protein is adopted as immunogen for the first time, and vaccine presentation forms include but are not limited to recombinant plasmid vaccines, recombinant protein subunit vaccines, recombinant virus vector vaccines, virus-like particle vaccines, nanoparticle vaccines, attenuated live vaccines and inactivated virus vaccines; the virus vector vaccine for expressing the HIV-1 membrane protein is adopted in the second injection, so that the titer and broad spectrum of an induced anti-HIV-1 neutralizing antibody can be remarkably improved; wherein the virus vector comprises but is not limited to poxvirus, adenovirus, herpes simplex virus, measles virus, enterovirus and rhabdovirus. And the third needle and the fourth needle are protein nanoparticle vaccine and virus vector vaccine combinations or vice versa. Inoculation modes of the vaccine include but are not limited to muscle inoculation, intracutaneous inoculation, subcutaneous inoculation, nasal dripping, aerosol inhalation, genital tract, rectum, oral administration and the like. Animal experiment results prove that the vaccine combination is safe, can continuously generate a high-titer broad-spectrum neutralizing antibody, and canbe used for preventing and treating AIDS in the future.

Description

technical field [0001] The invention relates to the field of vaccines, in particular to an immune combination for inducing broad-spectrum neutralizing antibodies against HIV-1. Background technique [0002] Human immunodeficiency virus type 1 (Human Immunodeficiency Virus Type 1, HIV-1) has the characteristics of high genome variation, glycosylation protection on the surface, and scarce membrane proteins on the surface of virus particles, which lead to the inability of the human body to produce effective immunity against HIV-1. Responses, which have brought very serious challenges to the development of HIV-1 vaccines. Among many HIV-1 vaccine clinical trials, Thailand's HIV-1 vaccine (RV-144) phase III clinical trial is currently the only proven effective vaccine, but its effective rate is only 31.2%. Therefore, it is necessary to deeply explore the characteristics of protective immune response and its generation mechanism in order to develop more effective vaccines. The r...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K39/21A61P31/18
CPCA61K39/395A61K39/12A61P31/18C12N2740/16034A61K2039/5256A61K2300/00
Inventor 徐建青张晓燕曹康丽丁相卿
Owner SHANGHAI PUBLIC HEALTH CLINICAL CENT
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