Immunogenic potential of different variants of HIV-1 gp140 SOSIP

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F18%3AN0000216" target="_blank" >RIV/00027162:_____/18:N0000216 - isvavai.cz</a>

Result on the web

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DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Immunogenic potential of different variants of HIV-1 gp140 SOSIP

Original language description

HIV-1 vaccines have currently limited efficacy caused by high variability and difficulties to produce appropriately folded recombinant envelope trimeric glycoprotein, gp120/gp41, which is one of the target for neutralizing antibodies. 50 % of the total mass of gp120 subunit is comprised by N-glycans which may serve as shield against and also target for several broadly neutralizing antibodies identified in HIV-1 infected subjects. Trials testing immunogenic potential of recombinant gp120 monomer failed to demonstrate efficacy. Several other strategies have been developed. Proteoliposomes represent corpuscular vaccine formulation with excellent biocompatibility. We immunized guinea pigs successively with recombinant clade C HIV-1 gp140 SOSIP trimer derived from acute stage of infection (transmitted founder (gp140 SOSIP TF)) and chronic stage - one year (gp140 SOSIP Y1) and three years (gp140 SOSIP Y3) after seroconversion or with only one variant. Sera were examined for antibodies targeting glycosylated and deglycosylated gp140 SOSIP proteins. Successive immunizations with gp140 SOSIP variants led to production of high titers of antibodies targeting gp140 SOSIP. There was no significant difference in antibodies amount targeting gp140 SOSIP TF and Y1 between groups. However, group immunized only with Y3 variant eluted significantly higher titers of antibodies targeting Y3 variant than groups immunized with TF or Y1 variants. Deglycosylation of gp140 SOSIP TF used for hyperimmune sera evaluation with N-glycanase F, removing N-linked glycans, led to increase in reactivity of sera in comparison to glycosylated variant. Nevertheless, deglycosylation of gp140 SOSIP Y1 and Y3 didn´t affect reactivity of sera. Interestingly, deglycosylation of all gp140 SOSIP with Endo H, cleaving mannose-rich oligosacharides, significantly increased reactivity of all sera. Successive immunization with Env from various stages of the HIV-1 infection could lead to preferential recognition of either protein or glycan moiety of Env.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

30102 - Immunology

Project

<a href="/en/project/NV15-32198A" target="_blank" >NV15-32198A: Construction of recombinant mimotopes for induction of neutralizing antibodies against HIV-1 gp120 glycoprotein using high-affinity binders approach</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů