Immunogenic potential of different variants of HIV-1gp140 SOSIP

Kód výsledku v IS VaVaI

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Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Immunogenic potential of different variants of HIV-1gp140 SOSIP

Popis výsledku v původním jazyce

HIV-1 represents one of the major global health issues. More than 30 years of research have not led to development of efficient vaccines. 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 influence the folding and the interaction between virus and host cell receptor and thus virus infectivity. Although N-glycans may serve as shield against neutralizing antibodies, several broadly neutralizing antibodies identified in HIV-1 infected subjects target N-glycans and block viral infection. However, it is difficult to produce such antibodies by immunization. Trials testing immunogenic potential of recombinant gp120 monomer failed to demonstrate efficacy and protection from infection or disease progression. Several other strategies have been developed to elicit sufficient amount of neutralizing antibodies. One of them is the effort to create trimeric form of recombinant gp120.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 examinedfor 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.

Název v anglickém jazyce

Immunogenic potential of different variants of HIV-1gp140 SOSIP

Popis výsledku anglicky

HIV-1 represents one of the major global health issues. More than 30 years of research have not led to development of efficient vaccines. 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 influence the folding and the interaction between virus and host cell receptor and thus virus infectivity. Although N-glycans may serve as shield against neutralizing antibodies, several broadly neutralizing antibodies identified in HIV-1 infected subjects target N-glycans and block viral infection. However, it is difficult to produce such antibodies by immunization. Trials testing immunogenic potential of recombinant gp120 monomer failed to demonstrate efficacy and protection from infection or disease progression. Several other strategies have been developed to elicit sufficient amount of neutralizing antibodies. One of them is the effort to create trimeric form of recombinant gp120.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 examinedfor 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.

Druh

D - Stať ve sborníku

CEP obor

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OECD FORD obor

30102 - Immunology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

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

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název statě ve sborníku

11th International Conference Drug Delivery Systems Nanotechnology for Healthcare: Progress in Recombinant Vaccines, Molecular Adjuvants, Modern Drug Delivery Systems and Cell Therapy

ISBN

978-80-907074-6-7

ISSN

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e-ISSN

neuvedeno

Počet stran výsledku

9

Strana od-do

32-40

Název nakladatele

Nakladatelství Machovský

Místo vydání

Olomouc

Místo konání akce

Telč

Datum konání akce

5. 6. 2018

Typ akce podle státní příslušnosti

WRD - Celosvětová akce

Kód UT WoS článku

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