Proteins mimicking epitope of HIV-1 virus neutralizing antibody induce virus-neutralizing sera in mice

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F19%3AN0000356" target="_blank" >RIV/00027162:_____/19:N0000356 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/86652036:_____/19:00511409 RIV/61989592:15110/19:73596349 RIV/00027162:_____/19:N0000216

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S2352396419304505" target="_blank" >https://www.sciencedirect.com/science/article/pii/S2352396419304505</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ebiom.2019.07.015" target="_blank" >10.1016/j.ebiom.2019.07.015</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Proteins mimicking epitope of HIV-1 virus neutralizing antibody induce virus-neutralizing sera in mice

Popis výsledku v původním jazyce

Background The development of an effective vaccine preventing HIV-1 infection is hindered by the enormous antigenic variability and unique biochemical and immunological properties of HIV-1 Env glycoprotein, the most promising target for HIV-1 neutralizing antibody. Functional studies of rare elite neutralizers led to the discovery of broadly neutralizing antibodies. Methods We employed a highly complex combinatorial protein library derived from a 5 kDa albumin-binding domain scaffold, fused with support protein of total 38 kDa, to screen for binders of broadly neutralizing antibody VRC01 paratope. The most specific binders were used for immunization of experimental mice to elicit Env-specific antibodies and to test their neutralization activity using a panel of HIV-1 clade C and B pseudoviruses. Findings Three most specific binders designated as VRA017, VRA019, and VRA177 exhibited high specificity to VRC01 antibody. Immunized mice produced Env-binding antibodies which neutralize eight of twelve HIV-1 Tier 2 pseudoviruses. Molecular modelling revealed a shape complementarity between VRA proteins and a part of VRC01 gp120 interacting surface. Interpretation This strategy based on the identification of protein replicas of broadly neutralizing antibody paratope represents a novel approach in HIV-1 vaccine development. This approach is not affected by low immunogenicity of neutralization-sensitive epitopes, variability, and unique biochemical properties of HIV-1 Env used as a crucial antigen in the majority of contemporary tested vaccines.

Název v anglickém jazyce

Proteins mimicking epitope of HIV-1 virus neutralizing antibody induce virus-neutralizing sera in mice

Popis výsledku anglicky

Background The development of an effective vaccine preventing HIV-1 infection is hindered by the enormous antigenic variability and unique biochemical and immunological properties of HIV-1 Env glycoprotein, the most promising target for HIV-1 neutralizing antibody. Functional studies of rare elite neutralizers led to the discovery of broadly neutralizing antibodies. Methods We employed a highly complex combinatorial protein library derived from a 5 kDa albumin-binding domain scaffold, fused with support protein of total 38 kDa, to screen for binders of broadly neutralizing antibody VRC01 paratope. The most specific binders were used for immunization of experimental mice to elicit Env-specific antibodies and to test their neutralization activity using a panel of HIV-1 clade C and B pseudoviruses. Findings Three most specific binders designated as VRA017, VRA019, and VRA177 exhibited high specificity to VRC01 antibody. Immunized mice produced Env-binding antibodies which neutralize eight of twelve HIV-1 Tier 2 pseudoviruses. Molecular modelling revealed a shape complementarity between VRA proteins and a part of VRC01 gp120 interacting surface. Interpretation This strategy based on the identification of protein replicas of broadly neutralizing antibody paratope represents a novel approach in HIV-1 vaccine development. This approach is not affected by low immunogenicity of neutralization-sensitive epitopes, variability, and unique biochemical properties of HIV-1 Env used as a crucial antigen in the majority of contemporary tested vaccines.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

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

2019

Kód důvěrnosti údajů

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

Název periodika

EBIOMEDICINE

ISSN

2352-3964

e-ISSN

—

Svazek periodika

47

Číslo periodika v rámci svazku

September 2019

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

10

Strana od-do

247-256

Kód UT WoS článku

000486976200036

EID výsledku v databázi Scopus

2-s2.0-85072567469