Proteins mimicking epitope of HIV-1 virus neutralizing antibody induce virus-neutralizing sera in mice
The result's identifiers
Result code in 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>
Alternative codes found
RIV/86652036:_____/19:00511409 RIV/61989592:15110/19:73596349 RIV/00027162:_____/19:N0000216
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Proteins mimicking epitope of HIV-1 virus neutralizing antibody induce virus-neutralizing sera in mice
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30102 - Immunology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
EBIOMEDICINE
ISSN
2352-3964
e-ISSN
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Volume of the periodical
47
Issue of the periodical within the volume
September 2019
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
10
Pages from-to
247-256
UT code for WoS article
000486976200036
EID of the result in the Scopus database
2-s2.0-85072567469