Epitopes for neutralizing antibodies induced by HIV-1 envelope glycoprotein BG505 SOSIP trimers in rabbits and macaques.

TitleEpitopes for neutralizing antibodies induced by HIV-1 envelope glycoprotein BG505 SOSIP trimers in rabbits and macaques.
Publication TypeJournal Article
Year of Publication2018
AuthorsKlasse PJ, Ketas TJ, Cottrell CA, Ozorowski G, Debnath G, Camara D, Francomano E, Pugach P, Ringe RP, Labranche CC, van Gils MJ, Bricault CA, Barouch DH, Crotty S, Silvestri G, Kasturi S, Pulendran B, Wilson IA, Montefiori DC, Sanders RW, Ward AB, Moore JP
JournalPLoS Pathog
Volume14
Issue2
Paginatione1006913
Date Published02/23/2018
ISSN1553-7374
KeywordsAIDS Vaccines, Animals, Antibodies, Neutralizing, Antibody Formation, env Gene Products, Human Immunodeficiency Virus, Epitopes, Female, HIV Antibodies, HIV Infections, HIV-1, Macaca mulatta, Protein Multimerization, Rabbits
Abstract

The native-like, soluble SOSIP.664 trimer based on the BG505 clade A env gene of HIV-1 is immunogenic in various animal species, of which the most studied are rabbits and rhesus macaques. The trimer induces autologous neutralizing antibodies (NAbs) consistently but at a wide range of titers and with incompletely determined specificities. A precise delineation of immunogenic neutralization epitopes on native-like trimers could help strategies to extend the NAb response to heterologous HIV-1 strains. One autologous NAb epitope on the BG505 Env trimer is known to involve residues lining a hole in the glycan shield that is blocked by adding a glycan at either residue 241 or 289. This glycan-hole epitope accounts for the NAb response of most trimer-immunized rabbits but not for that of a substantial subset. Here, we have used a large panel of mutant BG505 Env-pseudotyped viruses to define additional sites. A frequently immunogenic epitope in rabbits is blocked by adding a glycan at residue 465 near the junction of the gp120 V5 loop and β24 strand and is influenced by amino-acid changes in the structurally nearby C3 region. We name this new site the "C3/465 epitope". Of note is that the C3 region was under selection pressure in the infected infant from whom the BG505 virus was isolated. A third NAb epitope is located in the V1 region of gp120, although it is rarely immunogenic. In macaques, NAb responses induced by BG505 SOSIP trimers are more often directed at the C3/465 epitope than the 241/289-glycan hole.

DOI10.1371/journal.ppat.1006913
Alternate JournalPLoS Pathog.
PubMed ID29474444
PubMed Central IDPMC5841823
Grant ListP01 AI110657 / AI / NIAID NIH HHS / United States
P51 OD011132 / OD / NIH HHS / United States
R37 AI036082 / NH / NIH HHS / United States
1UM1 AI100663 / NH / NIH HHS / United States
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