Characterization of antibody responses elicited by human immunodeficiency virus type 1 primary isolate trimeric and monomeric envelope glycoproteins in selected adjuvants.

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TitleCharacterization of antibody responses elicited by human immunodeficiency virus type 1 primary isolate trimeric and monomeric envelope glycoproteins in selected adjuvants.
Publication TypeJournal Article
Year of Publication2006
AuthorsLi, Y, Svehla, K, Mathy, NL, Voss, G, Mascola, JR, Wyatt, R
JournalJ Virol
Volume80
Issue3
Pagination1414-26
Date Published2006 Feb
ISSN0022-538X
KeywordsAdjuvants, Immunologic, Amino Acid Sequence, Animals, env Gene Products, Human Immunodeficiency Virus, Epitope Mapping, Gene Products, env, Guinea Pigs, HIV Antibodies, HIV Antigens, HIV Envelope Protein gp120, HIV-1, Humans, Molecular Sequence Data, Neutralization Tests, Peptide Fragments, Protein Structure, Quaternary
Abstract

We previously reported that soluble, stable YU2 gp140 trimeric human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein immunogens could elicit improved breadth of neutralization against HIV-1 isolates compared to monomeric YU2 gp120 proteins. In this guinea pig immunization study, we sought to extend these data and determine if adjuvant could quantitatively or qualitatively alter the neutralizing response elicited by trimeric or monomeric immunogens. Consistent with our earlier studies, the YU2 gp140 immunogens elicited higher-titer neutralizing antibodies against homologous and heterologous isolates than those elicited by monomeric YU2 gp120. Additionally, the GlaxoSmithKline family of adjuvants AS01B, AS02A, and AS03 induced higher levels of neutralizing antibodies compared to emulsification of the same immunogens in Ribi adjuvant. Further analysis of vaccine sera indicated that homologous virus neutralization was not mediated by antibodies to the V3 loop, although V3 loop-directed neutralization could be detected for some heterologous isolates. In most gp120-inoculated animals, the homologous YU2 neutralization activity was inhibited by a peptide derived from the YU2 V1 loop, whereas the neutralizing activity elicited by YU2 gp140 trimers was much less sensitive to V1 peptide inhibition. Consistent with a less V1-focused antibody response, sera from the gp140-immunized animals more efficiently neutralized heterologous HIV-1 isolates, as determined by two distinct neutralization formats. Thus, there appear to be qualitative differences in the neutralizing antibody response elicited by YU2 gp140 compared to YU2 monomeric gp120. Further mapping analysis of more conserved regions of gp120/gp41 may be required to determine the neutralizing specificity elicited by the trimeric immunogens.

DOI10.1128/JVI.80.3.1414-1426.2006
Alternate JournalJ. Virol.
PubMed ID16415019
PubMed Central IDPMC1346938