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PMID: 16912322 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Antibody responses elicited in macaques immunized with human immunodeficiency virus type 1 (HIV-1) SF162-derived gp140 envelope immunogens: comparison with those elicited during homologous simian/human immunodeficiency virus SHIVSF162P4 and heterologous HIV-1 infection.

Journal of virology ·Vol. 80 ·No. 17 ·2006-09-00 ·Pages 8745-62

Derby NR, Kraft Z, Kan E, Crooks ET, Barnett SW, Srivastava IK, Binley JM, Stamatatos L

Abstract

The antibody responses elicited in rhesus macaques immunized with soluble human immunodeficiency virus (HIV) Env gp140 proteins derived from the R5-tropic HIV-1 SF162 virus were analyzed and compared to the broadly reactive neutralizing antibody responses elicited during chronic infection of a macaque with a simian/human immunodeficiency virus (SHIV) expressing the HIV-1 SF162 Env, SHIV(SF162P4), and humans infected with heterologous HIV-1 isolates. Four gp140 immunogens were evaluated: SF162gp140, DeltaV2gp140 (lacking the crown of the V2 loop), DeltaV3gp140 (lacking the crown of the V3 loop), and DeltaV2DeltaV3gp140 (lacking both the V2 and V3 loop crowns). SF162gp140 and DeltaV2gp140 have been previously evaluated by our group in a pilot study, but here, a more comprehensive analysis of their immunogenic properties was performed. All four gp140 immunogens elicited stronger anti-gp120 than anti-gp41 antibodies and potent homologous neutralizing antibodies (NAbs) that primarily targeted the first hypervariable region (V1 loop) of gp120, although SF162gp140 also elicited anti-V3 NAbs. Heterologous NAbs were elicited by SF162gp140 and DeltaV2gp140 but were weak in potency and narrow in specificity. No heterologous NAbs were elicited by DeltaV3gp140 or DeltaV2DeltaV3gp140. In contrast, the SHIV(SF162P4)-infected macaque and HIV-infected humans generated similar titers of anti-gp120 and anti-gp41 antibodies and NAbs of significant breadth against primary HIV-1 isolates, which did not target the V1 loop. The difference in V1 loop immunogenicity between soluble gp140 and virion-associated gp160 Env proteins derived from SF162 may be the basis for the observed difference in the breadth of neutralization in sera from the immunized and infected animals studied here.

MeSH Terms
AIDS Vaccines/administration & dosage,immunology Animals Antibodies, Viral/blood Gene Products, env/genetics,immunology HIV Antibodies/blood HIV Infections/immunology,prevention & control,virology HIV-1/immunology Humans Immune Sera/immunology Immunization Macaca mulatta Neutralization Tests SAIDS Vaccines/administration & dosage,immunology Simian Acquired Immunodeficiency Syndrome Simian Immunodeficiency Virus/immunology env Gene Products, Human Immunodeficiency Virus
Chemicals
AIDS Vaccines Antibodies, Viral Gene Products, env HIV Antibodies Immune Sera SAIDS Vaccines env Gene Products, Human Immunodeficiency Virus gp140 envelope protein, Human immunodeficiency virus 1
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Derby Nina R
Seattle Biomedical Research Institute, WA 98109, USA.
Kraft Zane
Kan Elaine
Crooks Emma T
Barnett Susan W
Srivastava Indresh K
Binley James M
Stamatatos Leonidas
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
Published
2006-09-00
Pages
8745-62
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC1563892
Subset
IM
Grants
NIAID NIH HHS · T32 AI007509 · United States
NIAID NIH HHS · R01 AI047708 · United States
NIAID NIH HHS · R56 AI058763 · United States
NIAID NIH HHS · R01 AI058763 · United States
NIAID NIH HHS · R56 AI047708 · United States
NIAID NIH HHS · AI51217 · United States
NIAID NIH HHS · AI007509 · United States
NIAID NIH HHS · AI47708 · United States
NIAID NIH HHS · R01 AI051217 · United States
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