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Journal of Virology, September 2006, p. 8745-8762, Vol. 80, No. 17
0022-538X/06/$08.00+0     doi:10.1128/JVI.00956-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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{dagger}

Nina R. Derby,1,2 Zane Kraft,1 Elaine Kan,3 Emma T. Crooks,4 Susan W. Barnett,3 Indresh K. Srivastava,3 James M. Binley,4 and Leonidas Stamatatos1,2*

Seattle Biomedical Research Institute, Seattle, Washington 98109,1 Department of Pathobiology, University of Washington, Seattle, Washington 98109,2 Vaccines Research, Chiron Corporation, Emeryville, California 94608,3 Torrey Pines Institute for Molecular Studies, San Diego, California 921214

Received 10 May 2006/ Accepted 20 June 2006

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, SHIVSF162P4, and humans infected with heterologous HIV-1 isolates. Four gp140 immunogens were evaluated: SF162gp140, {Delta}V2gp140 (lacking the crown of the V2 loop), {Delta}V3gp140 (lacking the crown of the V3 loop), and {Delta}V2{Delta}V3gp140 (lacking both the V2 and V3 loop crowns). SF162gp140 and {Delta}V2gp140 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 {Delta}V2gp140 but were weak in potency and narrow in specificity. No heterologous NAbs were elicited by {Delta}V3gp140 or {Delta}V2{Delta}V3gp140. In contrast, the SHIVSF162P4-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.

* Corresponding author. Mailing address: Seattle Biomedical Research Institute, 307 Westlake Avenue North, Seattle, WA 98109. Phone: (206) 256-7200. Fax: (206) 256-7229. E-mail: leo.stamatatos{at}sbri.org.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, September 2006, p. 8745-8762, Vol. 80, No. 17
0022-538X/06/$08.00+0     doi:10.1128/JVI.00956-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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