Virology, Nebraska Center for

 

Authors

Avi-Hai Hovav, Institute of Dental Sciences, Hebrew University-Hadassah School of Dental Medicine, Jerusalem, IsraelFollow
Michael Santosuosso, AIDS Research Center, Department of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts
Maytal Bivas-Benita, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
Andre Plair, AIDS Research Center, Department of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts
Alex Cheng, AIDS Research Center, Department of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts
Mazal Elnekave, Institute of Dental Sciences, Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
Elda Righi, AIDS Research Center, Department of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts
Tao Chen, AIDS Research Center, Department of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts
Satoshi Kashiwagi, AIDS Research Center, Department of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts
MIchael W. Panas, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
Shi-Hua Xiang, University of Nebraska-LincolnFollow
Karina Furmanov, Institute of Dental Sciences, Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
Norman L. Letvin, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
Mark C. Poznansky, Department of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts

Date of this Version

2009

Citation

Journal of Virology, Nov. 2009, p. 10941–10950 Vol. 83, No. 21

Comments

Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Abstract

In order to increase the immune breadth of human immunodeficiency virus (HIV) vaccines, strategies such

as immunization with several HIV antigens or centralized immunogens have been examined. HIV-1 gp120

protein is a major immunogen of HIV and has been routinely considered for inclusion in both present and

future AIDS vaccines. However, recent studies proposed that gp120 interferes with the generation of immune

response to codelivered antigens. Here, we investigate whether coimmunization with plasmid-encoded gp120

alters the immune response to other coadministered plasmid encoded antigens such as luciferase or ovalbumin

in a mouse model. We found that the presence of gp120 leads to a significant reduction in the expression level

of the codelivered antigen in vivo. Antigen presentation by antigen-presenting cells was also reduced and

resulted in the induction of weak antigen-specific cellular and humoral immune responses. Importantly,

gp120-mediated immune interference was observed after administration of the plasmids at the same or at

distinct locations. To characterize the region in gp120 mediating these effects, we used plasmid constructs

encoding gp120 that lacks the V1V2 loops (­ ΔV1V2) or the V3 loop (ΔV3). After immunization, the ΔV1V2, but

not the ΔV3 construct, was able to reduce antigen expression, antigen presentation, and subsequently the

immunogenicity of the codelivered antigen. The V3 loop dependence of this phenomenon seems to be limited

to V3 loops known to interact with the CXCR4 molecule but not with CCR5. Our study presents a novel

mechanism by which HIV-1 gp120 interferes with the immune response against coadministered antigen in a

polyvalent vaccine preparation.

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