Human AIDS Vaccines: Mice Offer Shortcut

R. Weiss

doi:10.2307/3974638

Development of a BCG Recombinant Vehicle for Candidate AIDS Vaccines

International Reviews of Immunology ◽

10.3109/08830189009061766 ◽

1990 ◽

Vol 7 (1) ◽

pp. 79-83 ◽

Cited By ~ 11

Author(s):

Anna Aldovini ◽

Richard A. Young

Keyword(s):

Aids Vaccines

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Modeling AIDS vaccines: the cellular level

Memórias do Instituto Oswaldo Cruz ◽

10.1590/s0074-02761992000100017 ◽

1992 ◽

Vol 87 (1) ◽

pp. 103-113 ◽

Cited By ~ 2

Author(s):

Claudio J. Struchiner ◽

M. Elizabeth Halloran

Keyword(s):

Cellular Level ◽

Aids Vaccines

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X4 Human Immunodeficiency Virus Type 1 gp120 Down-Modulates Expression and Immunogenicity of Codelivered Antigens

Journal of Virology ◽

10.1128/jvi.00394-09 ◽

2009 ◽

Vol 83 (21) ◽

pp. 10941-10950 ◽

Cited By ~ 10

Author(s):

Avi-Hai Hovav ◽

Michael Santosuosso ◽

Maytal Bivas-Benita ◽

Andre Plair ◽

Alex Cheng ◽

...

Keyword(s):

Immune Response ◽

Human Immunodeficiency Virus ◽

Antigen Presentation ◽

Antigen Expression ◽

V3 Loop ◽

Humoral Immune ◽

Immunodeficiency Virus ◽

Aids Vaccines ◽

Hiv 1

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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