Virology, Nebraska Center for
Date of this Version
2009
Citation
Journal of Virology, Nov. 2009, p. 10941–10950 Vol. 83, No. 21
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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