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A recombinant adenovirus-based vector elicits a specific humoral immune response against the V3 loop of HIV-1 gp120 in mice through the “Antigen Capsid-Incorporation” strategy

Linlin Gu1, Valentina Krendelchtchikova1, Alexandre Krendelchtchikov1, Robert A Oster2, Kohtaro Fujihashi3 and Qiana L Matthews14*

Author Affiliations

1 Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, 845 19th Street South, Birmingham, AL 35294, USA

2 Department of Medicine, Division of Preventive Medicine, University of Alabama at Birmingham, 1717 11th Avenue South, Birmingham, AL 35294, USA

3 Department of Pediatric Dentistry, The Immunobiology Vaccine Center, The Institute of Oral Health Research, The University of Alabama at Birmingham, Birmingham, AL 35294, USA

4 Center for AIDS Research, University of Alabama at Birmingham, Birmingham, AL 35294, USA

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Virology Journal 2014, 11:112  doi:10.1186/1743-422X-11-112

Published: 16 June 2014

Abstract

Background

Due to potential advantages, human adenoviral vectors have been evaluated pre-clinically as recombinant vaccine vectors against several cancers and infectious diseases, including human immunodeficiency virus (HIV) infection. The V3 loop of HIV-1 glycoprotein 120 (gp120) contains important neutralizing epitopes and plays key roles in HIV entry and infectivity.

Methods

In order to investigate the humoral immune response development against portions of the V3 loop, we sought to generate four versions of adenovirus (Ad)-based V3 vectors by incorporating four different antigen inserts into the hypervariable region 1 (HVR1) of human adenovirus type 5 (hAd5) hexon. The strategy whereby antigens are incorporated within the adenovirus capsid is known as the “Antigen Capsid-Incorporation” strategy.

Results

Of the four recombinant vectors, Ad-HVR1-lgs-His6-V3 and Ad-HVR1-long-V3 had the capability to present heterologous antigens on capsid surface, while maintaining low viral particle to infectious particle (VP/IP) ratios. The VP/IP ratios indicated both high viability and stability of these two vectors, as well as the possibility that V3 epitopes on these two vectors could be presented to immune system. Furthermore, both Ad-HVR1-lgs-His6-V3 and Ad-HVR1-long-V3 could, to some extent escape the neutralization by anti-adenovirus polyclonal antibody (PAb), but rather not the immunity by anti-gp120 (902) monoclonal antibody (MAb). The neutralization assay together with the whole virus enzyme-linked immunosorbent assay (ELISA) suggested that these two vectors could present V3 epitopes similar to the natural V3 presence in native HIV virions. However, subsequent mice immunizations clearly showed that only Ad-HVR1-lgs-His6-V3 elicited strong humoral immune response against V3. Isotype ELISAs identified IgG2a and IgG2b as the dominant IgG isotypes, while IgG1 comprised the minority.

Conclusions

Our findings demonstrated that human adenovirus (hAd) vectors which present HIV antigen via the “Antigen Capsid-Incorporation” strategy could successfully elicit antigen-specific humoral immune responses, which could potentially open an avenue for the development of Ad-based HIV V3 vaccines.

Keywords:
Adenovirus (Ad); Human adenovirus (hAd); “Antigen Capsid-Incorporation” strategy; HIV V3 loop; Humoral immune response; IgG isotype; Neutralization