Interference of Elicited Immunity to HIV-1 Gagp55 by Envgp120, but Not by Influenza HA, During Co-immunizations

Abstract

Immunization with more than one immunogen (coimmunization) is an efficient regimen to induce immunity to multiple antigens. However, immune interference has been reported using multi-plasmid DNA immunizations (e.g. co-immunization using HIV-1 Gag-Polp160 and Vpr). HIV-1 envelope (Env) and Gag gene products are the most predominant immunogens used in current AIDS vaccines, although, few studies have evaluated possible immune interference when these two antigens are coadministered. Therefore, in this study, immune interference during co-inoculation was examined using DNA vaccines expressing Envgp120 and Gagp55 from gene sequences optimized for efficient expression in mammalian cells (codon-optimized). BALB/c mice vaccinated with each plasmid individually elicited high titer immune responses, however, when these same plasmids were coinoculated, there was a reduction in the immunity elicited to Gagp55. In contrast, anti-Envgp120 immunity was not affected. To determine if the anti-Gag immune interference was specific to Env, mice were co-immunized with plasmids expressing a soluble form of hemagglutinin (sHA) from influenza virus (A/PR/8/34) and Gagp55DNA. Similar titers of anti-Gagp55 immunity were observed in mice co-immunized with sHA-DNA and Gagp55-DNA, as mice vaccinated with Gagp55-DNA only. Gagp55-DNA co-immunization did not affect anti-Envgp120 or anti-sHA immune responses. The Envgp120/Gagp55 immune interference elicited during co-immunizations was not dependent on the amount of protein expressed. In addition, this induced immune interference was observed in mice even when the immunizations were performed in separate locations. Therefore, Envgp120 specifically interferes with the elicitation of anti-Gagp55 immune responses following co-immunization. Since Env and Gag are the most commonly used HIV-1 antigens in AIDS vaccine designs, future vaccine development should consider the effect of each immunogen during evaluation of the effectiveness of AIDS vaccines. from 2005 International Meeting of The Institute of Human Virology Baltimore, USA, 29 August – 2 September 2005