Abstract
BackgroundAs HIV-specific cytotoxic T cells play a key role during acute and chronic HIV-1 infection in humans, the ability of potential anti-HIV vaccines to elicit strong, broad T cell responses is likely to be crucial. The HIV-1 Gag antigen is widely considered a relevant antigen for the development of an anti-HIV vaccine since it is one of the most conserved viral proteins and is also known to induce T cell responses. In the majority of studies reporting Gag-specific cellular immune responses induced by Gag-based vaccines, only a small number of Gag T cell epitopes were tested in preclinical mouse models, thus giving an incomplete picture of the numerous possible cellular immune responses against this antigen. As is, this partial knowledge of epitope-specific T cell responses directed to Gag will unavoidably result in a limited preclinical evaluation of Gag-based vaccines.ResultsIn this study we identified new Gag CD8+ T cell epitopes in BALB/c mice vaccinated with the HIV-1 Gag antigen alone or in combination with the HIV-1 Tat protein, which was recently shown to broaden T cell responses directed to Gag. Specifically, we found that CTL responses to Gag may be directed to nine different CTL epitopes, and four of these were mapped as minimal CTL epitopes.ConclusionThese newly identified CTL epitopes should be considered in the preclinical evaluation of T cell responses induced by Gag-based vaccines in mice.
Highlights
As HIV-specific cytotoxic T cells play a key role during acute and chronic HIV-1 infection in humans, the ability of potential anti-HIV vaccines to elicit strong, broad T cell responses is likely to be crucial
We have recently reported that vaccines based on a combination of the HIV-1 Tat protein with heterologous antigens induce broader T cell responses against the coadministered antigen, thereby indicating Tat as a useful tool in the development of novel vaccination strategies against AIDS [7,8,9]
In order to expand our limited knowledge of epitope-specific T cell responses directed to a given antigen, the aim of this study was to identify the repertoire of CD8+ T cell epitopes of the HIV-1 Gag antigen in BALB/c mice vaccinated with the HIV-1 Gag protein
Summary
As HIV-specific cytotoxic T cells play a key role during acute and chronic HIV-1 infection in humans, the ability of potential anti-HIV vaccines to elicit strong, broad T cell responses is likely to be crucial. In the majority of studies reporting Gag-specific cellular immune responses induced by Gag-based vaccines, only a small number of Gag T cell epitopes were tested in preclinical mouse models, giving an incomplete picture of the numerous possible cellular immune responses against this antigen. Several studies have indicated that HIV-specific T cell responses play a key role in limiting the progression of acute and chronic infection in humans [4,5], and that long-term non-progressors have consistently higher levels (page number not for citation purposes). As the HIV-1 Gag antigen is one of the most conserved viral proteins, and is known to induce T cell responses, both in animal models and in humans, it is widely considered a relevant antigen for the development of an antiHIV vaccine. Previous studies have shown that Gag-specific T cell responses contribute to clear primary viremia and control later viral replication, thereby slowing progression of the disease [4,10,11,12]
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