Identification of new HIV-1 Gag-specific cytotoxic T lymphocyte responses in BALB/c mice

Abstract

Background: 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. 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.

The HIV-1 Tat Protein Induces the Activation of CD8+ T Cells and Affects In Vivo the Magnitude and Kinetics of Antiviral Responses

“…Specifically, Balb/c mice were immunized with the HIV-1 Gag protein alone or in combination with Tat and, ten days after immunization, fresh splenocytes from immunized mice were assayed by IFNγ Elispot to evaluate T cell responses directed against previously identified Gag-derived peptides [31] containing eight CD8 epitopes (Table S1). As shown in Figure 1C, immunization with Gag alone did not induce detectable Gag-specific T cell responses, whereas immunization with the Gag protein in the presence of Tat elicited significant Gag-specific responses directed against all tested CD8 epitopes.…”

HIV-1 Tat-Based Vaccines: An Overview and Perspectives in the Field of HIV/AIDS Vaccine Development

“…Similarly, mice vaccinated with Env or with V2-deleted Env in combination with Tat responded to 17 peptides, 12 more than mice vaccinated with the Env proteins alone. The effect was specific as Tat did not affect Th2-type responses to these structural HIV proteins [97,214]. In contrast with these results, using a DNA vaccination approach Agwale and co-worker reported that vaccination with a bi-cistronic gp120-tat DNA diminished IFN-γ CD8+ T cell responses against the immunodominant HIV-1 gp120 Env peptide in mice compared to those induced by vaccination with DNA encoding gp120 alone and that the effect of Tat was abolished by a sequence deletion (aa 31-50) in the cys-core domain of Tat (2).…”

“…These combined vaccines should be more efficacious because they may attack the virus on early and late gene products. In these studies, mice vaccinated subcutaneously with the HIV-1 Gag, Env, or V2-deleted Env protein antigens in combination with the biologically active Tat protein developed strong humoral and cellular (Th1-and Th2-type) immune responses against Tat and the co-administered antigen and broadened the Th1-type and CTL responses against Gag or Env antigens [97,214]. In addition, these strategies were safe, immunogenic, and effective in containing SHIV 89.6P replication in cynomolgus macaques [Ensoli et al, manuscript in preparation], and based on these preclinical results, a Tat/V2-deleted Env protein vaccine will soon undergo phase I clinical trial testing in Italy (http://www.hiv1tat-vaccines.info/).…”

Identification and characterization of HLA-A*0301 epitopes in HIV-1 gag proteins using a novel approach

“…CTLs play an important role in host defense against HIV-1 by recognizing and eliminating infected cells (Cellini et al, 2008; Kitano et al, 2008; Westrop et al, 2009; Bangham, 2009). Identification of CTL epitopes correlated to immune protection is important for the development of vaccines that enhance T cell-mediated immune responses.…”

“…It is one of the most conserved viral proteins in HIV-1 and it is known to induce protective T-cell responses in animal models and in humans, making it a good candidate for development of an anti-HIV vaccine (Cellini et al, 2008; Kiepiela et al, 2004; Zuniga et al, 2006). Identification of CTL epitopes in this region is important and will help to understand host and virus interactions and contribute to vaccine development (Bangham, 2009).…”