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Authors
Abstract
Introduction: TERAVAC-HIV is a multiantigenic vaccine candidate against HIV-1 developed by the Center of Genetic Engineering and Biotechnology. This formulation includes three antigens: the recombinant HIV-derived quimeric protein CR3 comprising Th and CTL epitope rich regions from different viral proteins and the nucleocapsid (C) and surface (S) antigens of hepatitis B virus (HBV). Previous results demonstrated that subcutaneous administration in mice with TERAVAC in alum, elicits a Th1 immune response characterized by proliferation of CR3-specific CD4 and CD8 T cells and secretion of IFNg. In the present work, we evaluated the effect of co-adjuvation and co-administration of the HBV antigens in the aforementioned anti-CR3 response.
Materials and Methods: Balb/c mice were subcutaneously immunized with different antigenic mixtures of CR3 with each or both antigens of HBV in alum at anatomical distal sites. After the last immunization, CR3-specific immune response was assessed by IFNg ELISPOT and CFSE lymphoproliferation of CD8 T cells. Antibody response in sera and cytokine secretion in culture supernatant fluids were determined by ELISA.
Results: The coadjuvation of CR3 and C promoted the best CR3-specific Th1 immunodeviation. We observed anti-CR3 IFNg secretion in the absence of IL-4 and IL-10 and higher levels of IgG2a. In addition, CD8+ T cell proliferation was measured in response to CR3 antigen stimulation in vitro.
Conclusions: Although C and S contribute to TERAVAC immunogenicity, these results in mice suggest that non-covalent interactions between CR3 and C antigens during adjuvation are crucial to achieve the best CR3-specific Th1 immunodeviation.