A new strategy for the induction of specific CD 4 + and CD 8 + cellular responses against a recombinant multiepitopic protein of HIV-1 @

Modern vaccine development usually requires highly purified recombinant proteins. However, these antigens in general are poorly immunogenic, and when administered in aluminum-based adjuvants –the only universally accepted formulationthe elicited response has a Th2 bias that is inadequate for immunizing against pathogens such as the Human Immunodeficiency Virus type 1 (HIV-1), whose control requires a vigorous cellular immune response. The purpose of this work was to obtain a strong cellular immune response specifically directed against a recombinant multiepitopic antigen that includes HIV-1 sequences of relevance to vaccine development. This was achieved by taking advantage of the adjuvanticity of the surface (HBsAg and S) and nucleocapsid (HBcAg and C) antigens of the hepatitis B virus (HBV) and using the parenteral and/or mucosal immunization routes. After immunizing mice with formulations containing these antigens, it was evidenced that the mixtures of the HIV-1-derived recombinant multiepitopic antigen (CR3) with the surface and nucleocapsid antigens from HBV generate a strong Th1-type response –detected by an increased secretion of IFNγ and the proliferation of CD4+ and CD8+ cells— after parenteral and nasal inoculations. Furthermore, it was shown that co-immunization through the nasal and parenteral routes generates more potent immune responses than parenteral delivery alone; and that a pre-existing specific response against HBV antigens does not inhibit the development of a strong CR3-specific CD4+ and CD8+ cellular responses.