CONICET | Buscador de Institutos y Recursos Humanos

There is a need of adjuvants which can improve cellular immune responses of influenza vaccines. One interesting approach is to test different adjuvants in order to obtain enhanced Th1 immune response. Montanide 70VG is a water in oil adjuvant which has been used in numerous experimental veterinary vaccines. This adjuvant is good to induce humoral immune responses, but little is known about the ability to induce cellular immune responses. In this work, we explored the properties of the Montanide 70VG, and in combination with the Poly(I:C) adjuvant, in order to enhance Th1 immunity of a universal influenza vaccine based on the recombinant nucleoprotein of influenza (rNP). We developed a vaccine formulated with rNP in combination with: the traditional incomplete Freund´s adjuvant (IFA), Montanide 70 VG, Poly (I:C), and Montanide 70 VG+Poly (I:C). The vaccine was administered in mice and humoral and cellular immune responses induced by the adjuvanted and non-adjuvanted vaccinations were evaluated. We found that combining Montanide 70 VG + Poly (I:C) adjuvants improved the Th1-skewed antigen-specific immune response. Vaccinated mice with the adjuvants combination developed the highest antibodies NP-specific titers of IgG. Interestingly, the use of Montanide 70 VG, in Montanide alone formulation as well in TLR3 combination, improved specifically IgG2b and IgG2c antibodies titers. In the contrast, the use of IFA adjuvant induced mainly IgG1 titer. In addition, vaccinated mice with Montanide 70 VG+Poly (I:C) showed a Th1?skewed response evidenced by a high frequency of IFN-γ-secreting CD4 T cells and also cytotoxic response evidenced by a high frequency of IFN-γ-secreting CD8 T cells by flow cytometry. Our data demonstrated that rNP with Montanide 70VG plus TLR 3 agonist combination, is able to induce mainly a Th1-immunity, which is highly in demand to induce efficient immune responses against influenza.