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Vaccine Strategies for Combined Targeting of Innate and Adaptive Immune Pathways

Final Report Summary - VaccTIP (Vaccine Strategies for Combined Targeting of Innate and Adaptive Immune Pathways)

Successful vaccination against human immunodeficiency virus (HIV) infection is a major challenge for public health. In light of recent clinical trials, it appears necessary to develop new strategies for improving the magnitude and broadening the immune response against the virus. The current HIV-specific candidate vaccines are mainly aimed at targeting cellular immunity and have a limited immunogenicity restricted to a few epitopes. Therefore, new vaccines that stimulate stronger and broader T cell responses as well as neutralising antibodies need to be developed. Recent advances emphasised the key role of innate immunity pathways in the stimulation of effective adaptive immune responses.

'Vaccine strategies for combined targeting of innate and adaptive immune pathways' (VaccTIP) proposed to assess different approaches that activate the innate immune system in order to selectively trigger, enhance and shape cellular and humoral neutralising responses. Its specific aims were to:

- produce polymeric CD40L (Mega-CD40L) and bacterial Flagellin as two novel adjuvants targeting the innate and adaptive immune pathways;
- construct novel alphavirus based-vaccine vectors which stimulate innate immunity and will further elevate humoral and cellular immune responses and to bring the technology forward in view of future implementation as global vaccines in developing countries;
- analyse innate immune reactions both in human and murine settings;
- evaluate the effect on T and B cell responses to specific antigens in human and murine models;
evaluate the adjuvanticity on recombinant alpha- and poxvirus vectors expressing HIV-1 antigens.