Characterization of T cell responses induced by Flu SAM(NP)® and SAM(M1)® vaccines (VAC5P.1124)

Abstract

Vaccination remains the most cost-effective way to control Influenza outbreaks. However, current Influenza vaccines do not provide efficacious heterosubtypic immunity. Therefore, the development of a successful universal vaccination strategy is urgently needed. To achieve this goal, one approach is focused on the induction of a T cell based response versus more conserved flu antigens, such as the Nucleoprotein (NP) and the Matrix protein 1 (M1). The aim of this study was to evaluate the immunogenicity and protective efficacy conferred by conserved NP and M1 antigens expressed by a self-amplifying RNA-based vaccine (SAM(NP)® and SAM(M1)®). We demonstrate that SAM(NP)® and SAM(M1)® are immunogenic in Balb/c mice. SAM(NP)® formulation induced IFNγ+ and LAMP1+ NP-specific cytotoxic CD8+ T cells as well as multifunctional NP-specific CD4+ T cells. SAM(M1) ® elicited a robust polyfunctional CD4 T helper 1 response. Moreover, we show that SAM(NP)® and SAM(M1)® formulations, when administered separately or in combination, provided differential levels of protection against a lethal challenge with mouse-adapted A/PR/8/1934 (H1N1) Influenza virus. SAM(NP)® and SAM(M1)® formulation induced T cell immune responses, potent mediator of heterosubtypic immunity, therefore, they are promising antigens in the design of a cross-protective flu vaccine. Since the SAM® vaccine technology offers several advantages , it could potentially speed up the development of universal flu vaccine candidates.