Antigenic competition affects the magnitude and breadth of CD8 T cell immunity following immunization with a nanoparticle neoantigen cancer vaccine

Abstract

Abstract Induction of T cell immunity against neoantigens of cancers is a promising personalized vaccine approach against tumors. We developed a novel vaccine platform to enhance the breadth and magnitude of neoantigen-specific CD8 T cell responses by coupling neoantigen peptides to a polymer containing a Toll-Like Receptor-7/8 agonist that self-assembles into nanoparticles (termed SPP-7/8a). As the SPP-7/8 vaccine platform can be formulated to immunize against multiple neoantigen peptides, a critical issue is how the delivery influences the magnitude and breadth of CD8 T cell responses. Thus, C57BL/6 mice were injected subcutaneously against a single neoantigen at either a single site, or divided across four sites. CD8 T cell responses were ~3% in the mice immunized at multiple sites compared to ~1% at a single injection site. To assess breadth, mice were immunized with four antigens, with either a single antigen at each of four injection sites or a combination of all four antigens across four injection sites. In mice that received all four antigens in each site, CD8 T cell responses against two of the antigens were undetectable. By contrast, in animals that received 1 antigen per site, responses were detected against all four antigens, and the total magnitude was higher than animals receiving 4 antigens per site. Collectively, these data suggest that despite increasing the CD8 T cell response of a single antigen via multi-site injection, vaccination even with as few as 4 antigens can interfere with the induction of neoantigen-specific CD8 T cells. Current work is focused on altering the delivery of the SPP-7/8a immunization approach to optimize both magnitude and breadth of CD8 T cell immunity that will be critical for tumor treatment and protection.