T Cell Vaccinology: Beyond the Reflection of Infectious Responses

Abstract

Inducing sustained, robust CD8+ T cell responses is necessary for therapeutic intervention in chronic infectious diseases and cancer. Unfortunately, most adjuvant formulations fail to induce substantial cellular immunity in humans. Attenuated acute infectious agents induce strong CD8+ T cell immunity, and are thought to therefore represent a good road map for guiding the development of subunit vaccines capable of inducing the same. However, recent evidence suggests that this assumption may need reconsideration. Here we provide an overview of subunit vaccine history as it pertains to instigating T cell responses. We argue that in light of evidence demonstrating that T cell responses to vaccination differ from those induced by infectious challenge, research in pursuit of cellular immunity-inducing vaccine adjuvants should no longer follow only the infection paradigm.

Dendritic cell and antigen dispersal landscapes regulate T cell immunity

“…Our findings are of significant relevance to vaccine development, providing a mechanistic understanding of how antigen dispersal influences innate and adaptive immune responses. Subunit protein vaccines have generally failed to yield protective CD8 + T cell immunity, although still generating competent CD4 + T cell and humoral responses ( Koup and Douek, 2011 ; Pennock et al, 2016 ). In addition to previous indications that soluble antigens are inefficiently targeted to the cross-presentation pathway, our data now reveal that the relatively poor capacity of administered protein antigens to reach the DCs specialized in cross-presentation is a major limiting step in generation of potent CD8 + T cell immunity.…”

IL-27p28 Production by XCR1+ Dendritic Cells and Monocytes Effectively Predicts Adjuvant-Elicited CD8+ T Cell Responses

“…Precisely why an adjuvanted subunit vaccine diverges so dramatically from the infectious response with regard to its dependency on IL-27 is still under investigation. Regardless, it serves to highlight the fact that T cell responses to infectious challenge are controlled by different mechanisms than those produced in response to vaccine adjuvants ( 49 ). The data that we present in this article show that IL-27 is central to the induction of cellular immunity to subunit vaccination, as well as highly predictive of the resulting overall magnitude of immunity achieved.…”

CD70 encoded by modified vaccinia virus Ankara enhances CD8 T‐cell‐dependent protective immunity in MHC class II‐deficient mice

“…Due to its replication deficiency in mammalian hosts, however, it can also be regarded as a subunit vaccine in which the subunit antigen is genetically encoded instead of being provided as protein. This balancing act can have manifold consequences on the mechanistic requirements for MVA‐induced T‐cell responses, as recently reviewed by Pennock et al 55. As pointed out in this and other reviews, the CD27/CD70 pathway of co‐stimulation has been shown in many vaccination, infection and cancer therapy settings to be crucial for the development, differentiation and maintenance of CD8 T‐cell responses55, 56, 57 and so has become a therapy target in humans 58.…”