Abstract
Using adjuvants to drive features of T cell responses to vaccine antigens is an important technological challenge in the design of new and improved vaccines against infections. Properties such as T helper cell function, T cell memory, and CD8+ T cell cytotoxicity may play critical roles in optimal and long-lived immunity through vaccination. Directly manipulating specific immune activation or antigen delivery pathways with adjuvants may selectively augment desired T cell responses in vaccination and may improve the effectiveness and durability of vaccine responses in humans. In this review we outline recently studied adjuvants in their potential for antigen presenting cell and T cell programming during vaccination, with an emphasis on what has been observed in studies in humans as available.
Highlights
Adjuvants are substances that enhance the immune response to a vaccine
In mice immunized with Ebola virus glycoprotein, the Matrix-M adjuvant, derived from mixing 2 specific ISCOMATRIX types, was demonstrated to significantly enhance production of antigen specific CD8+ T cells responses, compared to Ebola virus glycoprotein vaccine adjuvanted with alum, or with no adjuvant [25]
The disruption of T follicular helper (Tfh) cell responses is associated with an impaired antibody response to infection or vaccination in numerous models [61], and enhancement of Tfh production in vaccination correlates with improved B cell memory in response to vaccination [62]
Summary
Adjuvants are substances that enhance the immune response to a vaccine. Adjuvants may occur naturally as part of a vaccine, as seen in the pathogen associated molecular patterns (PAMPs) contained in live-attenuated vaccines or may be added to a vaccine preparation to enhance immune responses. In mice immunized with Ebola virus glycoprotein, the Matrix-M adjuvant, derived from mixing 2 specific ISCOMATRIX types (as described in [24]), was demonstrated to significantly enhance production of antigen specific CD8+ T cells responses, compared to Ebola virus glycoprotein vaccine adjuvanted with alum, or with no adjuvant [25] In this model, multifunctional CD8+ T cells, here CD8+ T cells simultaneously producing two or three of the cytokines, TNF-α, IL-2, or IFN-γ, were observed at increased frequencies if Ebola glycoprotein antigen was administered with Matrix-M, and occurred in a MatrixM dose-dependent manner. In a murine model of live attenuated influenza vaccination, treatment with poly(I:C) after vaccination led to increased dendritic cell activation and increased CD8+ T cell responses within the lung [60] These observations underscore the potential of CpG and poly(I:C) as adjuvants in enhancing multifunctional, antigen-specific CD8+ T cell responses at systemic sites, and at the mucosa. Elicitation of antigen-specific CD8+ T cells, trafficking of antigen into pathways for MHC I expression
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