Novel Adjuvant Systems that Generate Pathogen Specific T Cell Responses Following Immunization for Infectious Disease Vaccine Formulations

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Background

Adjuvants are an essential component of subunit vaccine formulations and are gaining wider experimental use in attenuated and nucleic acid vaccine formulations. Adjuvants increase the immunogenic response to the immunizing antigens or agent and can influence the type of immune response to vaccination. First generation adjuvants, including alum and squalene oil-in-water emulsions, function as antigen delivery systems by creating depots of trapped antigen at the injection site. This class of adjuvants is widely available for vaccine formulations and have been approved for use in many licensed vaccines. Second generation adjuvants are ligands for pathogen-associated molecular pattern (PAMP) recognition receptors, such as Toll-like receptors (TLRs), that activate antigen presenting cells through their cognate receptor. Although the FDA has begun approving new adjuvants beyond first generation systems, such as TLR agonists, there remains a paucity of T cell stimulating adjuvanting agents available for use in human vaccine formulations. As a result, there is still a lack of effective vaccine candidates for many pathogens that require a cellular immune response for protection.

Despite the robust and protective immune responses elicited by whole-organism vaccines, this technology is not relevant for every infectious pathogen requiring a vaccine. For some pathogens the risk of reactivation makes them too dangerous to be given as a whole organism vaccine formation, and others can be easily weaponized as bioterrorism agents and therefore cannot be realistically scaled up for the purpose of immunization. Still, other whole-organism vaccine formulations elicit far too robust immune responses to be safe. Subunit vaccines offer safe solutions to each of these issues. However, subunit vaccines require the inclusion of an adjuvant to generate an immunogenic response to immunization. The status quo as it pertains to adjuvant formulation in subunit vaccine development is to use adjuvanting agents that preferentially skew towards humoral responses and away from cellular responses to the immunizing antigens. For some pathogens, robust humoral responses to immunization are sufficient to provide protection upon exposure with the pathogenic organism. However, many pathogens, including bacterial species like Coxiella burnetii and Mycobacterium tuberculosis, require effective cellular responses for protection against challenge. Interestingly, many of these pathogens, including several neglected tropic diseases and bioterrorism agents, are still lacking effective vaccines, underscoring the need for a better knowledge of adjuvants that generate T cell responses, and an expanded understanding of the mechanisms through which adjuvants that stimulate cellular immune responses confer protection.

Several significant innovations and advances have been made in the field of T cell stimulating adjuvant systems, including STING agonists and nanoparticles, yet these systems are not widely used in approved vaccine formulations, despite the immediate impact these adjuvants could have on human health and disease prevention.

The goal of this collection is to expand the field’s understanding the immunological mechanisms behind T cell stimulating adjuvant systems and how they confer protective efficacy in vaccine formulations.

We welcome the submission of Original Research, Review, Mini Review and prospective articles focusing on, but not limited to, the following themes:
• Immunological mechanisms of protection for T cell stimulating adjuvant systems
• Novel adjuvant systems that stimulate cellular immune responses to immunization
• Immunological requirements of vaccine systems to elicit T cell dominated immune responses
• Therapeutic challenges and benefits of the increased use of T cell stimulating adjuvant systems in infectious disease vaccines
• Protective benefit of combining humoral and cellular skewing adjuvants in the same infectious disease vaccine formulations to increase vaccine efficacy
• Impact that T cell stimulating adjuvant systems could have on reducing global infectious disease burden

Keywords: Vaccine, adjuvant, cellular response to immunization, infectious disease, T cell response to immunization, intracellular infection

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