1. Adjuvant-enhanced CD4 T Cell Responses are Critical to Durable Vaccine Immunity.
- Author
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Martins KAO, Cooper CL, Stronsky SM, Norris SLW, Kwilas SA, Steffens JT, Benko JG, van Tongeren SA, and Bavari S
- Subjects
- Adoptive Transfer, Animals, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, CD4-Positive T-Lymphocytes metabolism, Cytokines metabolism, Disease Models, Animal, Ebolavirus immunology, Female, Hemorrhagic Fever, Ebola mortality, Hemorrhagic Fever, Ebola prevention & control, Immunization, Immunoglobulin G immunology, Lymphocyte Count, Models, Animal, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, Vaccines administration & dosage, Vaccines, Virus-Like Particle immunology, Adjuvants, Immunologic, CD4-Positive T-Lymphocytes immunology, Immunity, Vaccines immunology
- Abstract
Protein-based vaccines offer a safer alternative to live-attenuated or inactivated vaccines but have limited immunogenicity. The identification of adjuvants that augment immunogenicity, specifically in a manner that is durable and antigen-specific, is therefore critical for advanced development. In this study, we use the filovirus virus-like particle (VLP) as a model protein-based vaccine in order to evaluate the impact of four candidate vaccine adjuvants on enhancing long term protection from Ebola virus challenge. Adjuvants tested include poly-ICLC (Hiltonol), MPLA, CpG 2395, and alhydrogel. We compared and contrasted antibody responses, neutralizing antibody responses, effector T cell responses, and T follicular helper (Tfh) cell frequencies with each adjuvant's impact on durable protection. We demonstrate that in this system, the most effective adjuvant elicits a Th1-skewed antibody response and strong CD4 T cell responses, including an increase in Tfh frequency. Using immune-deficient animals and adoptive transfer of serum and cells from vaccinated animals into naïve animals, we further demonstrate that serum and CD4 T cells play a critical role in conferring protection within effective vaccination regimens. These studies inform on the requirements of long term immune protection, which can potentially be used to guide screening of clinical-grade adjuvants for vaccine clinical development.
- Published
- 2015
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