Adjuvant-enhanced CD4 T Cell Responses are Critical to Durable Vaccine Immunity

• Main Authors: Karen A.O. Martins, Christopher L. Cooper, Sabrina M. Stronsky, Sarah L.W. Norris, Steven A. Kwilas, Jesse T. Steffens, Jacqueline G. Benko, Sean A. van Tongeren, Sina Bavari
• Format: Article
• Language: English
• Published: Elsevier 2016-01-01
• Series: EBioMedicine
• Subjects: Vaccine; Adjuvant; Durable protection; Immune correlates; Ebola virus
• Online Access: http://www.sciencedirect.com/science/article/pii/S2352396415302243

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.