1. T-cell-dependent mechanisms promote Ebola VLP-induced antibody responses, but are dispensable for vaccine-mediated protection
- Author
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Cooper, Christopher L, Martins, Karen A, Stronsky, Sabrina M, Langan, David P, Steffens, Jesse, Van Tongeren, Sean, and Bavari, Sina
- Subjects
B-Lymphocytes ,T-cell dependent antibody ,T-Lymphocytes ,Hemorrhagic Fever, Ebola ,Antibodies, Viral ,Ebolavirus ,Germinal Center ,virus-like particle ,Disease Models, Animal ,Mice ,adjuvant ,Adjuvants, Immunologic ,germinal center B-cell ,vaccine ,Ebola ,Animals ,Original Article ,Vaccines, Virus-Like Particle ,Ebola Vaccines ,RNA, Double-Stranded - Abstract
Humoral responses are essential for the protective efficacy of most Ebola virus (EBOV) candidate vaccines; however, the in vivo development of protective anti-EBOV B-cell responses is poorly defined. Here, by using the virus-like particle (VLP) as a model antigen, we demonstrate that humoral responses are generated through follicular B-cell and T-cell-dependent mechanisms in a mouse model of EBOV infection. In addition, we show that the inclusion of the clinical-grade dsRNA adjuvant known as poly-ICLC in VLP vaccinations both augments and sustains germinal center B-cell reactions, antigen-specific B-cell frequencies and anti-EBOV serum titers. Finally, we used mice that were deficient in either B-cells or T-cell-dependent antibody production to distinguish the contributing roles of EBOV humoral responses. We demonstrate that while anti-EBOV antibody responses promote protection, VLP-vaccinated mice can survive EBOV infection in the absence of detectable anti-EBOV antibodies. Moreover, we found that adjuvant signaling could circumvent the complete requirement for B-cell immunity in protection against EBOV. Collectively, these studies may prove valuable for the characterization and future development of additional EBOV vaccine candidates.
- Published
- 2017