EBOV Protection Is Supported by T Cell-Dependent Humoral Responses But Is Not Requisite for Survival
Abstract
Despite agreement across Ebola virus (EBOV) vaccine platforms of a requisite role for antibody-dependent protection and extensive efforts in development of antibody therapy against lethal EBOV infection, the establishment of protective EBOV B cell responses has yet to be fully described. Previously, we demonstrated that vaccination of mice, guinea pigs, or nonhuman primates with virus-like particles (eVLP) expressing EBOV glycoprotein (GP) elicited full protection. More recently, we illustrated that inclusion of the Toll-like receptor 3 agonist and clinical grade adjuvant, Hiltonol, enhanced GP-specific antibody titers and durable EBOV protection. Here in, we outline that the cellular events mediating EBOV humoral responses are exclusively generated from T-cell dependent mechanisms. We show that Hiltonol both augmented and sustained eVLP-mediated GC B cell formation and increased antigen-specific B cell frequencies. In addition, we define the in-vivo requirement of T-cell follicular help and CD40-CD40L signaling in establishing EBOV GP antibody responses. Finally and unexpectedly, we demonstrate that while EBOV antibody responses can enhance protection, survival in the complete absence of antibodies can be achieved; however, B cells are obligate.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 03, 2016
- Accession Number
- AD1009884
Entities
People
- Christopher L. Cooper
- David Langan
- Jesse Steffens
- Karen A Martins
- Sabrina Stronsky
- Sean Van Tongeren
- Sina Bavari
Organizations
- United States Army Medical Research Institute of Infectious Diseases