Antibody Repertoires to the Same Ebola Vaccine Antigen Are Differentially Affected by Vaccine Vectors

Abstract

SUMMARY Comparative immune response profiling is important for selecting next-generation vaccines. We comprehensively evaluated the antibody responses from a panel of nine respiratory vaccines against Ebola virus (EBOV) derived from human and avian paramyxoviruses expressing EBOV glycoprotein (GP). Most vaccines were protective in guinea pigs but yielded antibody repertoires that differed in proportion targeting key antigenic regions, avidity, neutralizing antibody specificities, and linear epitope preferences. Competition studies with monoclonal antibodies from human survivors revealed that some epitopes in GP targeted for neutralization were vector dependent, while EBOV-neutralizing titers correlated with the response magnitude toward the receptor-binding domain and GP1/GP2 interface epitopes. While an immunogen determines the breadth of antibody response, distinct vaccine vectors can induce qualitatively different responses, affecting protective efficacy. These data suggest that immune correlates of vaccine protection cannot be generalized for all vaccines against the same pathogen, even if they use the exact same immunogen.

Ebola virus glycoprotein domains associated with protective efficacy

“…In summary, our data support and expand existing data sets about the importance of antibodies directed to the EBOV GP GC for protection from EVD [31,32,38]. Our findings also demonstrate that both the GC and MLD are dispensable for VSV-EBOV-based vaccine vector replication in vitro .…”

“…Little is known, however, about the influence of pre-existing immunity to EBOV or EBOV GP on vaccine efficacy using VSV-EBOV or VSV-EBOV-based vaccine candidates. Vaccination utilizing EBOV GP has previously been shown to elicit antibodies predominantly targeting the GC and MLD [31,32]. These antibodies are generally non-neutralizing as both domains get cleaved off during EBOV entry into cells before receptor binding and fusion occurs [33].…”

Surface chemistry of gold nanoparticles for health-related applications

“…The efficiency of a vaccine is highly dependent on the vector effect. 18 Antigen-AuNP conjugates, as alternative display vectors to produce highly effective and safe vaccines, show advanced perspectives of greater synthetic control and higher density than on current vector materials such as proteins, peptides/lipopeptides and dendrimers. 19,20 Besides, these materials other than gold may cause immune responses and produce undesired antibodies which decreases the efficiency of vaccinations.…”

Ebola vaccine–induced protection in nonhuman primates correlates with antibody specificity and Fc-mediated effects

“…Previously, we developed a panel of nine respiratory virus-vectored vaccines, based on human and avian paramyxoviruses (APMVs), expressing the glycoprotein (GP) of EBOV, and tested them in a guinea pig challenge model (18). The panel was narrowed down to the five vectors that conferred 100% protection and elicited highmagnitude responses against a broader spectrum of GP antigenic regions.…”