Antibody Repertoires to the Same Ebola Vaccine Antigen Are Differentially Affected by Vaccine Vectors
Michelle Meyer,
Asuka Yoshida,
Palaniappan Ramanathan,
Erica Ollmann Saphire,
Peter L. Collins,
James E. Crowe, Jr.,
Siba Samal,
Alexander Bukreyev
Affiliations
Michelle Meyer
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Galveston National Laboratory, Galveston, TX 77555, USA
Asuka Yoshida
Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, MD 20742, USA
Palaniappan Ramanathan
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Galveston National Laboratory, Galveston, TX 77555, USA
Erica Ollmann Saphire
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Peter L. Collins
RNA Virology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
James E. Crowe, Jr.
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics (Infectious Diseases), Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Siba Samal
Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, MD 20742, USA
Alexander Bukreyev
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Galveston National Laboratory, Galveston, TX 77555, USA; Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; Corresponding author
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. : Meyer et al. developed a panel of second-generation Ebola vaccines using respiratory viruses to deliver a common immunogen. The vaccines were protective against lethal infection in guinea pigs. The different vaccines elicited different antibody profiles, indicating correlates of protection may not be universal among Ebola vaccines. Keywords: Ebola, vaccine, mucosal, respiratory, immune correlates of protection, antibody profile
