Demonstration of Cross-Protective Vaccine Immunity against an Emerging Pathogenic Ebolavirus Species

PLoS Pathogens

Giulia Fabozzi¹  Clement Asiedu¹  Sabue Mulangu¹  Nancy J. Sullivan¹  Daphne Stanley¹  Michael Bailey¹  Richard A. Koup²  Mario Roederer²  Peter B. Jahrling³  Pierre E. Rollin⁴  Thomas G. Ksiazek⁴  Stuart T. Nichol⁴  Victoria Wahl-Jensen⁵  Lisa E. Hensley⁵  Joshua Johnson⁵  Anna N. Honko⁵ 

[1] Biodefense Research Section, Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, United States of America;Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, United States of America;Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America;Special Pathogens Branch, Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America;Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America

关键词: Vaccines;    Macaque;    T cells;    Immune response;    Cytotoxic T cells;    Viral vaccines;    Enzyme-linked immunoassays;    Cell-mediated immunity;   

DOI  :  10.1371/journal.ppat.1000904

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

A major challenge in developing vaccines for emerging pathogens is their continued evolution and ability to escape human immunity. Therefore, an important goal of vaccine research is to advance vaccine candidates with sufficient breadth to respond to new outbreaks of previously undetected viruses. Ebolavirus (EBOV) vaccines have demonstrated protection against EBOV infection in nonhuman primates (NHP) and show promise in human clinical trials but immune protection occurs only with vaccines whose antigens are matched to the infectious challenge species. A 2007 hemorrhagic fever outbreak in Uganda demonstrated the existence of a new EBOV species, Bundibugyo (BEBOV), that differed from viruses covered by current vaccine candidates by up to 43% in genome sequence. To address the question of whether cross-protective immunity can be generated against this novel species, cynomolgus macaques were immunized with DNA/rAd5 vaccines expressing ZEBOV and SEBOV glycoprotein (GP) prior to lethal challenge with BEBOV. Vaccinated subjects developed robust, antigen-specific humoral and cellular immune responses against the GP from ZEBOV as well as cellular immunity against BEBOV GP, and immunized macaques were uniformly protected against lethal challenge with BEBOV. This report provides the first demonstration of vaccine-induced protective immunity against challenge with a heterologous EBOV species, and shows that Ebola vaccines capable of eliciting potent cellular immunity may provide the best strategy for eliciting cross-protection against newly emerging heterologous EBOV species.

【 授权许可】

CC BY