Efficacy and safety of a modified vaccinia Ankara (MVA) vectored plague vaccine in mice

• Published in: Vaccine Vol. 28; no. 36; pp. 5891 - 5899
• Main Authors: Brewoo, Joseph N, Powell, Tim D, Stinchcomb, Dan T, Osorio, Jorge E
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 16.08.2010; Elsevier; Elsevier Limited
• Subjects: Allergy and Immunology; Animals; Antibodies; Antibodies, Bacterial - blood; Antigens, Bacterial - immunology; Applied microbiology; Bacterial diseases; Bacteriology; Biological and medical sciences; Disease; Encephalomyocarditis virus; Female; Fundamental and applied biological sciences. Psychology; Genomics; Human bacterial diseases; Infectious diseases; Medical sciences; Mice; Mice, Inbred BALB C; Mice, SCID; Microbiology; Miscellaneous; Modified vaccinia Ankara; Mortality; Plague; Plague - immunology; Plague - prevention & control; Plague Vaccine - immunology; Pore Forming Cytotoxic Proteins - immunology; Public health; Safety; Studies; Tropical bacterial diseases; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Synthetic - immunology; Vaccinia virus - immunology; Yersinia pestis; Yersinia pestis - immunology; United States > US; Plague; Modified vaccinia Ankara; Mice; Vaccines; Yersinia pestis; Rodentia; Vaccine; Infection; Vertebrata; Mammalia; Mouse; Efficiency; Viral disease; Bacteriosis; Bacteria; Vaccinia; Vector; Yersiniosis; Enterobacteriaceae
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2010.06.054

Abstract The efficacy and safety of plague vaccines based on the modified vaccinia Ankara (MVA) viral vector was evaluated. MVA recombinants were constructed expressing Yersinia pestis antigens under the translational control of the encephalomyocarditis virus (EMCV) internal ribosomal entry site (IRES) and/or fused to the tissue plasminogen activator (tPA) secretory signal. A MVA/ Y. pestis recombinant that expressed a truncated version of the low-calcium response V antigen (MVA/IRES/tPA/V307 ), conferred significant protection (87.5–100%) against intranasal or intraperitoneal challenge with CO92 (encapsulated) or Java 9 (non-encapsulated) strains of Y. pestis , respectively. In contrast, a MVA/ Y. pestis recombinant that expressed the full-length V antigen provided only 37.5% protection against challenge with CO92 or Java 9 strains, respectively. Interestingly, a MVA/ Y. pestis recombinant that expressed the capsular protein (F1) did not elicit significant antibody titers but still conferred 50% and 25% protection against CO92 or Java 9 challenge, respectively. The MVA/ Y. pestis recombinant viruses did not demonstrate any mortality or morbidity in SCID mice. Based on their safety and efficacy in mice, these MVA/ Y. pestis recombinants are candidates for further development as biodefense and public health vaccines.