A Replication-Defective Human Type 5 Adenovirus-Based Trivalent Vaccine Confers Complete Protection against Plague in Mice and Nonhuman Primates

Jian Sha; Michelle L Kirtley; Curtis Klages; Tatiana E Erova; Maxim Telepnev; Duraisamy Ponnusamy; Eric C Fitts; Wallace B Baze; Satheesh K Sivasubramani; William S Lawrence; Igor Patrikeev; Jennifer E Peel; Jourdan A Andersson; Elena V Kozlova; Bethany L Tiner; Johnny W Peterson; David McWilliams; Snehal Patel; Eric Rothe; Vladimir L Motin; Ashok K Chopra

doi:10.1128/CVI.00150-16

A Replication-Defective Human Type 5 Adenovirus-Based Trivalent Vaccine Confers Complete Protection against Plague in Mice and Nonhuman Primates

Clin Vaccine Immunol. 2016 Jul 5;23(7):586-600. doi: 10.1128/CVI.00150-16. Print 2016 Jul.

Authors

Jian Sha¹, Michelle L Kirtley², Curtis Klages³, Tatiana E Erova², Maxim Telepnev⁴, Duraisamy Ponnusamy², Eric C Fitts², Wallace B Baze⁵, Satheesh K Sivasubramani⁶, William S Lawrence⁷, Igor Patrikeev⁸, Jennifer E Peel⁷, Jourdan A Andersson², Elena V Kozlova², Bethany L Tiner², Johnny W Peterson⁹, David McWilliams¹⁰, Snehal Patel¹⁰, Eric Rothe¹⁰, Vladimir L Motin¹¹, Ashok K Chopra¹²

Affiliations

¹ Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, USA jisha@utmb.edu achopra@utmb.edu.
² Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
³ Animal Resource Center, University of Texas Medical Branch, Galveston, Texas, USA.
⁴ Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
⁵ Department of Veterinary Sciences, M.D. Anderson Cancer Center, Bastrop, Texas, USA.
⁶ Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA.
⁷ Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA.
⁸ Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, Texas, USA.
⁹ Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, USA Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA WHO Collaborating Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, USA.
¹⁰ Norwell, Inc., Houston, Texas, USA.
¹¹ Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, USA Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA WHO Collaborating Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, USA.
¹² Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, USA Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA WHO Collaborating Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, USA jisha@utmb.edu achopra@utmb.edu.

Abstract

Currently, no plague vaccine exists in the United States for human use. The capsular antigen (Caf1 or F1) and two type 3 secretion system (T3SS) components, the low-calcium-response V antigen (LcrV) and the needle protein YscF, represent protective antigens of Yersinia pestis We used a replication-defective human type 5 adenovirus (Ad5) vector and constructed recombinant monovalent and trivalent vaccines (rAd5-LcrV and rAd5-YFV) that expressed either the codon-optimized lcrV or the fusion gene designated YFV (consisting of ycsF, caf1, and lcrV). Immunization of mice with the trivalent rAd5-YFV vaccine by either the intramuscular (i.m.) or the intranasal (i.n.) route provided protection superior to that with the monovalent rAd5-LcrV vaccine against bubonic and pneumonic plague when animals were challenged with Y. pestis CO92. Preexisting adenoviral immunity did not diminish the protective response, and the protection was always higher when mice were administered one i.n. dose of the trivalent vaccine (priming) followed by a single i.m. booster dose of the purified YFV antigen. Immunization of cynomolgus macaques with the trivalent rAd5-YFV vaccine by the prime-boost strategy provided 100% protection against a stringent aerosol challenge dose of CO92 to animals that had preexisting adenoviral immunity. The vaccinated and challenged macaques had no signs of disease, and the invading pathogen rapidly cleared with no histopathological lesions. This is the first report showing the efficacy of an adenovirus-vectored trivalent vaccine against pneumonic plague in mouse and nonhuman primate (NHP) models.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adenoviruses, Human / genetics*
Administration, Intranasal
Animals
Antibodies, Bacterial / blood
Antigens, Bacterial / genetics
Antigens, Bacterial / immunology
Disease Models, Animal
Drug Carriers*
Female
Immunization Schedule
Injections, Intramuscular
Interferon-gamma / metabolism
Macaca fascicularis
Male
Mice
Plague / pathology
Plague / prevention & control*
Plague Vaccine / administration & dosage
Plague Vaccine / genetics
Plague Vaccine / immunology*
Survival Analysis
T-Lymphocytes / immunology
Vaccines, Synthetic / administration & dosage
Vaccines, Synthetic / genetics
Vaccines, Synthetic / immunology
Virus Replication
Yersinia pestis / genetics
Yersinia pestis / immunology

Substances

Antibodies, Bacterial
Antigens, Bacterial
Drug Carriers
Plague Vaccine
Vaccines, Synthetic
Interferon-gamma

Abstract

Publication types

MeSH terms

Substances

Grants and funding