Revaccination of Guinea Pigs With the Live Attenuated Mycobacterium tuberculosis Vaccine MTBVAC Improves BCG's Protection Against Tuberculosis.
The need for an effective vaccine against human tuberculosis has driven the development of different candidates and vaccination strategies. Novel live attenuated vaccines are being developed that promise greater safety and efficacy than BCG against tuberculosis. We combined BCG with the vaccine MTBVAC to evaluate whether the efficacy of either vaccine would be affected upon revaccination.



In a well-established guinea pig model of aerosol infection with Mycobacterium tuberculosis, BCG and MTBVAC delivered via various prime-boost combinations or alone were compared. Efficacy was determined by a reduction in bacterial load 4 weeks after challenge.



Efficacy data suggests MTBVAC-associated immunity is longer lasting than that of BCG when given as a single dose. Long and short intervals between BCG prime and MTBVAC boost resulted in improved efficacy in lungs, compared with BCG given alone. A shorter interval between MTBVAC prime and BCG boost resulted in improved efficacy in lungs, compared with BCG given alone. A longer interval resulted in protection equivalent to that of BCG given alone.



These data indicate that, rather than boosting the waning efficacy of BCG, a vaccination schedule involving a combination of the 2 vaccines yielded stronger immunity to M. tuberculosis infection. This work supports development of MTBVAC use as a revaccination strategy to improve on the effects of BCG in vaccinated people living in tuberculosis-endemic countries.
Public Health England, Salisbury,United Kingdom.
Simon
S
Clark
Public Health England, Salisbury,United Kingdom.
Faye
F
Lanni
Department of Microbiology, Faculty of Medicine, University of Zaragoza.
Dessislava
D
Marinova
Public Health England, Salisbury,United Kingdom.
Emma
E
Rayner
Department of Microbiology, Faculty of Medicine, University of Zaragoza.|Servicio de Microbiología, Hospital Miguel Servet, ISS Aragón, Zaragoza.|Biomedical Research Center for Respiratory Diseases, Research Network on Respiratory Diseases, Spanish Ministry of Health, Instituto de Salud Carlos III, Madrid, Spain.
Carlos
C
Martin
Public Health England, Salisbury,United Kingdom.
Ann
A
Williams
D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000276:immunology; D004195:Disease Models, Animal; D006168:Guinea Pigs; D007117:Immunization, Secondary; D008168:Lung / Q000276:immunology / Q000382:microbiology; D009169:Mycobacterium tuberculosis; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage* / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
D001500:BCG Vaccine; D032581:Tuberculosis Vaccines; D014613:Vaccines, Attenuated
MTBVAC; Tuberculosis; aerosol; guinea pig; vaccine