ABSTRACT
Priming neonatal calves at birth with a Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine and boosting with a DNA vaccine consisting of plasmids encoding mycobacterial antigens Hsp65, Hsp70, and Apa or the reverse prime-boost sequence induced similar levels of protection against experimental challenge with Mycobacterium bovis. When M. bovis was isolated from a thoracic lymph node following challenge, the two groups of calves given the prime-boost regimen had significantly lower numbers of M. bovis isolates than those vaccinated with BCG alone. These observations suggest that the exact sequence of administration of a prime-boost vaccination regimen in a neonatal animal model is not critical to the development of immunity.
Subject(s)
BCG Vaccine/immunology , Bacterial Proteins/immunology , Chaperonins/immunology , HSP70 Heat-Shock Proteins/immunology , Tuberculosis, Bovine/prevention & control , Vaccines, DNA/immunology , Animals , Animals, Newborn , Bacterial Proteins/genetics , Cattle , Chaperonin 60 , Chaperonins/genetics , HSP70 Heat-Shock Proteins/genetics , Interferon-gamma/biosynthesis , Interleukin-2/biosynthesis , VaccinationABSTRACT
Tuberculosis is responsible for >2 million deaths a year, and the number of new cases is rising worldwide. DNA vaccination combined with Mycobacterium bovis bacillus Calmette Guerin (BCG) represents a potential strategy for prevention of this disease. Here, we used a heterologous prime-boost immunization approach using a combination of DNA plasmids and BCG in order to improve the efficacy of vaccination against Mycobacterium tuberculosis infection in mice. As model antigens, we selected the M. tuberculosis Apa (for alanine-proline-rich antigen) and the immunodominant Hsp65 and Hsp70 mycobacterial antigens combined with BCG. We demonstrated that animals injected with a combination of DNA vectors expressing these antigens, when boosted with BCG, showed increased specific antimycobacterial immune responses compared to animals vaccinated with BCG alone. More importantly, the protection achieved with this regimen was also significantly better than with BCG alone.
