Neonatal revaccination with Bacillus Calmette–Guérin elicits improved, early protection against Mycobacterium tuberculosis in mice

Abstract

The protective effect of revaccination with Mycobacterium bovis Bacillus Calmette–Guérin (BCG) against Mycobacterium tuberculosis in animals is controversial. To investigate whether revaccination of neonates with BCG could improve the protection against M. tuberculosis, C57BL/6 neonates were vaccinated with BCG on day 1, or on days 1, 7, and 14, and the mice at eight weeks of age were challenged with M. tuberculosis and monitored for survival. The M. tuberculosis burden in their livers and lungs, the pathological changes in the lungs, their splenic T cell responses and serum cytokines were examined longitudinally post-challenge. BCG vaccination significantly prevented the M. tuberculosis-related mouse death and reduced the burden of M. tuberculosis in the liver and lungs, and lung damage in the mice, particularly at early stage of the pathogenic process in the BCG-revaccinated mice. However, the BCG revaccination-induced protection waned over time. BCG vaccination did not significantly modulate the levels of serum IFN-γ and the frequency of splenic PPD-reactive IFN-γ-secreting T cells, but significantly decreased the levels of serum TNF-α and PPD-specific IL-4 responses at 3 weeks post challenge. Taken together, these data suggest that revaccination of neonates with BCG elicits improved, early protection against M. tuberculosis by modulating cytokine responses in adult mice.