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A paradox of TB immunity
  1. K Dheda
  1. Specialist Registrar, Royal Free Hospital and Centre for Infectious Diseases and International Health, University College London and Royal Free Medical School, London, UK;

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To address whether protective immunity induced by natural infection was any different from that induced by BCG, investigators infected mice—either BCG vaccinated or previously infected with M tuberculosis and then cured with chemotherapy—with a low dose of M tuberculosis H37Rv. Protection against post primary M tuberculosis infection did not differ significantly between the two groups even when adoptive transfer of interferon (IFN)-γ positive splenocytes or serum was performed. After challenge infection, the number of IFN-γ positive splenocytes did not differ significantly between the groups. The authors conclude that, in this murine model, natural infection with M tuberculosis and vaccination with BCG do not differ in their capacity to induce protective immunity against tuberculosis. Consequently, any novel vaccine against tuberculosis has to perform better than both vaccination with BCG and immunity evoked by natural infection.

This study highlights one of the great paradoxes of tuberculosis: natural infection does not confer protective immunity yet only 10% of those that are infected progress to active disease. Indeed, recent human molecular epidemiological studies show that previous infection does not protect against re-infection progressing to active disease and, moreover, at the site of human disease there are high IFN-γ levels. This study raises the question of whether the strategy to identify vaccine candidates by using the IFN-γ response as a surrogate marker of protective immunity is a valid one. The future challenge will be to identify other correlates of protective immunity or, alternatively, components of M tuberculosis that induce a subversive host response.

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