Prevention of tuberculosis in macaques after intravenous BCG immunization

Changing the dose and delivery route of the BCG vaccine improves protection against tuberculosis infection in a rhesus macaque model of the disease reports a study published in Nature this week. The data suggest that switching the delivery mode from intradermal to intravenous could be especially beneficial when given to adolescents or adult humans, although clinical tests are needed.

The only licensed tuberculosis vaccine is BCG, which is given intradermally, but is less effective against pulmonary infection in adolescents and adults. However, intradermal administration does not induce the high frequencies of specific T cells in the lung likely needed to mediate high level protection against infection and disease. Robert Seder and colleagues hypothesized that delivering higher doses of the BCG vaccine intravenously may boost levels of protective T cells in the lung, and they test this theory in rhesus macaques, which are highly susceptible to tuberculosis. They show that nine out of ten animals that received intravenous BCG doses, which were 100 times higher than the standard dose in humans, were highly protected, with six showing no detectable signs of infection after exposure to Mycobacterium tuberculosis. By contrast, only two out of ten macaques that received these higher doses of BCG either intradermally or by aerosol immunization showed no signs of infection after being exposed to M. tuberculosis.

The authors propose that their findings support the clinical development of intravenous delivery of BCG in adolescents or adults, which could have the greatest effect on reducing tuberculosis transmission. They also suggest that the intravenous route may also improve the protective capacity of other vaccines designed to elicit T cells at tissue sites.

doi:10.1038/s41586-019-1817-8

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