Research ArticleTuberculosis

A Human Type 5 Adenovirus–Based Tuberculosis Vaccine Induces Robust T Cell Responses in Humans Despite Preexisting Anti-Adenovirus Immunity

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Science Translational Medicine  02 Oct 2013:
Vol. 5, Issue 205, pp. 205ra134
DOI: 10.1126/scitranslmed.3006843

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Boosting BCG

Bacille Calmette-Guérin (BCG) has long been the standard vaccine for tuberculosis (TB). However, with TB incidence on the rise, especially in communities with heavy HIV prevalence, new vaccines are needed to work with BCG to accentuate the immune response. One such way to boost a primed immune response is by delivering pathogen-specific target antigens using adenoviral vectors. Yet, which adenovirus to use remains a matter of debate: People frequently have preexisting neutralizing antibodies to the more immunogenic vectors, and rarer vectors tend to be less immunogenic. Now, Smaill et al. show that a recombinant human type 5 adenovirus (AdHu5) has safety and efficacy in both BCG and BCG+ adults with little observed effect of preexisting neutralizing antibodies.

The authors immunized healthy subjects intramuscularly with their AdHu5 vector. The immunization was safe, well tolerated, and immunogenic in both BCG and BCG+ individuals. However, individuals previously vaccinated with BCG were more likely to have polyfunctional T cell responses, which have been associated with protection. What’s more, although the patient numbers are small, Smaill et al. did not see an appreciable effect of preexisting neutralizing antibodies on the vaccine’s ability to boost the immune response. These data suggest that, at least for certain antigens, adenovirally delivered boosts can enhance the immune response to TB.