Inclusion of young adolescents in policy development for new tuberculosis vaccines

The infant tuberculosis vaccine, BCG, prevents severe tuberculosis disease, but protection is rarely durable beyond childhood. New tuberculosis vaccines are being developed for the prevention of infectious pulmonary tuberculosis in older adolescents and adults, but younger adolescents have been historically excluded from clinical trials of new tuberculosis vaccines. Reasons to include young adolescents (aged 9-14 years) in tuberculosis vaccine policy development include the opportunity to vaccinate before the age-related increase in risk of tuberculosis disease, as well as increased rates of HIV acquisition and pregnancy, which are both independently associated with tuberculosis risk, and the opportunity to implement tuberculosis vaccination with delivery of other school-age vaccines, such as human papillomavirus. These advantages are offset by several challenges, including testing vaccine efficacy in an age group with low rates of tuberculosis case accrual; low rates of Mycobacterium tuberculosis sensitisation, which might compromise bridging of immune correlates of protection from adults; and modest modelled population impact of vaccination of young adolescents, compared with mass campaigns in older age groups with higher tuberculosis incidence. Notably, if a tuberculosis vaccine that was effective only in individuals who are infected with M tuberculosis was rolled out exclusively to young adolescents, the projected low population impact could take many years to detect. We propose that challenges to the inclusion of young adolescents should be considered explicitly in the development of tuberculosis vaccine policy, so that they do not risk exclusion from the direct benefits of vaccination. We describe an alternative efficacy trial design, which would leverage higher rates of tuberculosis case accrual after recent household tuberculosis exposure, to deliver both vaccine efficacy data and validation of an immune correlate of protection. This novel strategy, together with licensure data from older populations, might support rapid implementation of new, effective tuberculosis vaccines for young adolescents.