Abstract
Introduction
Vaccine-specific immune responses vary between populations and are
often impaired in low income, rural settings. Drivers of these
differences are not fully elucidated, hampering identification of
strategies for optimising vaccine effectiveness. We hypothesise that
urban–rural (and regional and international) differences in vaccine
responses are mediated to an important extent by differential exposure
to chronic infections, particularly parasitic infections.
Methods and analysis
Three related trials sharing core elements of study design and
procedures (allowing comparison of outcomes across the trials) will test
the effects of (1) individually randomised intervention against
schistosomiasis (trial A) and malaria (trial B), and (2) Bacillus
Calmette-Guérin (BCG) revaccination (trial C), on a common set of
vaccine responses. We will enrol adolescents from Ugandan schools in
rural high-schistosomiasis (trial A) and rural high-malaria (trial B)
settings and from an established urban birth cohort (trial C). All
participants will receive BCG on day ‘0’; yellow fever, oral typhoid and
human papilloma virus (HPV) vaccines at week 4; and HPV and
tetanus/diphtheria booster vaccine at week 28. Primary outcomes are
BCG-specific IFN-γ responses (8 weeks after BCG) and for other vaccines,
antibody responses to key vaccine antigens at 4 weeks after
immunisation. Secondary analyses will determine effects of interventions
on correlates of protective immunity, vaccine response waning, priming
versus boosting immunisations, and parasite infection status and
intensity. Overarching analyses will compare outcomes between the three
trial settings. Sample archives will offer opportunities for exploratory
evaluation of the role of immunological and ‘trans-kingdom’ mediators in
parasite modulation of vaccine-specific responses.
Ethics and dissemination
Ethics approval has been obtained from relevant Ugandan and UK
ethics committees. Results will be shared with Uganda Ministry of
Health, relevant district councils, community leaders and study
participants. Further dissemination will be done through conference
proceedings and publications.
Trial registration numbers
NCT60517191,NCT62041885,NCT10482904.