Vaccines protect people against infectious diseases, but several important vaccines do not work as well in low income countries (LICs) compared to high-income countries (HICs) and in rural, compared to urban, settings. One possible reason for this might be that people living in these settings are more likely to have worm infections. Worm infections impact on the immune system and may change an infected person’s response to a vaccine. This study aims to investigate whether treating adolescents infected with schistosomiasis, a parasitic worm infection, before vaccination, will lead to a better immune response to these vaccines.
A second possible reason for differences in vaccine response is exposure to malaria. Malaria infections impact on the immune system and may change an infected person’s response to a vaccine. This study aims to investigate whether giving adolescents presumptive treatment for malaria, before vaccination, will lead to a better immune response to these vaccines.
BCG is the only licensed vaccine for prevention of tuberculosis. It is given at birth in countries where tuberculosis is common and works well at preventing tuberculosis in childhood, but less well at preventing tuberculosis later in life. However, it is thought that BCG may have other effects unrelated to tuberculosis (so called “non-specific” effects and benefits). One of these is that BCG might improve how someone responds to other unrelated vaccinations. This study aims to investigate whether giving BCG beforehand will improve the immune response to unrelated vaccines.
POPVAC’s goal is to understand population differences in vaccine response in order to identify strategies through which vaccine effectiveness can be optimized for tropical settings like Uganda. It will achieve this by carrying out a set of 3 clinical trials (Trial A, B and C) over a period of 4 years. This four–year project began in 2018.
Trials A and B will involve two rural adolescent cohorts recruited from primary schools in Koome Islands in Mukono district, and from Jinja district, targeting settings with high prevalence of schistosomiasis and malaria respectively. Trial C will involve an urban cohort recruited from Entebbe in Wakiso district. It is funded by the Medical Research Council UK.
We hypothesise that urban-rural (and by extension regional and international) differences in vaccine responses are mediated to an important extent by differential exposure to chronic infections, particularly parasitic infections; that parasites act in part via “trans-kingdom” effects including herpesvirus activation, and immune modulation resulting from translocation of microbial products from the gut into the systemic circulation; and that these exposures impact the pre-immunisation immune profile and hence vaccine response.
This research programme, whose Principal Investigator is Professor Alison Elliott, is based at the Medical Research Council (MRC)/Uganda Virus Research Institute (UVRI) & London School of Hygiene and Tropical Medicine (LSHTM) Uganda Research Unit in Entebbe.
Clinical Senior Scientist
Assistant Professor in Immunology
Director, MRC/UVRI and LSHTM Uganda Research Unit
Linda Rosset Buluma
Christine Nankabirwa Musoke
POPVAC’s research portfolio consists of three clinical trials.
POPVAC A comprises a trial designed to determine the effect of intensive treatment for schistosomiasis on response to vaccines among island adolescents.
This is an interventional study comparing intensive versus standard praziquantel intervention for S. mansoni infection on vaccine response outcomes. Adolescents aged 9 to 17 years from primary 4 to 6 school children in the Koome islands where schistosomiasis is highly endemic (approximately 80% are infected in this age group) were recruited. We enrolled about 480 children into the trial, 240 in each trial arm. Participants in the intensive arm received three doses of praziquantel (PZQ) (40mg/kg, assessed by height pole) each two weeks apart (the last of these 2-4 weeks before immunisation), followed by quarterly during follow up. Participants in the standard arm received annual PZQ (Uganda Ministry of Health (MoH) policy).
All participants received a standardised portfolio of licensed 5 vaccines: BCG, Yellow Fever, oral typhoid (Ty21a), HPV, and tetanus/diphtheria on three main immunisation days (week 0, week 4 and week 28). Blood, urine and Stool samples are being used for diagnostic and immunological tests.
Outcome analysis is in progress. Outcomes will be laboratory based assessments of immune responses to the five vaccines.
POPVAC B comprises a trial designed to determine the effect of Intermittent preventive treatment for malaria on response to vaccines among rural adolescents.
This is a double-blinded interventional study comparing the effect of monthly preventive treatment of malaria with dihydroartemisinin-piperaquine (DP) versus placebo on vaccine response outcomes.
Adolescents aged 9 to 17 years from primary 4 to 6 school children in Jinja district, selecting sub-counties away from Lake Victoria and the River Nile where malaria is highly endemic but schistosomiasis is uncommon will be recruited. We plan to enrol 640 children into the trial, 320 in each trial arm. One arm will receive the DP treatment and the other a DP placebo.
Participants will receive the same standardised portfolio of licensed vaccines as participants in POPVAC A, and the outcomes will also be the same.
POPVAC C comprises an observational study on life-course exposures that impact vaccine responses in adolescents, to be undertaken among participants in the Entebbe Mother and Baby Study birth cohort, and a nested trial designed to determine the effect of BCG re-vaccination on the response to unrelated vaccines.
The nested trial will be an interventional study investigating the effect of BCG revaccination on unrelated vaccine response outcomes. Adolescents who were enrolled prenatally into the Entebbe Mother and Baby Study birth cohort will be recruited.
We plan to enrol up to 300 EMaBS participants in this study, 150 participants in both the BCG revaccination arm and in the non – BCG revaccination arm.
All participants will otherwise receive the same standardised portfolio of licensed vaccines as participants in POPVAC A, and the outcomes will also be the same.