Thanks to funding from the Pershing Square Foundation, the Bluebell Foundation and the U.S. Center for Disease Control and Prevention (CDC), researchers at the Bandim Health Project are now able to initiate a randomized controlled trial of the hepatitis B vaccine at birth in Guinea-Bissau. There is a unique window of opportunity, because the Guinean Ministry of Health has decided to implement a universal hepatitis B vaccine policy for newborns starting in 2027/28. Until then, the team will randomize newborns to receive a WHO-approved hepatitis B vaccine at birth (the future policy) or no hepatitis B vaccine at birth (the current policy). All children will receive the currently recommended BCG and OPV vaccines, irrespective of allocation.
The trial will enroll participants until hepatitis B vaccine is to be implemented in the National vaccination program in Guinea-Bissau. By that time, enrollment will end and Bandim Health Project will assist with the implementation of the new policy, and continue follow-up of the cohort for a total of 5 years. The primary outcome is overall mortality and hospitalizations, secondary outcomes are atopic dermatitis and neurodevelopment.
The trial team is grateful to the donors for supporting this evaluation of a widely used vaccine, which will be the first and likely the only one of its kind. The trial was approved by the Guinean National Ethics Committee in November 2025, and received final funding in December 2025. Preparations are ongoing.
Scientific Background
The trial builds on Bandim Health Project’s more than 40 years of research into the overall health effects of vaccines. This research has led to the insight that vaccines, in addition to their well-known disease-specific effects, also have broader effects on the immune system and its ability to handle other infections. For example, providing the BCG vaccine against tuberculosis at birth can protect children from dying from severe infections that carry a high mortality in low-income settings. The hepatitis B vaccine at birth has never been tested on a large scale for its overall health effects, so it is unknown whether the vaccine has non-specific health effects. Researchers at the Bandim Health Project have thus long had a wish to evaluate whether the hepatitis B vaccine at birth may also have such non-specific effects. Two observational studies from The Gambia and Guinea-Bissau have raised questions about possible sex-differential overall mortality effects following hepatitis B vaccination. The upcoming national introduction of hepatitis B vaccination at birth in Guinea-Bissau creates a unique and time-limited policy window to conduct such a trial ethically: the study compares current practice with a policy that has already been decided but not yet implemented.
Funding and Independence
The study was designed by researchers at the Bandim Health Project and builds directly on their longstanding research program. Funding was sought from multiple international foundations, and support was provided by the Pershing Square Foundation, the Bluebell Foundation, and lastly the U.S. CDC. The funders did not commission the trial, nor do they have any influence on its design or conduct.
Addressing Common Misunderstandings
Several misconceptions about the trial have circulated on social media. The researchers would like to clarify the following points:
- No vaccines are being withheld. No newborn in Guinea-Bissau will receive fewer vaccines because of this study. All participants receive BCG and OPV, which are the standard vaccines given at birth. All children are provided hepatitis B vaccine at 6, 10 and 14 weeks of age as a part of the current vaccination program. Half of the participants receive an additional hepatitis B vaccine dose at birth that they would not otherwise have received.
- Vaccination coverage will increase. Trial vaccination teams will operate every day of the year, including weekends and holidays. This is expected to increase timely vaccination coverage compared with routine services.
- The study does not set out to test whether hepatitis B vaccination prevents hepatitis B. That effect is already well established. The trial’s focus is on the overall health outcomes, including potential non-specific effects, which have never been evaluated in a randomized design at this scale.
- The hepatitis B vaccine is not new. The trial examines an existing, WHO prequalified hepatitis B vaccine, which is universally recommended.
Why This Trial Matters
The hepatitis B vaccine at birth has recently been the subject of public debate. While opinions differ, robust evidence from randomized trials is currently lacking. This study will provide high-quality data to inform future discussions and policy decisions, moving the debate beyond speculation and observational findings.
The results will be most directly relevant to Guinea-Bissau and similar low-income settings. However, they will contribute to the global scientific understanding of how vaccination affects overall child health.
The research team is grateful to the funding partners for making possible what is likely to be the first – and potentially only – randomized trial of the overall health effects of hepatitis B vaccination at birth.
Contacts:
Principal investigator: Frederik Schaltz-Buchholzer, MD, PhD, fschaltz-buchholzer@health.sdu.dk.
Isaquel da Silva, MD, PhD Fellow, idasilva@health.sdu.dk.