The Centers for Disease Control and Prevention (CDC) has awarded an unsolicited, single-source grant to the University of Southern Denmark (SDU) to support a large randomized clinical trial evaluating the health effects of neonatal monovalent hepatitis B vaccination in Guinea-Bissau, according to a notice scheduled for publication in the Federal Register on December 18, 2025.¹
The award provides approximately $1.6 million over five years, covering the period from January 5, 2026, through January 4, 2031, and will fund a single-blind, multicenter, phase 4 randomized controlled trial enrolling more than 14,000 newborns. The study will assess the effects of hepatitis B virus (HBV) vaccine administered at birth on all-cause mortality, severe morbidity, and long-term neurodevelopmental outcomes, as well as evaluate potential sex-specific differences in vaccine effects.¹
The trial will be conducted in Guinea-Bissau, a low-income setting where the World Health Organization recommends administration of 3 vaccines at birth, Bacille Calmette-Guérin (BCG), oral polio vaccine (OPV0), and hepatitis B vaccine. While BCG and OPV have been studied for broader effects on child health, the CDC noted that evidence regarding non–hepatitis-specific health effects of HBV remains limited, prompting further randomized evaluation of early-life outcomes.¹
CDC determined that SDU was uniquely qualified to conduct the research based on its experience leading vaccine trials in West Africa, established partnerships with local hospitals and health authorities in Guinea-Bissau, and prior work in neonatal and pediatric research in low-resource settings. The grant was awarded non-competitively, as there was no current or planned funding opportunity under which the proposal could compete.¹ According to the CDC, findings from the study are expected to inform global immunization policy and practice, particularly regarding the broader health effects of neonatal hepatitis B vaccination beyond prevention of hepatitis B virus infection.¹
The study enters an ongoing scientific debate over non-specific effects (NSEs) of vaccines, defined as health effects beyond protection against their target pathogens. Much of the randomized trial evidence cited in support of NSEs has originated from studies conducted by the Bandim Health Project, led by Christine Stabell Benn and Peter Aaby. According to a November 2025 analysis published in Vaccine, researchers affiliated with the Bandim Health Project accounted for approximately 35% of all clinical research articles on NSEs indexed in Web of Science, excluding reviews.²
What You Need to Know
The CDC awarded a five-year, single-source grant to the University of Southern Denmark to conduct a randomized trial of neonatal hepatitis B vaccination in Guinea-Bissau involving more than 14,000 newborns.
The study will assess all-cause mortality, severe morbidity, long-term developmental outcomes, and potential sex-specific effects of the hepatitis B birth dose.
The trial enters an active scientific debate over non-specific vaccine effects, with prior randomized evidence and methodology remaining contested.
In the analysis, Henrik Støvring, PhD, and colleagues reassessed randomized controlled trials conducted by the Bandim Health Project following Danish media reports that raised concerns about research practices. The authors reviewed 40 published papers reporting randomized trials and included 26 trials registered at ClinicalTrials.gov in their reanalysis.²
The review found that in 23 of 25 randomized trial papers, Bandim Health researchers emphasized secondary findings, and that in 22 cases those findings were no longer statistically significant after appropriate statistical adjustments. The authors reported multiple methodological concerns, including unpublished primary outcomes, outcome switching, reliance on statistically fragile subgroup analyses, selective emphasis on secondary findings when primary outcomes were null, and underpowered sample-size calculations based on optimistic assumptions. To address the risk of false-positive findings due to multiple hypothesis testing, the authors applied Holm–Bonferroni and Benjamini–Hochberg procedures, after which many previously reported statistically significant results did not remain so.²
The authors cautioned that randomized trials can inform policy only to the extent that analysis and reporting practices are reliable, and that secondary or exploratory findings should be interpreted carefully when primary outcomes fail to reach statistical significance.²
Several experts also questioned the ethical and scientific rationale for conducting another hepatitis B vaccine study, citing extensive existing evidence supporting the vaccine’s safety and effectiveness. One being, Angela Rasmussen, PhD, who said awarding a noncompetitive grant for the research gives the “appearance of blatant cronyism,” while Amesh A Adalja, MD, said safety data for hepatitis B vaccines are “very robust” and that additional studies may represent a misallocation of limited research funding.³
As the trial proceeds, its results are expected to contribute additional randomized evidence to ongoing discussions about neonatal hepatitis B vaccination, particularly regarding outcomes beyond prevention of hepatitis B virus infection. How these findings are interpreted alongside the existing body of vaccine safety and effectiveness data may have implications for global immunization policy.
References
1.CDC. Notice of Award of a Single Source Unsolicited Grant to Fund University of Southern Denmark (SDU). December 18, 2025. Accessed December 19, 2025. https://public-inspection.federalregister.gov/2025-23245.pdf
2.Støvring H, Ekstrøm C, Schneider J, Strøm C. What is actually the emerging evidence about non-specific vaccine effects in randomized trials from the Bandim Health Project? ScienceDirect. November 27, 2025. Accessed December 19, 2025. https://doi.org/10.1016/j.vaccine.2025.127937
