An experimental tuberculosis vaccine designed to improve on the century-old BCG shot did not prove as good as BCG at preventing tuberculosis infection in newborns, according to one of the largest infant tuberculosis vaccine trials ever run.
The phase 3 priMe trial tested VPM1002, a genetically modified version of BCG, against the standard vaccine at ten main sites and four satellite sites across sub-Saharan Africa. Results were published in The Lancet Infectious Diseases and covered in the infectious disease trade press.
Investigators enrolled 6,950 infants. After ten withdrawals, 6,940 were randomly assigned, and 6,897 were vaccinated. Healthy newborns aged 0 to 14 days weighing at least 2.3 kilograms received a single intradermal dose of either VPM1002 or BCG. The group included 720 infants born to mothers living with HIV.
No American infant receives BCG routinely, so nothing here changes any U.S. vaccination schedule. The relevance is narrower and worth stating plainly: tuberculosis remains among the world's deadliest infectious diseases, the only licensed vaccine was first given to a human in 1921, and this was one of the better-resourced attempts to replace it.
The Result and the Margin It Missed
The primary endpoint was not tuberculosis disease. It was infection, measured by conversion on the QuantiFERON-TB Gold Plus blood test, an interferon-gamma release assay.
Over a median follow-up of 35 months, conversion occurred in 184 of 3,471 infants in the VPM1002 group (5.3%), compared with 150 of 3,469 infants in the BCG group (4.3%). The hazard ratio was 1.23, with a 95% confidence interval ranging from 0.99 to 1.53.
Noninferiority required the upper bound of that interval to fall below 1.25. It reached 1.53. The trial therefore did not show that VPM1002 is at least as good as BCG on this measure.
Safety was not the problem. Adverse event profiles, including serious events and deaths, were similar between the two groups, and no vaccine-related serious adverse events were reported in either arm.
Several Problems Complicate the Reading
The investigators flagged limitations that make this a murkier result than a simple failure, and readers should weigh them before drawing conclusions.
The trial never achieved the statistical power it was designed to have. Only 334 of the planned 632 infection events occurred, even after follow-up was extended from 36 months to 48 months. The trial was stopped early in October 2024 because the conversion rate remained below expectations. A study that falls roughly half short of its planned events cannot deliver a confident verdict in either direction, which is why the lower bound of the confidence interval sits at 0.99, just touching no difference.
The groups were also not evenly exposed. Household tuberculosis exposure ran about 33 percent higher in the VPM1002 group. When investigators added exposure as a covariate, the model's proportional hazards assumption was violated, meaning the effect of exposure on conversion changed over time, and the hazard ratio could not be reliably estimated without more complex modeling.
Then there is the endpoint itself. The authors reported discordance between QuantiFERON conversion and confirmed tuberculosis disease, and concluded that their findings expose a broader problem with using infection defined by interferon-gamma release assays as a stand-in for disease in infant vaccine trials. That is a methodological finding with implications well beyond this one candidate.
The first author was Videlis Nduba of the Kenya Medical Research Institute and its Center for Respiratory Disease Research. Funding came through the European and Developing Countries Clinical Trials Partnership 2 program, supported by the European Union and co-funded by the German Aerospace Center and the European Investment Bank. VPM1002 grew out of work by researchers including Stefan Kaufmann of the Max Planck Institute for Infection Biology, and was developed for licensure by the Serum Institute of India and its European affiliate. An earlier phase 2 trial in South African newborns found the candidate to be less reactogenic than BCG, although immune responses were higher with BCG.
Relevance Beyond the Trial Countries
Tuberculosis is not a historical disease. It sickens more than 10 million people worldwide each year and kills more than a million. In the United States, the CDC's provisional surveillance report counted 10,260 cases in 2025, a rate of 3.0 per 100,000 and a 1 percent decline from the prior year. About 77 percent of U.S. cases occur among people born outside the country.
BCG is not part of the routine U.S. immunization schedule because domestic rates are low and the vaccine interferes with tuberculin skin testing. It is given in most high-burden countries, where it reliably reduces severe childhood forms of the disease, such as tuberculous meningitis, but offers variable, often poor protection against pulmonary tuberculosis in adolescents and adults, and limited protection against infection and transmission.
That gap is why a replacement has been sought for decades. Closing it would matter to American households mainly through travel, immigration and global disease control rather than through any change at a pediatrician's office.
The Pipeline After This Result
The priMe trial is complete. What it leaves behind is a candidate without a demonstrated advantage, and a live question about how future infant trials should be designed.
Other next-generation candidates remain in development, and the World Health Organization has said new vaccines are needed to meet global tuberculosis reduction targets. Whether regulators, funders or the manufacturer pursue VPM1002 further has not been announced.
For readers, no action follows from this result. Anyone traveling to or from a country with high tuberculosis rates, anyone with a known exposure, and anyone with a cough lasting more than two to three weeks, unexplained weight loss, night sweats or fever should raise it with a clinician, who can arrange testing. The CDC's tuberculosis surveillance program frames elimination as a dual task of treating active disease and treating latent infection before it progresses. Latent infection is treatable, and treatment substantially reduces the chance of progressing to active disease.
MedicalDaily will report further peer-reviewed analyses of the priMe data, any regulatory or sponsor decisions on VPM1002, and results from other late-stage tuberculosis vaccine candidates as they are released.
Key Questions Answered
What is VPM1002? A recombinant version of the BCG vaccine, genetically modified with the aim of producing better protection against tuberculosis than the original.
What did the trial find? VPM1002 did not show noninferiority to BCG for preventing tuberculosis infection in newborns. The hazard ratio was 1.23 with an upper confidence bound of 1.53, above the prespecified margin of 1.25.
Does that mean the vaccine is unsafe? No. Adverse events, serious adverse events, and deaths were similar between groups, and no vaccine-related serious adverse events were reported in either arm.
Why is the result hard to interpret? The trial accrued only 334 of a planned 632 infection events and stopped early; household tuberculosis exposure was about 33 percent higher in the VPM1002 group, and the blood-test endpoint did not align well with confirmed disease.
Does this affect vaccines given to U.S. children? No. BCG is not part of the routine U.S. immunization schedule, and this trial involved no vaccine used in routine American pediatric care.
Is BCG still recommended elsewhere? Yes. BCG remains the only tuberculosis vaccine in widespread use and continues to reduce severe childhood forms of the disease.
What should someone do if they are concerned about tuberculosis exposure? Contact a clinician about testing. Latent infection can be identified and treated, progressing to active disease.
