The Oxford-led study demonstrated that an oral live-attenuated vaccine, CVD 1902, provided significant protection against S. Paratyphi A infection in healthy adults using a controlled human infection model, without any safety concerns.
Enteric fever, caused by Salmonella Typhi and Salmonella Paratyphi, leads to more than 100,000 deaths and over 8 million disability-adjusted life years each year. Around 30% of cases, over 2 million annually, are caused by S. Paratyphi A, for which no vaccine is currently available.
The phase 2b randomised, double-blind, placebo-controlled trial, conducted by the Oxford Vaccine Group (Department of Paediatrics, University of Oxford) at six UK sites, enrolled 72 healthy adult volunteers aged 18 to 55.
Participants received two oral doses of the CVD 1902 vaccine or a placebo, given 14 days apart. Four weeks after the second dose, they were deliberately exposed to S. Paratyphi A under carefully monitored conditions to assess protection.
Within 14 days of challenge, 21% of participants in the vaccine group and 75% in the placebo group were diagnosed with infection, equating to a vaccine efficacy of 73% (95% CI, 46–86).
No vaccine-related serious adverse events were identified, and side effects were generally mild to moderate in both groups.
Dr Naina McCann, Clinical Research Fellow at the Oxford Vaccine Group and lead author, said: “This is the first time a modern-day vaccine has been shown to protect people against Salmonella Paratyphi A, a disease that affects millions of people every year. By using a controlled human infection model, we were able to show that this vaccine was effective using only a small number of participants, greatly accelerating the path to a licensed vaccine.”
Professor Sir Andrew Pollard, Director of the Oxford Vaccine Group and co-senior author, said: "We are in a constant fight against bacterial infections, like paratyphoid, that threaten the lives of children in some of the most resource-poor regions of the world. This study provides hope that this important disease could be controlled by vaccination if the same effects can be obtained in real-life conditions in those communities"
Professor Xinxue Liu, Associate Professor of Medical Statistics and Epidemiology at the Oxford Vaccine Group and co-senior author, said: “While typhoid conjugate vaccines have been introduced in eight countries, there are no currently licensed vaccines for paratyphoid fever. Our study marks an important step toward developing paratyphoid vaccines as part of broader efforts to control enteric fever. Oxford is now conducting additional studies evaluating two new bivalent typhoid-paratyphoid conjugate vaccine candidates, aiming to accelerate progress toward comprehensive enteric fever prevention globally.”
The research was funded by the UK Medical Research Council (MRC) and the National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre, with collaboration from Bharat Biotech International Ltd. and the University of Maryland, where the vaccine was originally engineered.
The paper, “Safety, Efficacy, and Immunogenicity of a Salmonella Paratyphi A Vaccine,” by McCann et al., is published in The New England Journal of Medicine on 30th October 2025. Read the article here