An Oxford-led study has found that the oral live-attenuated vaccine CVD 1902 provides significant protection against Salmonella Paratyphi A infection in healthy adults. The research, conducted by the Oxford Vaccine Group at the University of Oxford’s Department of Paediatrics, used a controlled human infection model and reported no safety concerns.
Enteric fever, which is caused by Salmonella Typhi and Salmonella Paratyphi, results in more than 100,000 deaths each year and over 8 million disability-adjusted life years lost. S. Paratyphi A is responsible for about 30% of these cases—over 2 million annually—and currently there is no available vaccine for this strain.
The phase 2b randomized, double-blind, placebo-controlled trial took place at six sites across the UK. Seventy-two healthy adult volunteers between ages 18 and 55 participated in the study. Each participant received two oral doses of either CVD 1902 or a placebo, administered two weeks apart. Four weeks after the second dose, participants were deliberately exposed to S. Paratyphi A under close medical supervision to test vaccine efficacy.
Within two weeks following exposure, 21% of those who received the vaccine were diagnosed with infection compared to 75% in the placebo group. This equates to a vaccine efficacy rate of 73% (95% CI, 46–86). No serious adverse events related to the vaccine were reported; side effects were generally mild to moderate in both groups.
Dr Naina McCann, Clinical Research Fellow at the Oxford Vaccine Group and lead author of the study 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 added: "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 Oxford Vaccine Group and co-senior author commented: "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."
Funding for this research came from UK Medical Research Council (MRC) and National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre. Bharat Biotech International Ltd., along with University of Maryland—where CVD 1902 was first engineered—also collaborated on this work.
The full findings appear in The New England Journal of Medicine under "Safety, Efficacy, and Immunogenicity of a Salmonella Paratyphi A Vaccine".