Safety, Efficacy, and Immunogenicity of a Salmonella Paratyphi A Vaccine.

BackgroundSalmonella enterica serovar Paratyphi A (also known as S. Paratyphi A) is responsible for more than 2 million cases of enteric fever annually. There are no licensed vaccines against S. Paratyphi A.MethodsIn a double-blind, randomized, placebo-controlled trial, we evaluated an orally administered live, attenuated S. Paratyphi A vaccine (CVD 1902) using a controlled human infection model. Healthy U.K. adults were assigned in a 1:1 ratio to receive two doses of CVD 1902 or placebo 14 days apart. Twenty-eight days after the second dose, participants were challenged orally with S. Paratyphi A. The primary end point was a diagnosis of S. Paratyphi A infection within 14 days after challenge. Secondary end points included safety and immunogenicity.ResultsA total of 72 participants underwent randomization, of whom 34 in the CVD 1902 group and 36 in the placebo group were challenged with S. Paratyphi A. The median age of the participants was 32 years (range, 20 to 54), and 46% were women. The number of adverse events was generally similar in the two groups, and no vaccine-related serious adverse events were identified. CVD 1902 induced serum IgG and IgA responses to the O antigen of S. Paratyphi A. No increases in serum IgG or IgA titers occurred in the placebo group. In the intention-to-treat population, an S. Paratyphi A infection was diagnosed within 14 days after challenge in 21% of the participants in the CVD 1902 group and in 75% of those in the placebo group (P<0.001), resulting in a vaccine efficacy of 73% (95% confidence interval [CI], 46 to 86). The vaccine efficacy was 69% (95% CI, 42 to 84) in the per-protocol analysis.ConclusionsIn healthy U.K. adults who were challenged with S. Paratyphi A in a controlled human infection model, a two-dose series of CVD 1902 led to protection against S. Paratyphi A infection without safety concerns. (Funded by the Medical Research Council; VASP ISRCTN Registry number, 15485902.).