TOPLINE:

An investigational oral, live-attenuated vaccine for Salmonella serovar Paratyphi A — CVD 1902 — provided significant protection against S Paratyphi A infection in healthy adults in a phase 2 controlled human challenge study, with no serious safety concerns observed.

METHODOLOGY:

• Researchers conducted a phase 2b randomized controlled trial to assess the safety and efficacy of the S Paratyphi A vaccine candidate, CVD 1902, in 72 healthy adults (median age, 32 years; 54% male) with no history of enteric fever.
• Participants were randomly assigned to receive either two 30-mL doses of CVD 1902 (minimum dose of 2 × 10¹⁰ colony-forming units; n = 34) or placebo (n = 36), administered 14 days apart.
• Approximately 28 days after the second dose, participants were orally challenged with 1 × 10³ to 5 × 10³ colony-forming units of wild-type S Paratyphi A strain.
• The primary endpoint was a diagnosis of S Paratyphi A infection within 14 days after the challenge, defined by prespecified composite criteria — a positive blood culture obtained more than 72 hours post-challenge or a ≥ 38 °C fever lasting at least 12 hours.
• Secondary endpoints included safety; immunogenicity, assessed using serum immunoglobulin G and immunoglobulin A antibody responses against O-lipopolysaccharide and flagellin antigens on days 14 and 42 after the first dose; and clinical and microbiologic outcomes after challenge.

TAKEAWAY:

• S Paratyphi A infection was diagnosed in 21% of vaccine recipients and 75% of placebo recipients (P < .001), corresponding to a vaccine efficacy of 73% (95% CI, 46-86); efficacy remained similar in analyses restricted to challenged participants.
• Serum immunoglobulin G and immunoglobulin A antibody levels against the O antigen rose above baseline on days 14 and 42 after the first vaccine dose but remained similar to those at baseline in the placebo group.
• Four serious adverse events occurred, with two in each group; none were considered related to the vaccine or placebo. Most solicited symptoms were mild to moderate.
• Among participants diagnosed with infection, clinical manifestations and microbiologic outcomes showed similar patterns between groups.

IN PRACTICE:

“CVD 1902 showed efficacy against S Paratyphi A in a controlled human infection model. These findings are a step toward a much-needed S Paratyphi A vaccine,” the authors of the study wrote.

SOURCE:

The study was led by Naina McCann, Oxford Vaccine Group, Department of Paediatrics, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, England. It was published online on October 30, 2025, in The New England Journal of Medicine.

LIMITATIONS:

The controlled human infection model was artificial in nature, and the study focused on healthy UK adults rather than the target population of school-age children in endemic areas. The formulation of CVD 1902 used in the trial requires same-day preparation, potentially limiting its suitability for routine clinical use.

DISCLOSURES:

The study was funded by the National Institute for Health and Care Research Oxford Biomedical Research Centre and the Medical Research Council. Some authors disclosed holding patents, receiving grants or contracts and travel support, or serving as consultants for multiple pharmaceutical companies and other organizations.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.