Novel Live Attenuated Vaccine to Prevent Salmonella Paratyphi Enteric Fever
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on November 24th, 2025
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Enteric fever caused by Salmonella enterica can be largely prevented through improved water and sanitation systems. Vaccination against the typhi serotype—the agent responsible for typhoid fever—has played a major role in reducing disease burden. However, no licensed vaccine has been available for the paratyphi serotype. With support from the United Kingdom’s Medical Research Council, researchers conducted a study to evaluate CVD 1902, a new vaccine designed to protect against Salmonella Paratyphi A.
The clinical trial enrolled 72 healthy volunteers in the United Kingdom, ages 18 to 55, with no prior history of enteric fever. Participants were randomly assigned to receive two oral doses of either CVD 1902 or a placebo, spaced 14 days apart. To reduce stomach acidity prior to vaccination, each participant drank 120 mL of sodium bicarbonate solution one minute before receiving the dose. CVD 1902 is a live attenuated vaccine containing over 20 billion colony-forming units of S. Paratyphi A engineered with deletions in the guaBA operon and clpX gene. This genetic engineering attempt reduce bacterial pathogenesis by interrupting the synthesis of guanine nucleotides, flagella motility and host cell invasion.
At 14 and 42 days after the first dose, investigators observed strong IgG and IgA antibody responses to the O antigen of S. Paratyphi A among those who received the vaccine, while no significant antibody changes were seen in the placebo group. Four weeks after the second dose, all participants underwent an oral challenge with a virulent wild-type S. Paratyphi A strain. Within 14 days of challenge, 75% of placebo recipients developed enteric fever, compared to only 25% of vaccine recipients. These findings correspond to a vaccine efficacy of 69%.
The clinical trial enrolled 72 healthy volunteers in the United Kingdom, ages 18 to 55, with no prior history of enteric fever. Participants were randomly assigned to receive two oral doses of either CVD 1902 or a placebo, spaced 14 days apart. To reduce stomach acidity prior to vaccination, each participant drank 120 mL of sodium bicarbonate solution one minute before receiving the dose. CVD 1902 is a live attenuated vaccine containing over 20 billion colony-forming units of S. Paratyphi A engineered with deletions in the guaBA operon and clpX gene. This genetic engineering attempt reduce bacterial pathogenesis by interrupting the synthesis of guanine nucleotides, flagella motility and host cell invasion.
At 14 and 42 days after the first dose, investigators observed strong IgG and IgA antibody responses to the O antigen of S. Paratyphi A among those who received the vaccine, while no significant antibody changes were seen in the placebo group. Four weeks after the second dose, all participants underwent an oral challenge with a virulent wild-type S. Paratyphi A strain. Within 14 days of challenge, 75% of placebo recipients developed enteric fever, compared to only 25% of vaccine recipients. These findings correspond to a vaccine efficacy of 69%.