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

Paratyphi A) is responsible for more than 2 million cases of enteric fever annually.

副伤寒A型每年导致超过200万例伤寒病例。

There are no licensed vaccines against S.

目前尚无针对沙门氏菌A型的批准疫苗。

Paratyphi A.

副伤寒A型。

Methods

In a double-blind, randomized, placebo-controlledtrial, we evaluated an orally administered live, attenuated S.

在一项双盲、随机、安慰剂对照试验中，我们评估了一种口服给药的活的、减毒的S。

Paratyphi A vaccine (CVD 1902) using a controlled human infection model.

伤寒沙门氏菌A疫苗（CVD 1902）使用了受控的人类感染模型。

Healthy U.K. adults were assigned in a 1:1 ratio to receive two doses of CVD 1902 or placebo 14 days apart.

健康英国成年人以1:1的比例被分配接受两剂CVD 1902或安慰剂，两次接种间隔14天。

Twenty-eight days after the second dose, participants were challenged orally with S.

在第二次接种后28天，参与者被口头挑战S。

Paratyphi A.

副伤寒A型。

The primary end point was a diagnosis of S.

主要终点是确诊为S。

Paratyphi A infection within 14 days after challenge.

在挑战后14天内发生副伤寒A感染。

Secondary end points included safety and immunogenicity.

次要终点包括安全性和免疫原性。

Results

A total of 72 participants underwent randomization, of whom 34 in the CVD 1902 group and 36 in the placebo group were challenged with S.

共有72名参与者进行了随机分组，其中CVD 1902组有34人，安慰剂组有36人接受了S. Paratyphi A的挑战。

Paratyphi A.

副伤寒A型。

The median age of the participants was 32 years (range, 20 to 54), and 46% were women.

参与者的中位年龄为32岁（范围，20至54岁），其中46%为女性。

The number of adverse events was generally similar in the two groups, and no vaccine-related serious adverse events were identified.

两组中不良事件的数量大致相似，且未发现与疫苗相关的严重不良事件。

CVD 1902 induced serum IgG and IgA responses to the O antigen of S.

CVD 1902诱导血清IgG和IgA对抗伤寒沙门氏菌A型O抗原的反应。

Paratyphi A.

副伤寒A型。

No increases in serum IgG or IgA titers occurred in the placebo group.

安慰剂组中血清IgG或IgA滴度未见增加。

In the intention-to-treatpopulation, an S.

在意向治疗人群中，一个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).

在CVD 1902组中，有21%的参与者在挑战后14天内被诊断出副伤寒A感染，而在安慰剂组中这一比例为75%（P<0.001），导致疫苗效力为73%（95% 置信区间[CI]，46至86）。

The vaccine efficacy was 69% (95% CI, 42 to 84) in the per-protocol analysis.

在按方案分析中，疫苗效力为69%（95% 置信区间[CI]，42至84）。

Conclusions

In healthy U.K. adults who were challenged with S.

在健康英国成年人中，通过受控人体感染模型挑战S. Paratyphi A，CVD 1902的两剂系列能够提供对S的保护。

Paratyphi A in a controlled human infection model, a two-dose series of CVD 1902 led to protection against S.

在受控的人类感染模型中，CVD 1902的两剂系列接种对副伤寒A型提供了保护。

Paratyphi A infection without safety concerns.

Paratyphi A感染没有安全问题。

(Funded by the Medical Research Council; VASP ISRCTN Registry number, 15485902.).

(由医学研究委员会资助；VASP ISRCTN注册号，15485902。)