Ibarz-Pavon Ana Belen, Bielsky Marie-Christine, Bose Rubina, Cavaleri Marco, Crump John A, Hombach Joachim, Kaslow David C, Khaman Farhana, MacLennan Calman A, Mehring-LeDoare Kirsty, Pollard Andrew J, Quadri Firdausi, John Jacob, Wilder-Smith Annelies
World Health Organization, Department of Immunization, Vaccines and Biologicals, Geneva, Switzerland.
Medicines and Healthcare products Regulatory Agency (MHRA), London, UK.
Vaccine. 2025 May 22;56:127189. doi: 10.1016/j.vaccine.2025.127189. Epub 2025 May 1.
Enteric fever caused by Salmonella enterica serovars Typhi and Paratyphi A and, to a lesser extent, S. Paratyphi B and C, remains a significant cause of mortality and morbidity in resource-constrained settings. Typhoid conjugate vaccines (TCVs) protect against S. Typhi but no vaccine to date protects against paratyphoid fever. There are several bivalent S. Typhi/Paratyphi A products in development; however, the low incidence of paratyphoid fever in many settings limits the feasibility of phase 3 efficacy studies. Two bivalent vaccines adding the S. Paratyphi A-specific O:2 lipopolysaccharide conjugated to a protein carrier to TCV constructs have successfully completed phase 1 studies and will progress rapidly in their development. The WHO's Product Development for Vaccines Advisory Committee (PDVAC) endorsed a regulatory pathway for a bivalent S. Typhi/Paratyphi A vaccine that contemplates demonstrating protective efficacy against S. Paratyphi A infection in a controlled human infection model (CHIM). Since the use of CHIM data in lieu of phase 3 efficacy studies and to identify markers of immune protection is not yet widely accepted by regulatory bodies, the WHO organized a consultation with vaccine developers, manufacturers, and regulators. The purpose of the meeting was to discuss the feasibility and considerations for the licensure of a bivalent S. Typhi/Paratyphi A vaccine. The aim of the consultation was to gain alignment among key stakeholders and facilitate the pathway to licensure in endemic countries.
由伤寒沙门氏菌血清型伤寒杆菌和甲型副伤寒杆菌，以及在较小程度上由乙型和丙型副伤寒杆菌引起的肠热病，在资源有限的环境中仍然是导致死亡和发病的重要原因。伤寒结合疫苗（TCV）可预防伤寒杆菌，但迄今为止尚无疫苗可预防副伤寒热。目前有几种二价伤寒杆菌/甲型副伤寒杆菌产品正在研发中；然而，在许多环境中副伤寒热的低发病率限制了3期疗效研究的可行性。两种二价疫苗在TCV构建体中添加了与蛋白质载体偶联的甲型副伤寒杆菌特异性O:2脂多糖，已成功完成1期研究，并将在其研发中迅速推进。世界卫生组织疫苗产品开发咨询委员会（PDVAC）认可了一种二价伤寒杆菌/甲型副伤寒杆菌疫苗的监管途径，该途径考虑在受控人类感染模型（CHIM）中证明对甲型副伤寒杆菌感染的保护效力。由于监管机构尚未广泛接受使用CHIM数据代替3期疗效研究并确定免疫保护标志物，因此世界卫生组织组织了一次疫苗开发者、制造商和监管机构的协商会议。会议的目的是讨论二价伤寒杆菌/甲型副伤寒杆菌疫苗许可的可行性和注意事项。协商的目的是使关键利益相关者达成一致，并促进在流行国家获得许可的途径。
