Chen Wilbur H, Barnes Robin S, Sikorski Michael J, Datar Reva, Sukhavasi Roohali, Liang Yuanyuan, Rapaka Rekha R, Pasetti Marcela F, Sztein Marcelo B, Wahid Rezwanul, Tennant Sharon M, Simon Raphael, Baliban Scott M, Galen James E, Lees Andrew, Bernshtein Biana, Alter Galit, Ella Raches, Mohan Krishna, Naidu M Gangadhara, Rao D Yogeswar, Ella Krishna M, Levine Myron M
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, U.S.A.
Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, U.S.A.
medRxiv. 2025 Sep 18:2025.09.15.25335795. doi: 10.1101/2025.09.15.25335795.
In sub-Saharan Africa, non-typhoidal (NTS) and Typhi are leading causes of invasive disease among young children. Trivalent Conjugate Vaccine (TSCV) consists of Vi capsule polysaccharide conjugated to tetanus toxoid and core-plus-O-polysaccharides from the two most prevalent invasive non-typhoidal serovars (Typhimurium, Enteritidis) conjugated to serovar-homologous flagellin subunits. We conducted a first-in-human, randomized, placebo-controlled, stepwise-dose-escalation phase 1 trial (NCT03981952) evaluating TSCV safety and immunogenicity; 22 healthy adults aged 18-45 years were randomly allocated 6.25 μg TSCV (n=8), 12.5 μg TSCV (n=10), or placebo (n=4). TSCV was safe and well-tolerated, with the most common solicited symptom being short-lived injection site pain. For each of the 3 polysaccharides, serum IgG and IgA ELISA antibody responses, as demonstrated by four-fold or greater increases over baseline, were observed among all vaccinees but among no placebo recipients. Binding and functional antibodies, gut-homing antibody secreting cells, and polysaccharide-specific memory B cells responses were also elicited. ClinicalTrials.gov Registry NCT03981952.
在撒哈拉以南非洲地区，非伤寒沙门氏菌（NTS）和伤寒杆菌是幼儿侵袭性疾病的主要病因。三价结合疫苗（TSCV）由与破伤风类毒素结合的Vi胶囊多糖以及来自两种最常见的侵袭性非伤寒血清型（鼠伤寒沙门氏菌、肠炎沙门氏菌）的核心加O多糖与血清型同源鞭毛蛋白亚基结合而成。我们开展了一项首次人体、随机、安慰剂对照、逐步递增剂量的1期试验（NCT03981952），以评估TSCV的安全性和免疫原性；22名年龄在18至45岁的健康成年人被随机分配接受6.25μg TSCV（n = 8）、12.5μg TSCV（n = 10）或安慰剂（n = 4）。TSCV安全且耐受性良好，最常见的自发症状是短暂的注射部位疼痛。对于这3种多糖中的每一种，所有疫苗接种者均观察到血清IgG和IgA ELISA抗体反应，较基线水平升高四倍或更多，但安慰剂接受者未出现这种情况。还引发了结合抗体和功能性抗体、归巢肠道的抗体分泌细胞以及多糖特异性记忆B细胞反应。ClinicalTrials.gov注册号：NCT03981952。
