AUTHORS
Wilbur H. Chen, Robin S. Barnes, Michael J. Sikorski, Reva Datar, Roohali Sukhavasi, Yuanyuan Liang, Rekha R. Rapaka, Marcela F. Pasetti, Marcelo B. Sztein, Rezwanul Wahid, Sharon M. Tennant, Raphael Simon, Scott M. Baliban, James E. Galen, Andrew Lees, Biana Bernshtein, Galit Alter, Raches Ella, Krishna Mohan, M. Gangadhara Naidu, D. Yogeswar Rao, Krishna M. Ella & Myron M. Levine
ABSTRACT
In sub-Saharan Africa, typhoidal and non-typhoidal Salmonella (NTS) are leading causes of invasive disease among young children. Trivalent Salmonella conjugate vaccine (TSCV) consists of Vi capsule polysaccharide conjugated to tetanus toxoid and core-plus-O-polysaccharides from the two most prevalent invasive NTS serovars conjugated to flagellin subunits. We conducted a first-in-human, randomized, placebo-controlled, phase 1 trial evaluating the safety and immunogenicity of TSCV. A total of 22 healthy adults aged 18−45 years were randomly allocated to 6.25-µg TSCV (n = 8), 12.5-µg TSCV (n = 10) or placebo (n = 4). The primary objective was the assessment of safety. The co-primary immunogenicity objective was the serum IgG response against the three vaccine polysaccharides and two flagellin carrier proteins. Here we show that TSCV was safe and well tolerated, meeting the prespecified safety endpoints, with the most common solicited symptom being short-lived injection site pain. For each of the three polysaccharides, immune responses, as demonstrated by ≥4-fold increases over baseline, were observed among all (100%) vaccinees, and no responses were elicited in the placebo group, meeting the prespecified immunogenicity endpoints. The two flagellin components elicited 88% (7/8) and 100% (8/8) responses among 6.25-µg and 12.5-µg TSCV recipients and no placebo recipients. These data warrant further evaluation of TSCV for protection against invasive Salmonella disease. ClinicalTrial.gov identifier: NCT03981952.
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