The safety and immunogenicity of a bivalent conjugate vaccine against Salmonella enterica Typhi and Paratyphi A in healthy Indian adults: a phase 1, randomised, active-controlled, double-blind trial
04/2024
Journal Article
Authors:
Kulkarni, P. S.;
Potey, A. V.;
Bharati, S.;
Kunhihitlu, A.;
Narasimha, B.;
Yallapa, S.;
Dharmadhikari, A.;
Gavade, V.;
Kamat, C. D.;
Mallya, A.;
Sarma, A. D.;
Goel, S.;
Pisal, S. S.;
Poonawalla, C. S.;
Venkatesan, R.;
Jones, E.;
Flaxman, A.;
Kim, Y. C. ;
Pollard, A. J.;
T. C. V. Study Group
Journal:
Lancet
PMID:
38555928
URL:
https://www.ncbi.nlm.nih.gov/pubmed/38555928
DOI:
10.1016/S0140-6736(24)00249-6
Keywords:
Enteric fever Salmonella enterica Typhi Salmonella Paratyphi A
Abstract:
BACKGROUND: Enteric fever caused by Salmonella enterica Typhi and Salmonella Paratyphi A is an important public health problem, especially in low-income and middle-income countries with limited access to safe water and sanitation. We present results from, to our knowledge, the first ever human study of a bivalent paratyphoid A-typhoid conjugate vaccine (Sii-PTCV). METHODS: In this double-blind phase 1 study, 60 healthy Indian adults were randomly assigned (1:1) to receive a single intramuscular dose of either Sii-PTCV or typhoid conjugate vaccine (Typbar-TCV). Safety was assessed by observing solicited adverse events for 1 week, unsolicited events for 1 month, and serious adverse events (SAEs) over 6 months. Immunogenicity at 1 month and 6 months was assessed by measuring anti-capsular polysaccharide antigen Vi (anti-Vi) IgG and IgA against Salmonella Typhi and anti-lipopolysaccharide (LPS) IgG against Salmonella Paratyphi A by ELISA, and functional antibodies using serum bactericidal assay (SBA) against Salmonella Paratyphi A. This study is registered with Clinical Trial Registry-India (CTRI/2022/06/043608) and is completed. FINDINGS: 60 participants were enrolled. Of these 60 participants, 57 (95%) participants were male and three (5%) participants were female. Solicited adverse events were observed in 27 (90%) of 30 participants who received Sii-PTCV and 26 (87%) of 30 participants who received Typbar-TCV. The most common local solicited event was pain in 27 (90%) participants who received Sii-PTCV and in 23 (77%) participants who received Typbar-TCV. The most common solicited systemic event was myalgia in five (17%) participants who received Sii-PTCV, whereas four (13%) participants who received Typbar-TCV had myalgia and four (13%) had headache. No vaccine-related unsolicited adverse events or SAEs were reported. The seroconversion rates on day 29 were 96.7% (95% CI 82.8-99.9) with Sii-PTCV and 100.0% (88.4-100.0) with Typbar-TCV for anti-Vi IgG; 93.3% (77.9-99.2) with Sii-PTCV and 100.0% (88.4-100.0) with Typbar-TCV for anti-Vi IgA; 100.0% (88.4-100.0) with Sii-PTCV and 3.3% (0.1-17.2) with Typbar-TCV for anti-LPS (paratyphoid); and 93.3% (77.9-99.2) with Sii-PTCV and 0% (0.0-11.6) with Typbar-TCV for SBA titres (paratyphoid). Paratyphoid anti-LPS immune responses were sustained at day 181. INTERPRETATION: Sii-PTCV was safe and immunogenic for both typhoid and paratyphoid antigens indicating its potential for providing comprehensive protection against enteric fever. FUNDING: Serum Institute of India.
