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Safety and Immunogenicity of a Bivalent Paratyphoid A-Typhoid Conjugate Vaccine in Healthy Indian Adults: A Phase I, Randomized, Active Controlled Study
26 Pages Posted: 28 Aug 2023
More...Abstract
Background: Enteric fever caused by Salmonella Typhi and Paratyphi A is an important public health problem, especially in low- and middle-income countries with limited access to safe water and sanitation. Phase I results from a first ever human study of a bivalent Paratyphoid A-Typhoid Conjugate Vaccine (Sii-PTCV) are presented.
Methods: Sixty healthy adults randomized in a 1:1 ratio received a single dose of either Sii-PTCV or Typbar-TCV® by intramuscular route. Safety was assessed by observing solicited adverse events for 1-week, unsolicited events for 1-month and serious adverse events (SAE) over 6 months. Immunogenicity at 1 and 6 months was assessed by measuring anti-Vi IgG and IgA against S. Typhi and anti-lipopolysaccharide IgG against S. Paratyphi A by ELISA, and functional antibodies using serum bactericidal assay (SBA) against S. Paratyphi A.
Findings: Solicited events were observed in 90% of participants in Sii-PTCV and 86.7% in Typbar-TCV® groups. No vaccine-related unsolicited AEs or SAEs were reported. Typhoid seroconversion rates at one-month in both groups for IgG and IgA anti-Vi antibodies were 93.3% or higher, with fold-rise of 171.25 or higher for IgG and 43.27 or higher for IgA. Paratyphoid seroconversion rates at one-month with Sii-PTCV for IgG antibodies and SBA titres were 93.3% or higher, with fold-rise of 80 for IgG and 19.4 for SBA. Paratyphoid anti-LPS immune responses were sustained at 6 months. Typbar-TCV® did not develop immune response to paratyphoid.
Interpretation: Sii-PTCV was safe and immunogenic for both typhoid and paratyphoid antigens indicating potential for comprehensive protection against enteric fever.
Trial Registration: CTRI/2022/06/043608.
Funding: The study was funded by Serum Institute of India Pvt. Ltd., Pune, India.
Declaration of Interest: PSK, AVP, SB, AD, VG, CK, ADS, SG, and SSP are employees of Serum Institute of India Pvt. Ltd. (SIIPL). CSP is the chairman and managing director of SIIPL. AJP is chair of DHSC’s Joint Committee on Vaccination and Immunisation and was a member of WHOs SAGE until 2022. AJP and AF are contributors to intellectual property licensed by Oxford University Innovation to AstraZeneca on COVID19 vaccines. AJP has received COVID19 vaccine consulting fees from Shionogi. He has received grants on typhoid and paratyphoid vaccines from the Bill & Melinda Gates Foundation, the UK Medical Research Council and the Wellcome Trust. Other authors have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Ethical Approval: Approval from Indian regulatory authority and Sri Venkateshwara Hospital Ethics Committee. Participants were screened after obtaining written informed consent.
Keywords: Enteric fever, typhoid, paratyphoid, first-in-human
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