Immunogenicity, safety and reactogenicity of a Phase II trial of Vi-DT typhoid conjugate vaccine in healthy Filipino infants and toddlers: A preliminary report

Maria Rosario Capeding, Edison Alberto, Arijit Sil, Tarun Saluja, Samuel Teshome, Deok Ryun Kim, Ju Yeon Park, Jae Seung Yang, Suchada Chinaworapong, Jiwook Park, Sue-Kyoung Jo, Yun Chon, Seon-Young Yang, Dong Soo Ham, Ji Hwa Ryu, Julia Lynch, Jerome H Kim, Hun Kim, Jean-Louis Excler, T Anh Wartel, Sushant Sahastrabuddhe, Maria Rosario Capeding, Edison Alberto, Arijit Sil, Tarun Saluja, Samuel Teshome, Deok Ryun Kim, Ju Yeon Park, Jae Seung Yang, Suchada Chinaworapong, Jiwook Park, Sue-Kyoung Jo, Yun Chon, Seon-Young Yang, Dong Soo Ham, Ji Hwa Ryu, Julia Lynch, Jerome H Kim, Hun Kim, Jean-Louis Excler, T Anh Wartel, Sushant Sahastrabuddhe

Abstract

Background: Typhoid fever remains an important public health problem in developing countries and is endemic in many parts of Asia and Africa where the incidence of disease typically peaks in school-aged children. Age restrictions and other limitations of existing oral live-attenuated typhoid and parenteral Vi polysaccharide vaccines have triggered the development of Vi conjugate vaccines with improved immunological properties, use in younger age range, and longer durability of protection. We present the safety, reactogenicity, and immunogenicity data from a Phase II study after a single dose of Vi polysaccharide conjugated to diphtheria toxoid (Vi-DT) conducted in 6-23-month old Filipino children.

Methods: This is a randomized, observer-blinded Phase II study to assess the immunogenicity, safety and reactogenicity of Vi-DT compared to placebo, conducted in Muntinlupa City, The Philippines. Participants aged 6-23 months were enrolled and randomized to Vi-DT (25 µg) or placebo (0.9% sodium chloride) and evaluated for immunogenicity and overall safety 28 days post vaccination.

Results: A total of 285 participants were enrolled and age-stratified: 6 to < 9 months, 9-12 months, and 13-23 months. Seventy-six (76) participants received Vi-DT and 19 received placebo per each strata. All participants seroconverted after a single dose of Vi-DT versus 7% of placebo recipients. Anti-Vi IgG GMT was 444.38 [95% CI (400.28; 493.34)] after a single dose of Vi-DT; there was no change in GMT after placebo administration, 0.41 [95% CI (0.33; 0.51), p < 0.0001]. A similar pattern of immunogenicity was reported across all age strata. The vaccine reported to be safe and well tolerated.

Conclusions: Vi-DT vaccine was immunogenic, safe, and well tolerated in children aged 6-23 months. ClinicalTrials.gov registration number: NCT03527355.

Keywords: Immunogenicity; Infants; Philippines; Safety; Toddlers; Typhoid conjugate vaccine; Typhoid fever; Vi-DT.

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflicts of Interest Maria Rosario Capeding received research grant. Seon-young Yang, Dong Soo Ham, Ji Hwa Ryu, and Hun Kim are employees of SK bioscience. Dr. Jerome Kim has consulted for Takeda and served as an unpaid consultant for GSK. All other authors declare having no conflict of interest.

Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1
Fig. 1
Flow diagram of Participant Disposition (CONSORT flow diagram). Age Strata 1: 6 to less than 9 months; Age Strata 2: 9–12 months; Age Strata 3: 13–23 months.
Fig. 2
Fig. 2
Seroconversion rates as measured by anti-Vi IgG ELISA Response. [Note] Seroconversion rate is proportion of participants who had 4-fold rise in titers compared to baseline (Day 0, Week 0) to post dose. Among all participants the difference in seroconversions post single dose compared to the placebo group was statistically significant (P 

Fig. 3

GMT of anti-Vi IgG ELISA…

Fig. 3

GMT of anti-Vi IgG ELISA response. [Note] Among all participants the difference in…

Fig. 3
GMT of anti-Vi IgG ELISA response. [Note] Among all participants the difference in GMT comparing Vi-DT to placebo was statistically significant (p 
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Fig. 3
Fig. 3
GMT of anti-Vi IgG ELISA response. [Note] Among all participants the difference in GMT comparing Vi-DT to placebo was statistically significant (p 

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