Research Article: Six-month follow up of a randomized clinical trial-phase I study in Indonesian adults and children: Safety and immunogenicity of Salmonella typhi polysaccharide-diphtheria toxoid (Vi-DT) conjugate vaccine

Date Published: February 13, 2019

Publisher: Public Library of Science

Author(s): Bernie Endyarni Medise, Soedjatmiko Soedjatmiko, Iris Rengganis, Hartono Gunardi, Rini Sekartini, Sukamto Koesno, Hindra Irawan Satari, Sri Rezeki Hadinegoro, Jae Seung Yang, Jean-Louis Excler, Sushant Sahastrabuddhe, Mita Puspita, Rini Mulia Sari, Novilia Sjafri Bachtiar, Ray Borrow.

http://doi.org/10.1371/journal.pone.0211784

Abstract

There is a high global incidence of typhoid fever, with an annual mortality rate of 200,000 deaths. Typhoid fever also affects younger children, particularly in resource-limited settings in endemic countries. Typhoid vaccination is an important prevention tool against typhoid fever. However, the available polysaccharide typhoid vaccines are not recommended for children under 2 years of age. A new typhoid conjugate Vi-diphtheria toxoid (Vi-DT) vaccine has been developed for infant immunization. We aimed to define the safety and immunogenicity of the Vi-DT vaccine among adults and children in Indonesia.

An observational, blinded, comparative, randomized, phase I safety study in two age de-escalating cohorts was conducted in East Jakarta, Indonesia, from April 2017 to February 2018. We enrolled 100 healthy subjects in 2 age groups: adults and children (18–40 and 2–5 years old). These groups were randomized into study groups (Vi-DT vaccine), and comparator groups (Vi-polysaccharide (Vi-PS) vaccine and another additional vaccine) which was administered in 4 weeks apart. Subjects were followed up to six months.

One hundred healthy adults and children subjects completed the study. The Vi-DT and Vi-PS vaccines showed no difference in terms of intensity of any immediate local and systemic events within 30 minutes post-vaccination. Overall, pain was the most common local reaction, and muscle pain was the most common systemic reaction in the first 72 hours. No serious adverse events were deemed related to vaccine administration. The first and second doses of the Vi-DT vaccine induced seroconversion and higher geometric mean titers (GMT) in all subjects compared to that of baseline. However, in terms of GMT, the second dose of Vi-DT did not induce a booster response.

The Vi-DT vaccine is safe and immunogenic in adults and children older than two years. A single dose of the vaccine is able to produce seroconversion and high GMT in all individuals.

Partial Text

Typhoid fever remains a serious systemic infection and a public health threat throughout the world, particularly in resource-limited settings and countries, including some parts of Indonesia, which lack of clean drinking water, hygiene, and good sanitation. This enteric disease is caused by Salmonella enterica serovar typhi and spreads through the fecal-oral route.[1–4] Although mostly endemic, S. typhi has epidemic potential and causes 60% to 80% of typhoid infections in humans.[1,4–6]

Although typhoid vaccination is not yet a part of Indonesia’s Expanded Program for Immunization (EPI), the Indonesian Pediatric Society (IPS) immunization schedule still recommends all 2 years old children to receive the typhoid Vi-PS vaccine with booster doses every three years.[26,27] However, a study in two sub-districts of North Jakarta, Indonesia reported that the implementation of a large-scale, school-based typhoid Vi-PS vaccination campaign was logistically feasible, safe, and minimally disruptive to regular school activities, and had high rates of parental acceptance.[28]

Our phase I study suggests that the Vi-DT vaccine is safe and immunogenic in adults and children older than two years. A single dose of the vaccine is able to produce seroconversion and high GMT in all individuals.

 

Source:

http://doi.org/10.1371/journal.pone.0211784

 

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