A novel Vi-diphtheria toxoid typhoid conjugate vaccine is safe and can induce immunogenicity in healthy Indonesian children 2–11 years: a phase II preliminary report

Abstract

Background Typhoid fever caused by Salmonella enteric serovar Typhi (S. Typhi) is a common cause of morbidity in the world. In 2017, 14.3 million cases of Typhoid and paratyphoid fever occurred globally. School age children between 3 to 19 years old are the most affected. Poor sanitation and multi drug resistance have increased the need for vaccines to reduce the global burden of disease. Based on previous trials, typhoid conjugate vaccines have longer- lasting protection, higher efficacy, require fewer doses and are suitable from infancy that allows them to be incorporated into the routine immunization program. Our previous phase I trial proved that a novel Vi-DT typhoid conjugate vaccine is safe and immunogenic in subjects 2–5 and 18–40 years. Our phase II trial consisted of subjects 6 months to 40 years. Our previously published paper on subjects 6 to < 24 months proved that this vaccine is safe and immunogenic for this age group. Therefore, with this paper we aimed to evaluate the safety and immunogenicity in children 2–11 years. Methods A randomized, observer-blind, superiority design of Vi-DT Typhoid conjugate vaccine compared to Vi-polysaccharide vaccine (Vi-PS) phase II study was conducted from October 2018 to December 2018 where 200 subjects aged 2–11 years were recruited. A blood sample prior to vaccination was taken, followed by administration of a single dose of either test vaccine (Vi-DT) or control vaccine (Vi-PS) and then a second blood sample was collected 28 days post vaccination. Adverse reactions were assessed and antibody increment was evaluated at 28 days post vaccination through collected serum sample. Results Pain was the most common local reaction. Fever and muscle pain were the most common systemic reactions. Both Vi-DT and Vi-PS groups had roughly the same number of adverse reactions. At 28 days post vaccination, 100% of subjects in the Vi-DT group and 93% of subjects in the Vi-PS group produced antibody increment ≥4 times. The Vi-DT group produced a higher GMT as compared to Vi-PS. Conclusion Vi-DT vaccine is safe and immunogenic in children 2–11 years old. Trial registration Trial registration number: NCT03460405.

Optimalisasi 1000 Hari Pertama Kehidupan: Nutrisi, Kasih Sayang, Stimulasi, dan Imunisasi Merupakan Langkah Awal Mewujudkan Generasi Penerus yang Unggul

“…37 Uji klinis vaksin lainnya adalah imunogenisitas dan keamanan vaksin influenzae trivalen, 38 keamanan dan imunogenisitas polisakarida Salmonella typhi konjugasi dengan toksoid difteri, fase 1 dan fase 2 yang dapat diberikan pada anak mulai usia 9 bulan. 39,40…”

A TLR4 ligand-based adjuvant for promoting the immunogenicity of Typhoid subunit vaccines

“…The TCVs utilize a variety of carrier proteins e.g. recombinant Exoprotein A from P. aeruginosa (8), CRM197, a non-toxic mutant of diphtheria toxin (9), tetanus toxoid (10), or diphtheria toxoid (11) chemically coupled to ViPS.…”

Identification of collaborative cross mouse strains permissive to Salmonella enterica serovar Typhi infection

“…S. Typhi expresses Vi polysaccharide (ViPS), a well-known virulence factor 4 , 5 and is a target for protective immune responses 3 , 6 . Three types of vaccines are currently available: (1) live attenuated vaccine, (2) subunit vaccines composed of plain ViPS 7 , 8 and, (3) ViPS conjugated to a variety of carrier proteins such as rEPA, a recombinant Exoprotein A from P. aeruginosa 9 , CRM197, a non-toxic mutant of diphtheria toxin 10 , tetanus toxoid 11 , or diphtheria toxoid 12 .…”