Clinical study of safety and immunogenicity of pentavalent DTP-HB-Hib vaccine administered by disposable-syringe jet injector in India

Abstract

Introduction We conducted a randomized, observer-blind, non-inferiority, parallel-group clinical study of diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenzae type b conjugate (pentavalent) vaccination of infants in India. Goals were to determine whether the seropositivity rate after vaccination via disposable-syringe jet injector (DSJI) was non-inferior to that via needle and syringe (N-S), and to compare the safety of vaccination by the two methods. Methods Healthy children received a three-dose series of vaccine intramuscularly by DSJI or N-S beginning at 6–8 weeks of age. Immunoglobulin G antibody levels were measured by ELISA at 4–6 weeks after the third dose. The main secondary endpoint was safety, measured as injection site and systemic reactions. Discussion The study was stopped early out of caution beyond that specified in the protocol stopping criteria, after the Data Safety Committee noted a higher frequency of injection site reactions, especially moderate and severe, in the DSJI group. As a result, 128 subjects—DSJI group 61; N-S group 67—completed the study, rather than the 340 planned, and the study was not sufficiently powered to compare immunogenicity endpoints for the groups. Descriptive statistics indicate that seropositivity induced by vaccination with the DSJI was similar to that of N-S for all five antigens. Pentavalent vaccine includes whole-cell pertussis vaccine and an aluminum adjuvant, which may have contributed to the higher number of local reactions with the DSJI. The reactions caused no serious or long-term sequelae, and may be more acceptable in other populations or circumstances. US National Institutes of Health clinical trials identifier: NCT02409095.

Immunogenicity and Complications of the Pentavalent Vaccine in Iranian Children

“…In our study, 41.2% of the infants were immune against pertussis before vaccination (maternal immunity), which increased to 63.7% 1 month after the third dose of the vaccine. This result was similar to the study of (8). In the study of (15) 6 months after the third dose of the Pentavalent vaccine, 17.3% had pertussis immunity (15).…”

“…The first combination vaccine was used in children in 1940 (6). Five antigens are currently available as a Pentavalent combination vaccine for protection against tuberculosis, diphtheria, tetanus, whooping cough, poliomyelitis, and measles, as well as HepB and Hib in the national immunization program in developing countries (7,8). According to the WHO, vaccines are one of the most powerful tools in public health and more children are now being immunized than ever before (9).…”

Vaccination into the Dermal Compartment: Techniques, Challenges, and Prospects

“…The Pharmajet Stratis, a disposable-syringe jet injector, has been assessed in a clinical trial (NCT02253407) in India. It was shown that similar levels of seroconversion were observed after measles, mumps, and rubella (MMR) vaccination by jet injector as with needle and syringe injection in 170 toddlers 35 days post-injection, as well as similar adverse effect rates [ 178 ]. However, another trial (NCT02409095) in India with the same disposable-syringe jet injector but for DTP-HB-Hib vaccination had to be prematurely terminated after a higher frequency of injection site reaction was observed in those treated with the jet injector compared to those injected by needle and syringe.…”

Recent Advances in Micro-Electro-Mechanical Devices for Controlled Drug Release Applications

“…In this context, in addition to microneedle-based technology previously exposed, some needle-free systems also aimed at solving these problems were developed. Needle-free jet injectors are currently one of the effective alternatives to conventional needle injections, with multiple commercial devices cited in clinical trials ( Bremseth and Pass, 2001 ; Yousafzai et al, 2017 ; Bavdekar et al, 2019 ). TDD based on this mechanism entails ejection of a liquid drug through a fine nozzle at elevated pressure, thus generating a narrow super-fast fluid jet easily penetrable into the skin and tissue ( Figure 12 ).…”