A randomized Phase I/II study to evaluate safety and reactogenicity of a heat-stable rotavirus vaccine in healthy adults followed by evaluation of the safety, reactogenicity, and immunogenicity in infants

Abstract

Objectives: To assess the safety and reactogenicity of single oral dose of heat-stable rotavirus vaccine (HSRV) in healthy adults aged 18-45 years followed by assessment of safety, reactogenicity, and immunogenicity of three doses of HSRV in healthy infants aged 6-8 weeks at enrollment. Trial Design: Single-center randomized controlled, sequential, blinded (adults) and open-label (infants). Setting: Single site at International Center for Diarrheal Disease Research, Bangladesh (icddr,b). Participants: Fifty eligible adults randomized in 1:1 ratio (HSRV: Placebo) followed by 50 eligible infants randomized in 1:1 ratio (HSRV: Comparator (RotaTeq®, pentavalent human-bovine (WC3) reassortant liveattenuated, rotavirus vaccine)). Intervention: Adults received either a single dose of HSRV or placebo and followed for 14 days. Infants received three doses of either HSRV or comparator with a follow-up for 28 days after each dose. Main Outcome Measures: Solicited and unsolicited adverse events (AEs) along with any serious adverse events (SAEs) were part of the safety and reactogenicity assessment in adults and infants whereas serum anti-rotavirus IgA response rates were part of immunogenicity assessment in infants only. Postvaccination fecal shedding of vaccine-virus rotavirus strains was also determined in adults and infants. Results: In this study, HSRV, when compared with placebo, did not result in increase in solicited adverse events (solicited AEs) in adults. In infants, HSRV had a safety profile similar to comparator vis-à-vis solicited AEs. In infants, fecal shedding of vaccine-virus strains was not detected in HSRV recipients but was observed in two comparator recipients. Percentage of infants exhibiting threefold rise in serum antirotavirus IgA titers from baseline to 1-month post-dose 3 in HSRV group was 88% (22/25) and 84% (21/ 25) in comparator group. Conclusion: HSRV was found to be generally well-tolerated in both adults and infants and immunogenic in infants.

Human rotavirus strains circulating among children in the capital of China (2018–2022)_ predominance of G9P[8] and emergence ofG8P[8]

“…Here, we reported the first detection of RotaTeq vaccine strain from RVGE patients after it was imported to China. As reported, for live RV vaccines, vaccine-virus shedding occurs in approximately 5%–10% of the recipients after the first dose and very rarely thereafter [ 12 , 44 , 45 ]. With the rapid increasing lot-release of RotaTeq vaccine imported to China, the shedding of vaccine virus strains should be continuously monitored.…”

Clinical and Preclinical Methods of Heat-Stabilization of Human Vaccines

“…This displayed that alternative storage schedules are viable for live-attenuated, inactivated, and subunit-conjugate vaccines and indicates that changes in storage should be more readily evaluated clinically. National clinical trial number 02728869 (NCT02728869) , developed a heat stable live-attenuated oral rotavirus (HSRV) vaccine based on the FDA-approved RotaTeq vaccine. To identify a heat-stable formulation, they first iterated preclinically using different buffering agents, bulking agents, cryoprotectants, amino acids, and cations to identify a stabilized vaccine containing HEPES buffer, sucrose, polyvinylpyrrolidone, l -arginine, and calcium chloride dihydrate .…”

Rotavirus Vaccine Trials in International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) and Future Use of the Vaccine in Bangladesh

“…We also compared a new heat-stable formulation of lyophilized live-attenuated pentavalent rotavirus vaccine (HSRV)— manufactured by MSD Wellcome Trust Hilleman Laboratories (New Delhi, India) with RotaTeq—in a randomized Phase I/II among infants living in urban slum, which was the first trial of its kind. The HSRV was found to be safe and immunogenic (88% seroresponse rate) [ 8 ]. This heat-stable rotavirus vaccine can be sustained at 45°C for 7 months, and this is important for resource-limited settings where most of the rotavirus burden exists and maintaining a cold chain is challenging.…”

“…This heat-stable rotavirus vaccine can be sustained at 45°C for 7 months, and this is important for resource-limited settings where most of the rotavirus burden exists and maintaining a cold chain is challenging. Our study generates new data on newer rotavirus vaccine formulations that can partially or entirely eliminate cold chain dependence and reduce associated costs [ 8 ].…”