Immunogenicity of a human rotavirus vaccine (RIX4414) after storage at 37 °C for seven days

Abstract

Aim: The lyophilized formulation of the human rotavirus vaccine, RIX4414 (RotarixTM), is recommended to be stored at 2°C-8°C for optimal immunogenicity. In some settings with inadequate infrastructure for vaccine storage, unforeseen circumstances may cause cold chain breakage, resulting in the vaccine to be left at ambient temperatures. This study evaluated the heat stability of lyophilized RIX4414 vaccine in terms of immunogenicity when stored at tropical room temperature (37 °C) for 7 days before reconstitution.

Results: There was no statistically significant difference detected between RIX4414 vaccine stored at 2 °C-8 °C (Group RIX4414_control, n = 171) and that stored at 37 °C for 7 days (Group RIX4414_37 °C, n = 47) in terms of seroconversion rate and vaccine take. The anti-rotavirus IgA seroconversion rate 2 months post-Dose 2 was 84.7% (95% CI: 78.1%-90%) and 87.8% (95% CI: 73.8%-95.9%) in Groups RIX4414_control and RIX4414_37 °C, respectively. None of the 25 infants in placebo group seroconverted. The vaccine take in the respective vaccine groups were 88% (95% CI: 82.1%-92.5%) and 93.5% (95% CI: 82.1%-98.6%) and Geometric Mean Concentrations (GMCs) were 134.4 U/mL (95% CI: 104.5-172.9) and 163.7 U/mL (95% CI: 98.9-271.1).

Methods: Healthy infants aged 6-12 weeks, received two oral doses of either the RIX4414 vaccine stored at 2 °C-8 °C, RIX4414 vaccine stored at 37 °C for 7 days or placebo, according to a 0, 2 month schedule. Seroconversion rates in terms of anti-rotavirus IgA antibody levels (cut off: ≥ 20 U/mL by ELISA), anti-rotavirus IgA antibody GMCs and vaccine take were calculated 2 months post-Dose 2.

Conclusion: Lyophilized RIX4414 vaccine stored at 37°C for 7 days before reconstitution has similar immunogenicity as the vaccine stored at 2 °C-8 °C. These results supported the use of RIX4414 in settings where the vaccine might be exposed to higher than the recommended storage temperatures.

Trial registration: ClinicalTrials.gov NCT00169455.