Immunogenicity of a Third Scheduled Dose of Rotarix in Australian Indigenous Infants: A Phase IV, Double-blind, Randomized, Placebo-Controlled Clinical Trial

Bianca F Middleton, Margie Danchin, Mark A Jones, Amanda J Leach, Nigel Cunliffe, Carl D Kirkwood, Jonathan Carapetis, Sarah Gallagher, Lea-Ann Kirkham, Caitlyn Granland, Monica McNeal, Julie A Marsh, Claire S Waddington, Thomas L Snelling, Bianca F Middleton, Margie Danchin, Mark A Jones, Amanda J Leach, Nigel Cunliffe, Carl D Kirkwood, Jonathan Carapetis, Sarah Gallagher, Lea-Ann Kirkham, Caitlyn Granland, Monica McNeal, Julie A Marsh, Claire S Waddington, Thomas L Snelling

Abstract

Background: Rotarix (GlaxoSmithKline) oral rotavirus vaccine is licensed as 2 doses in the first 6 months of life. In settings with high child mortality rates, clinical protection conferred by 2 doses of Rotarix is reduced. We assessed vaccine immune response when an additional dose of Rotarix was given to Australian Aboriginal children 6 to <12 months old.

Methods: ORVAC is a 2-stage, double-blind, randomized, placebo-controlled trial. Australian Aboriginal children 6 to <12 months old who had received 1 or 2 prior doses of Rotarix rotavirus vaccine were randomized 1:1 to receive an additional dose of Rotarix or matched placebo. The primary immunological end point was seroresponse defined as an anti-rotavirus immunoglobulin A level ≥20 AU/mL, 28-56 days after the additional dose of Rotarix or placebo.

Results: Between March 2018 and August 2020, a total of 253 infants were enrolled. Of these, 178 infants (70%) had analyzable serological results after follow-up; 89 were randomized to receive Rotarix, and 89 to receive placebo. The proportion with seroresponse was 85% after Rotarix compared with 72% after placebo. There were no occurrences of intussusception or any serious adverse events.

Conclusions: An additional dose of Rotarix administered to Australian Aboriginal infants 6 to <12 months old increased the proportion with a vaccine seroresponse.

Clinical trials registration: NCT02941107.

Keywords: Aboriginal; Immunogenicity; Rotarix; clinical trial; rotavirus vaccine.

Conflict of interest statement

Potential conflict of interests. N. C. declares that his employer, the University of Liverpool, has received grant funding for rotavirus research from GlaxoSmithKline, the manufacturer of Rotarix. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Trial profile. Flow diagram shows the progress of participants through ORVAC stage 1.
Figure 2.
Figure 2.
Change in anti-rotavirus immunoglobulin A (IgA) titer from baseline to 28–56 days after the additional dose of Rotarix or placebo. Abbreviation: AU, arbitrary units.

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