A single-blind, randomised, phase II multi-centre study to determine reactogenicity and immunogenicity of heterologous prime/boost COVID-19 vaccine schedules in adolescents (COMCOV-3)

The successful roll-out of COVID vaccines such as COVID-19 mRNA Vaccine BNT162b2 and the Oxford/AstraZeneca ChAdOx1 nCOV-19 vaccine has saved approximately 60 000 lives in the UK alone up to July 2021. Both of these vaccines are administered as a two-dose regimen, as is the adjuvanted protein COVID-19 vaccine from Novavax, NVXCoV2373, which is under rolling review of the MHRA at the time of writing. The use of heterologous prime/boost (mix and match) schedules of COVID-19 vaccines has already been studied in COMCOV and COMCOV2, and a schedule with ChAdOx1 nCOV-19 as the first dose, followed by BNT162b2 as the second dose has been shown to be highly immunogenic and is now deployed routinely in non-elderly populations in Canada and many northern European countries. Use of heterologous prime/boost schedules could also potentially be of benefit in an adolescent immunisation campaign. The potential benefits (and costs) of extending the UK COVID-19 vaccine immunisation to adolescents in the UK is under active review by the JCVI, and on 4th August 2021 it was announced that a first dose of BNT162b2 was recommended for all 16 to 17-year olds in the UK, with decisions about the timing and nature of the second dose to be decided. One concern regarding adolescent immunisation is a rare side effect of inflammation of the heart muscle (myocarditis) or lining of the heart (pericarditis) that has been observed after the second dose of BNT162b2, especially in young men. Mixed schedules with alternative vaccines used for the second dose, or using half doses of COVID-19 vaccines, could be an alternative that allows protection against COVID-19 while avoiding a second full dose of BNT162b2, and could also help deploy existing stocks of vaccine as effectively as possible. Accordingly, this study will determine the side effect profile, and the immune responses, following schedules using BNT162b2 as a first dose, and a second dose administered 8 weeks later of either BNT162b2 (full or half dose) or NVXCoV2373 (full dose) or an alternative mRNA produced by Moderna (half dose).