Accepted 12 October 2021
Payne, R.P., Longet, S., Austin, J.A., Skelly, D.T., Dejnirattisai, W., Adele, S., Meardon, N., Faustini, S., Al-Taei, S., Moore, S.C., Tipton, T., Hering, L.M, Angyal, A., Brown, R., Nicols, A.R, Gillson, N., Dobson, S.L, Amini, A., Supasa, P., Cross, A., Bridges-Webb, A., Reyes, L.S., Linder, A., Sandhar, G., Kilby, J.A., Tyerman, J.K, Altmann, T., Hornsby, H., Whitham, R., Phillips, E., Malone, T., Hargreaves, A., Shields, A., Saei, A., Foulkes, S., Stafford, L., Johnson, S., Wootton, D.G., Conlon, C.P., Jeffery, K., Matthews, P.C., Frater, J., Deeks, A.S., Pollard, A.J., Brown, A., Rowland- Jones, S.L., Mongkolsapaya, J., Barnes, E., Hopkins, S., Hall, V., Dold, C., Duncan, C.J., Richter, A., Carroll, M., Screaton, G., de Silva, T.I., Turtle, L., Klenerman, P., Dunachie, S., on behalf of the PITCH Consortium, Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine,Cell (2021)
Highlights
•BNT162b2 vaccine with an extended interval between doses is highly protective
•Antibody levels were higher after the extended regimen compared to the short regimen
•The extended regimen enriches for virus-specific CD4+ T cells expressing IL-2
•Antibody levels wane after each dose but B and T cell pools are maintained
Summary
Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the UK to accelerate population coverage with a single dose. At this time, trial data was lacking, and we addressed this in a study of UK healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) variant over several weeks. In a sub-study of 589 individuals, we show that this single dose induces SARS-CoV-2 neutralizing antibody (NAb) responses and a sustained B and T cell response to spike protein. NAb levels were higher after the extended dosing interval (6-14 weeks) compared to the conventional 3-4 week regimen, accompanied by enrichment of CD4+ T cells expressing IL2. Prior SARS-CoV-2 infection amplified and accelerated the response. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective, immunogenic protocol.
