Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine
Payne RP., Longet S., Austin JA., Skelly DT., Dejnirattisai W., Adele S., Meardon N., Faustini S., Al-Taei S., Moore SC., Tipton T., Hering LM., Angyal A., Brown R., Nicols AR., Gillson N., Dobson SL., Amini A., Supasa P., Cross A., Bridges-Webb A., Reyes LS., Linder A., Sandhar G., Kilby JA., Tyerman JK., Altmann T., Hornsby H., Whitham R., Phillips E., Malone T., Hargreaves A., Shields A., Saei A., Foulkes S., Stafford L., Johnson S., Wootton DG., Conlon CP., Jeffery K., Matthews PC., Frater J., Deeks AS., Pollard AJ., Brown A., Rowland-Jones SL., Mongkolsapaya J., Barnes E., Hopkins S., Hall V., Dold C., Duncan CJA., Richter A., Carroll M., Screaton G., de Silva TI., Turtle L., Klenerman P., Dunachie S., PITCH Consortium None.
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. After giving a primary dose, delaying administration of a second dose of BNT162b2 COVID-19 vaccine up to 6-14 weeks continues to provide strong protection and contributes to favorable antibody, B cell, and T cell responses.