Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

Payne, Rebecca P.; Longet, Stephanie; Austin, James A.; Skelly, Donal T.; Dejnirattisai, Wanwisa; Adele, Sandra; Meardon, Naomi; Faustini, Sian; Al-Taei, Saly; Moore, Shona C.; Tipton, Tom; Hering, Luisa M.; Angyal, Adrienn; Brown, Rebecca; Nicols, Alexander R.; Gillson, Natalie; Dobson, Susan L.; Amini, Ali; Supasa, Piyada; Cross, Andrew; Bridges-Webb, Alice; Reyes, Laura Silva; Linder, Aline; Sandhar, Gurjinder; Kilby, Jonathan A.; Tyerman, Jessica K.; Altmann, Thomas; Hornsby, Hailey; Whitham, Rachel; Phillips, Eloise; Malone, Tom; Hargreaves, Alexander; Shields, Adrian; Saei, Ayoub; Foulkes, Sarah; Stafford, Lizzie; Johnson, Sile; Wootton, Daniel G.; Conlon, Christopher P.; Jeffery, Katie; Matthews, Philippa C.; Frater, John; Deeks, Alexandra S.; Pollard, Andrew J.; Brown, Anthony; Rowland-Jones, Sarah L.; Mongkolsapaya, Juthathip; Barnes, Eleanor; Hopkins, Susan; Hall, Victoria; Dold, Christina; Duncan, Christopher JA.; Richter, Alex; Carroll, Miles; Screaton, Gavin; de Silva, Thushan I.; Turtle, Lance; Klenerman, Paul; Dunachie, Susanna

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.