Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

• DOI: 10.1016/j.cell.2021.10.011
• Publication Date: 2021-10-18T21:37:25Z
• Authors: Rebecca P. Payne; Stephanie Longet; James A. Austin; Donal T. Skelly; Wanwisa Dejniratt...; Sandra Adele; Naomi Meardon; Sian Faustini; Saly Al-Taei; Shona C. Moore; Tom Tipton; Luisa M. Hering; Adrienn Angyal; Rebecca Brown; Alexander R. Nicols; Natalie Gillson; Susan L. Dobson; Ali Amini; Piyada Supasa; Andrew Cross; Alice Bridges-Webb; Laura Silva Reyes; Aline Linder; Gurjinder Sandhar; Jonathan A. Kilby; Jessica K. Tyerman; Thomas Altmann; Hailey Hornsby; Rachel Whitham; Eloise Phillips; Tom Malone; Alexander Hargreaves; Adrian Shields; Ayoub Saei; Sarah Foulkes; Lizzie Stafford; Sile Johnson; Daniel G. Wootton; Christopher P. Co...; Katie Jeffery; Philippa C. Matthews; John Frater; Alexandra S. Deeks; Andrew J. Pollard; Anthony Brown; Sarah L. Rowland-...; Juthathip Mongkol...; Eleanor Barnes; Susan Hopkins; Victoria Hall; Christina Dold; Christopher J.A. ...; Alex Richter; Miles Carroll; Gavin Screaton; Thushan I. de Silva; Lance Turtle; Paul Klenerman; Susanna Dunachie; Hibatullah Abuelg...; Emily Adland; Syed Adlou; Hossain Delowar A...; Ahmed Alhussni; Mohammad Ali; M. Azim Ansari; Carolina V. Aranc...; Martin Bayley; Helen Brown; Jeremy Chalk; Meera Chand; Anu Chawla; Senthil Chinnakannan; Joseph Cutteridge; Catherine de Lara; Lucy Denly; Ben Diffey; Stavros Dimitriadis; Thomas M. Drake; Timothy Donnison; Maeva Dupont; David Eyre; Alex Fairman; Siobhan Gardiner; Javier Gilbert-Ja...; Philip Goulder; Carl-Philipp Hack...; Sophie Hambleton; Muzlifah Haniffa; Jenny Haworth; Jennifer Holmes; Emily Horner; Anni Jämsén; Sile Johnson; Chris Jones; Mwila Kasanyinga; Sinead Kelly; Rosemary Kirk; Michael L. Knight; Allan Lawrie; Lian Lee; Lauren Lett; Katy Lillie; Nicholas Lim; Hema Mehta; Alexander J. Mentzer; Denise O’Donnell; Ane Ogbe; Matthew Pace; Brendan A.I. Payne; Gareth Platt; Sonia Poolan; Nicholas Provine; Narayan Ramamurthy; Nichola Robinson; Leigh Romaniuk; Patpong Rongkard; Oliver L. Sampson; Beatrice Simmons; Jarmila S. Spegarova; Emily Stephenson; Kris Subramaniam; James Thaventhiran; Sarah Thomas; Simon Travis; Stephanie Tucker; Helena Turton; Adam Watson; Lisa Watson; Esme Weeks; Robert Wilson; Steven Wood; Rachel Wright; Huiyuan Xiao; Amira A.T. Zawia
• Keywords: Adult; Male; COVID-19 Vaccines; T-Lymphocytes; Dose-Response Relationship, Immunologic; 610; Antibodies, Viral; Article; 03 medical and health sciences; Cross-Priming; Ethnicity; Humans; BNT162 Vaccine; Aged; 0303 health sciences; SARS-CoV-2; Immunity; COVID-19; Middle Aged; Reference Standards; Antibodies, Neutralizing; 3. Good health; Immunoglobulin G; Linear Models; Female

Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the United Kingdom to accelerate population coverage with a single dose. At this time, trial data were lacking, and we addressed this in a study of United Kingdom healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) variant over several weeks. In a substudy of 589 individuals, we show that this single dose induces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) responses and a sustained B and T cell response to the spike protein. NAb levels were higher after the extended dosing interval (6-14 weeks) compared with the conventional 3- to 4-week regimen, accompanied by enrichment of CD4+ T cells expressing interleukin-2 (IL-2). 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.