Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses
Barrett JR., Belij-Rammerstorfer S., Dold C., Ewer KJ., Folegatti PM., Gilbride C., Halkerston R., Hill J., Jenkin D., Stockdale L., Verheul MK., Aley PK., Angus B., Bellamy D., Berrie E., Bibi S., Bittaye M., Carroll MW., Cavell B., Clutterbuck EA., Edwards N., Flaxman A., Fuskova M., Gorringe A., Hallis B., Kerridge S., Lawrie AM., Linder A., Liu X., Madhavan M., Makinson R., Mellors J., Minassian A., Moore M., Mujadidi Y., Plested E., Poulton I., Ramasamy MN., Robinson H., Rollier CS., Song R., Snape MD., Tarrant R., Taylor S., Thomas KM., Voysey M., Watson MEE., Wright D., Douglas AD., Green CM., Hill AVS., Lambe T., Gilbert S., Pollard AJ., Oxford CVTG.
More than 190 vaccines are currently in development to prevent infection by the novel severe acute respiratory syndrome coronavirus 2. Animal studies suggest that while neutralizing antibodies against the viral spike protein may correlate with protection, additional antibody functions may also be important in preventing infection. Previously, we reported early immunogenicity and safety outcomes of a viral vector coronavirus vaccine, ChAdOx1 nCoV-19 (AZD1222), in a single-blinded phase 1/2 randomized controlled trial of healthy adults aged 18-55 years ( NCT04324606 ). Now we describe safety and exploratory humoral and cellular immunogenicity of the vaccine, from subgroups of volunteers in that trial, who were subsequently allocated to receive a homologous full-dose (SD/SD D56; n = 20) or half-dose (SD/LD D56; n = 32) ChAdOx1 booster vaccine 56 d following prime vaccination. Previously reported immunogenicity data from the open-label 28-d interval prime-boost group (SD/SD D28; n = 10) are also presented to facilitate comparison. Additionally, we describe volunteers boosted with the comparator vaccine (MenACWY; n = 10). In this interim report, we demonstrate that a booster dose of ChAdOx1 nCoV-19 is safe and better tolerated than priming doses. Using a systems serology approach we also demonstrate that anti-spike neutralizing antibody titers, as well as Fc-mediated functional antibody responses, including antibody-dependent neutrophil/monocyte phagocytosis, complement activation and natural killer cell activation, are substantially enhanced by a booster dose of vaccine. A booster dose of vaccine induced stronger antibody responses than a dose-sparing half-dose boost, although the magnitude of T cell responses did not increase with either boost dose. These data support the two-dose vaccine regime that is now being evaluated in phase 3 clinical trials.