Immunogenicity and Reactogenicity of BNT162b2 and mRNA1273 COVID-19 Vaccines Given as Fourth Dose Boosters in the COV-BOOST Randomised Trial Following Two Doses of ChAdOx1 nCov-19 or BNT162b2 and a Third Dose of BNT162b2 (preprint)

ABSTRACT

Background: Many high-income countries have deployed third “booster” doses of COVID-19 vaccines to populations and some countries have started offering fourth doses. Methods: The COV-BOOST trial is a multicentre, randomised, controlled, phase II trial of seven COVID-19 vaccines as third dose boosters. The current study invited participants who received BNT162b2 (BNT) as third dose in COV-BOOST to be randomised to receive a fourth dose of BNT or mRNA1273 (50 µg, half-m1273). The COV-BOOST trial is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. Results: Between 11 and 25 January 2022, 166 participants in the original BNT arm were randomised and received a fourth dose vaccine. The median age was 70.1 (interquartile range 51.6-77.5) years with 51.8 % (n=86) female participants. The median interval between third and fourth dose was 208.5 (interquartile range 203.25-214.75) days.Pain and fatigue were the most common local and systemic solicited adverse events for BNT and half-m1273. None of three serious adverse events reported after a fourth dose were related to study vaccine.The fold rises in anti-spike IgG pre- and post-fourth dose were 12.19 (95%CI 10.37-14.32) and 15.90 (95%CI 12.92-19.58) in BNT and half-m1273 arms respectively, with fold changes compared to the post third dose-peak of 1.59 (95%CI 1.41-1.78) and 2.19 (95%CI 1.90-2.52). T cell responses also boosted. Conclusions: Fourth dose COVID-19 mRNA booster vaccines are well-tolerated and boost cellular and humoral immunity up to, and beyond peak levels achieved following third dose boosters (ISRCTN 73765130).