Third dose vaccination with mRNA-1273 or BNT162b2 vaccines improves protection against SARS-CoV-2 infection 

April 28 2022

As of November 29, 2021, booster vaccination against SARS-CoV-2 infection has been recommended for all individuals aged 18 years and older in the United States. A key reason for this recommendation is the expectation that a booster vaccine dose can alleviate observed waning of vaccine effectiveness. Although initial reports of booster effectiveness have been positive, the level of protection from booster vaccination is unclear. We conducted two studies to assess the impact of booster vaccination, with BNT162b2 or mRNA-1273, on the incidence of SARS-CoV-2 infection between August and December 2021. We first compared SARS-CoV-2 infection incidence in cohorts of 3-dose vaccine recipients to incidence in matched cohorts of 2-dose vaccine recipients (cohort size = 24,539 for BNT162b2 and 14,004 for mRNA-1273). Additionally, we applied a test-negative study design to compare the level of protection against symptomatic infection in 3-dose recipients to that observed in recent 2-dose primary vaccine series recipients. 3-dose recipients experienced a significantly lower incidence rate of SARS-CoV-2 infection than the matched 2-dose cohorts (BNT162b2 Incidence Rate Ratio: 0.11, 95% CI: 0.09–0.13 and mRNA-1273 IRR: 0.11, 95% CI: 0.08–0.15). Results from the test-negative study showed the third vaccine dose mitigated waning of vaccine effectiveness, with the risk of symptomatic infection in 3-dose recipients being comparable to that observed 7–73 days after the primary vaccine series. These results show that 3-dose vaccine regimens with BNT162b2 or mRNA-1273 are effective at reducing SARS-CoV-2 infection and support the widespread administration of booster vaccine doses.


Michiel J M Niesen, Robert Matson, Arjun Puranik, John C O'Horo, Colin Pawlowski, Celine Vachon, Douglas Challener, Abinash Virk, Melanie Swift, Leigh Speicher, Joel Gordon, Holly Geyer, Patrick J Lenehan, A J Venkatakrishnan, Venky Soundararajan, Andrew Badley

nference, Cambridge, MA 02142, USA Mayo Clinic, Rochester, MN 55905, USA

Mayo Clinic


Correspondence to:

Venky Soundararajan (