Are All COVID-19 Vaccine Booster Options Created Equal?

Despite the remarkably durable protection that COVID-19 vaccines provide against severe disease, their effectiveness against SARS-CoV-2 infection eventually wanes. In a study to inform decisions about boosting, U.K. investigators randomized 2878 participants aged ≥30 who had previously received 2 doses of ChAdOx1 nCoV-19 (ChAd; Oxford-AstraZeneca) or BNT162b2 (BNT; Pfizer-BioNTech) to receive one of the following as a third dose:

• Meningococcal vaccine (control)

• NVX-CoV2373 (Novavax; full or half dose)

• ChAd

• BNT (full or half dose)

• VLA2001 (whole inactivated virus with adjuvant [Valneva]; full or half dose)

• Ad26.COV2.S (Johnson & Johnson)

• mRNA1273 (Moderna)

• CVnCov (CureVac, novel mRNA vaccine)

Fatigue, headache, and pain were the most common reactions (more so among younger participants). In participants primed with ChAd/ChAd, anti-S geometric mean ratios (GMR) for vaccine compared with control were lowest for half-dose VLA2001 (1.8) and highest for mRNA1273 (32.3). Cellular responses were not augmented after boosting with ChAd or VLA2001 and were highest following mRNA1273 boost (GMR, 3.6). In participants primed with BNT/BNT, GMR for vaccine compared with control were lowest for half-dose VLA2001 (1.3) and highest for mRNA1273 (11.5). Cellular responses were not augmented after boosting with half-dose NVX and were highest following mRNA1273 boost (GMR, 4.7). Neutralizing antibody responses mirrored binding antibody responses.