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Developed countries have ample supplies of various vaccines against SARS-CoV-2 — but the question of which vaccination strategy yields the best immune response remains unanswered. Two studies add pieces to this puzzle.
Normark et al. assessed SARS-CoV-2–specific immune responses in 88 healthcare workers who had received the ChAdOx1 (Oxford/AstraZeneca) vaccine; 9 to 12 weeks later, 51 opted to receive a booster with mRNA-1273 (Moderna; heterologous boost) and 37 chose to receive another ChAdOx1 dose (homologous boost). At boost, levels of SARS-CoV-2 spike-specific and receptor-binding domain (RBD) −specific IgG and neutralizing antibodies were similar between groups; 7 to 10 days later, antibody levels were 5 times higher in ChAdOx1 boost recipients and 115 to 125 times higher in mRNA-1273 recipients. At 7 to 10 days, neutralization titers against wild-type virus were doubled (homologous boost) and 20-fold higher (heterologous boost) compared with day of boost, rising further in both groups by day 30. Sera from heterologous-boosted but not homologous-boosted individuals neutralized the SARS-CoV-2 Beta variant (B.1.351).
Barouch et al. evaluated humoral and cellular immune responses in 20 subjects within 8 months of vaccination with the Ad26.COV2.S (Johnson & Johnson) vaccine. Anti-RBD and virus neutralizing titers peaked at day 71. All participants showed durable spike-specific CD8+ and CD4+ T-cell responses. Antibody levels against SARS-CoV-2 variants appeared to develop over the 8-month period, gaining neutralizing capacity against all prevalent variants.
Normark J et al. Heterologous ChAdOx1 nCoV-19 and mRNA-1273 vaccination. N Engl J Med 2021 Jul 14; [e-pub]. (https://doi.org/10.1056/NEJMc2110716)
Barouch DH et al. Durable humoral and cellular immune responses after Ad26.COV2.S vaccination. N Engl J Med 2021 Jul 14; [e-pub]. (https://doi.org/10.1056/NEJMc2108829)
Comment
The robust antibody responses after heterologous prime-boost vaccination with ChAdOx1 and mRNA-1273 aren't surprising, as phase III vaccine trials have already demonstrated significantly higher neutralizing antibody titers in mRNA-vaccine recipients (NEJM JW Infect Dis Jul 2021 and Nat Med 2021 May 17; [e-pub]), and coverage of variants also seems broader. Therefore, an mRNA-vaccine booster can be recommended for individuals who previously received one dose of a vector-based vaccine (including Ad26.COV2.S, even though immune responses to this vaccine appear to mature over time). However, it remains unclear whether heterologous vaccination is generally superior to the two-dose mRNA vaccine regimen.