Available online 12 November 2022, 105328

The booster mRNA vaccines induced significant higher titer and increased breadth of neutralizing antibodies against SARS-CoV-2 variants than that by protein vaccine.

Half-dose mRNA-1273 elicited less reactogenicity but induced a comparable immune response to full-dose mRNA-1273.

T cell response was equal in health care workers primed by the ChAdOx1 nCov-19 after mRNA or protein vaccine heterologous booster immunization.

Anti-spike antibody is highly correlated with neutralizing antibody.

: We conducted a single-blinded, randomized trial to evaluate the safety, reactogenicity, and immunogenicity of heterologous booster vaccination in health care workers (HCW) who had received two doses of ChAdOx1 nCov-19.

: HCW who had at least 90 days after the second dose were enrolled to receive one of the four vaccines: BNT162b2 (30 μg), half-dose mRNA-1273 (50 μg), mRNA-1273 (100 μg), and MVC-COV1901 (15 μg). The primary outcomes were humoral and cellular immunogenicity and secondary outcomes assessed safety and reactogenicity at 28 days post-booster.

: Three hundred and forty HCW were enrolled: 83 received BNT162b2 (2 excluded), 85 half-dose mRNA-1273, 85 mRNA-1273, and 85 MVC-COV1901. mRNA vaccines had more reactogenicity than protein vaccine. The fold-rise of anti-spike IgG geometric mean titer was 8.4 (95% CI 6.8-10.4) for MCV-COV1901, 32.2 (27.2-38.1) for BNT162b2, 47.6 (40.8-55.6) for half-dose mRNA-1273 and 63.2 (53.6-74.6) for mRNA-1273. The live virus microneutralization assays (LVMNA) against the wild type, alpha and delta variants were consistent with anti-spike IgG for all booster vaccines. The LVMNA in the four groups against omicron BA.1 variant were 6.4 to 13.5 times lower than those against the wild type. All booster vaccines induced a comparable T cell response.

: Third dose booster not only increases neutralizing antibody titer but also enhances antibody breadth against SARS-CoV-2 variants. mRNA vaccines are preferred booster vaccines for those who received primary series of ChAdOx1 nCov-19.

COVID-19

Vaccine

Heterologous booster

Third dose

Immunogenicity

Safety

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