Immune response and safety of heterologous ChAdOx1-nCoV-19/mRNA-1273 vaccination compared with homologous ChAdOx1-nCoV-19 or homologous mRNA-1273 vaccination

Abstract

Background/purpose: Efficacy and safety data of heterologous prime-boost vaccination against SARS-CoV-2 remains limited.

Methods: We recruited adult volunteers for homologous or heterologous prime-boost vaccinations with adenoviral (ChAdOx1, AstraZeneca) and/or mRNA (mRNA-1273, Moderna) vaccines. Four groups of prime-boost vaccination schedules were designed: Group 1, ChAdOx1/ChAdOx1 8 weeks apart; Group 2, ChAdOx1/mRNA-1273 8 weeks apart; Group 3, ChAdOx1/mRNA-1273 4 weeks apart; and Group 4, mRNA-1273/mRNA-1273 4 weeks apart. The primary outcome was serum anti-SARS-CoV-2 IgG titers and neutralizing antibody titers against B.1.1.7 (alpha) and B.1.617.2 (delta) variants on day 28 after the second dose. Adverse events were recorded up until 84 days after the second dose.

Results: We enrolled 399 participants with a median age of 41 years and 75% were female. On day 28 after the second dose, the anti-SARS-CoV-2 IgG titers of both heterologous vaccinations (Group 2 and Group 3) were significantly higher than that of homologous ChAdOx1 vaccination (Group 1), and comparable with homologous mRNA-1273 vaccination (Group 4). The heterologous vaccination group had better neutralizing antibody responses against the alpha and delta variant as compared to the homologous ChAdOx1 group. Most of the adverse events (AEs) were mild and transient. AEs were less frequent when heterologous boosting was done at 8 weeks rather than at 4 weeks.

Conclusion: Heterologous ChAdOx1/mRNA-1273 vaccination provided higher immunogenicity than homologous ChAdOx1 vaccination and comparable immunogenicity with the homologous mRNA-1273 vaccination. Our results support the safety and efficacy of heterologous prime-boost vaccination using the ChAdOx1 and mRNA-1273 COVID-19 vaccines. (ClinicalTrials.gov number, NCT05074368).

Keywords: Adenovirus-vector vaccine; Coronavirus disease 2019 (COVID-19); Immune response; Messenger RNA vaccine; Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2).

Figure 1

Classification of four study groups in this study.

Figure 2

SARS-CoV-2 anti-spike IgG responses and spike-specific memory B cell responses after boost dose among four groups. (A) Distributions of SARS-CoV-2 anti-spike IgG responses at the day before and 14th, 28th, and 84th days after boost vaccination; (B) Responses of spike-specific memory B cells at the day before and 28th days after boost dose among four groups. (∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.005, ∗∗∗∗P < 0.001).

Figure 3

The serum neutralizing antibody titers (NT₅₀) of 4 Groups of study subjects against SARS-CoV-2 (A) Alpha variant, and (B) Delta variant.

Figure 4

Immunological response of SARS-CoV-2 spike-specific memory T cells before and at 28th day post boost vaccination among four groups. Intracellular staining of cytokines in spike-specific CD8⁺ T cells (A) and spike-specific CD4⁺ T cells (B). (C) Th1/Th2 cytokine production by T cells using bead-based cytokine assay. (∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.005, ∗∗∗∗P < 0.001).