BACKGROUND AND PURPOSE:

• Hillus et al. (The Lancet Respiratory Medicine, 2021) assessed the reactogenicity and immunogenicity of heterologous administration of the AstraZeneca and Pfizer vaccines, compared with homologous immunization

METHODS:

• Interim analysis of prospective observational cohort study data
• Participants
  • Healthcare workers in Berlin
  • Enrolled between Dec 2020 and Jun 2021
• Exposures
  • Homologous (Hom) AstraZeneca vaccination, with a 10-to-12-week interval
  • Homologous (Hom) Pfizer vaccination, with a 3-week vaccine interval
  • Heterologous (Het) AstraZeneca-Pfizer vaccination, with a 10-to-12-week interval
• Study design
  • Reactogenicity was examined after the first and second dose via electronic questionnaires on days 1, 3, 5, and 7 following immunization
  • Immunogenicity was measured by
    • The presence of SARS-CoV-2-specific antibodies (full spike-IgG, S1-IgG, and RBD-IgG)
    • An RBD–ACE2 binding inhibition assay (virus neutralization test)
    • A pseudovirus neutralization assay against two variants of concerns (alpha [B.1.1.7] and beta [B.1.351])
    • Anti-S1-IgG avidity
  • T-cell reactivity was measured by IFN-γ release assay

RESULTS:

• Homologous Pfizer: 174 | Homologous AstraZeneca: 38 | Heterologous: 104
• Participants experiencing systemic symptoms following the second dose
  • Hom Pfizer: 65% (95% CI, 57.1 to 71.8)
  • Hom AstraZeneca: 39% (95% CI, 24.8 to 55.1)
  • Het: 49% (95% CI, 39.6 to 58.5)
• Median anti-RBD IgG levels 3 weeks after second dose
  • Hom Pfizer: 5.4 signal to cutoff ratio (S/co) (IQR 4.8 to 5.9)
  • Hom AstraZeneca: 4.9 S/co (IQR 4.3 to 5.6)
  • Het: 5.6 S/co (IQR 5.1 to 6.1)
• Geometric mean of 50% inhibitory dose against alpha and beta variants were highest in participants with the heterologous vaccine regimen, compared to both other vaccine regimens (P<0.0001)
  • Heterologous
    • Against alpha: 956.6 (95% CI, 835.6 to 1095)
    • Against beta: 417.1 (95% CI, 349.3 to 498.2)
  • Homologous Pfizer
    • Against alpha: 369.2 (95% CI, 310.7 to 438.6)
    • Against beta: 72.4 (95% CI, 60.5 to 86.5)
  • Homologous AstraZeneca:
    • Against alpha: 212.5 (95% CI, 131.2 to 344.4)
    • Against beta: 48.5 (95% CI, 28.4 to 82.8)
• SARS-CoV-2 S1 T-cell reactivity 3 weeks after second dose was highest in the participants with the heterologous vaccine regimen, compared to both other vaccine regimens
  • Heterologous
    • Median IFN-γ concentration 4762 mIU/mL (IQR 2723 to 8403)
  • Homologous Pfizer (P<0.0001)
    • Median IFN-γ concentration 1061 mIU/mL (IQR 599 to 2274)
  • Homologous AstraZeneca (P=0.0008)
    • Median IFN-γ concentration 2026 mIU/mL (IWR 1459 to 4621)

CONCLUSION:

• Heterologous vaccine administration of AstraZeneca followed 10 to 12 weeks later with a dose of Pfizer, was as well tolerated as the homologous administration regimens and demonstrated improved immunogenicity vs homologous regimen of AstraZeneca or Pfizer
• The authors conclude

In light of increasing occurrence of new virus variants carrying immune escape mutations, it will be important to determine vaccine efficacy of heterologous vaccination regimens, particularly regarding protection against severe COVID-19

Our data support further studies into the applicability of heterologous prime-boost vaccination strategies for COVID-19

Learn More – Primary Sources:

Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1 nCoV-19 and BNT162b2: a prospective cohort study

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AstraZeneca First Dose and mRNA Second Dose: How Does the ‘Mix & Match’ Immune Response Stack Up?

mRNA-Based COVID-19 Vaccines Induce Robust, Persistent Immune Responses in Humans

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