To mix or not to mix? A rapid systematic review of heterologous prime-boost covid-19 vaccination

Expert Rev Vaccines. 2021 Oct;20(10):1211-1220. doi: 10.1080/14760584.2021.1971522. Epub 2021 Sep 1.


Introduction: Coronavirus disease 2019 (COVID-19) has had an enormous impact worldwide, and vaccination is believed to be the method that will control the pandemic. Several types of vaccines developed using different platforms have been authorized, but the immunogenicity and reactogenicity of heterologous prime-boost vaccination with different vaccines remain largely unclear.

Areas covered: Electronic databases including PubMed, Embase, medRxiv, Research Square, and SSRN were searched to investigate the immunogenicity and reactogenicity associated with heterologous vaccination.As of 30 June 2021, four trials including 1,862 participants were identified. Heterologous administration of BNT162b2 (BNT) in ChAdOx1 (ChAd)-primed participants (ChAd/BNT) showed noninferior immunogenicity to homologous BNT administration (both prime and booster were BNT vaccines, BNT/BNT) with tolerable reactogenicity and higher T cell responses. Compared with homologous ChAdOX1 vaccination (ChAd/ChAd), heterologous ChAd/BNT was found to elicit higher immunogenicity (ChAd/BNT vs. ChAd/ChAd, antibody titer ratio: 9.2).

Expert opinion: Our systematic review found robust immunogenicity and tolerable reactogenicity of heterologous administration of a BNT162b2 boost in ChAdOx1-primed participants. An additional benefit of stronger T cellular immunity was also observed. Heterologous vaccination is a reasonable and feasible strategy to combat COVID-19. Further studies are warranted to confirm the benefits and identify the optimal combinations, doses, and intervals.

Keywords: BNT162B2; COVID-19; Sars-COV-2; boost; chadox1; heterologous; mRNA; vaccination.

Publication types

  • Systematic Review

MeSH terms

  • BNT162 Vaccine
  • COVID-19 / immunology
  • COVID-19 / prevention & control*
  • COVID-19 / virology
  • COVID-19 Vaccines / administration & dosage*
  • COVID-19 Vaccines / immunology
  • Humans
  • Immunogenicity, Vaccine
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / isolation & purification
  • Vaccination


  • COVID-19 Vaccines
  • BNT162 Vaccine

Supplementary concepts

  • heterologous prime boost COVID-19 vaccination

Grants and funding

This research received no external funding.