A Promising Vaccination Strategy against COVID-19 on the Horizon: Heterologous Immunization

J Microbiol Biotechnol. 2021 Dec 28;31(12):1601-1614. doi: 10.4014/jmb.2111.11026.


To overcome the ongoing COVID-19 pandemic, vaccination campaigns are the highest priority of majority of countries. Limited supply and worldwide disproportionate availability issues for the approved vaccines, together with concerns about rare side-effects have recently initiated the switch to heterologous vaccination, commonly known as mixing of vaccines. The COVID-19 vaccines are highly effective in the general population. However, none of the vaccines is 100% efficacious or effective, with variants posing more challenges, resulting in breakthrough cases. This review summarizes the current knowledge of immune responses to variants of concern (VOC) and breakthrough infections. Furthermore, we discuss the scope of heterologous vaccination and future strategies to tackle the COVID-19 pandemic, including fractionation of vaccine doses and alternative route of vaccination.

Keywords: SARS-CoV-2; heterologus vaccination; hybrid immunity; variants of concern.

Publication types

  • Review

MeSH terms

  • Animals
  • COVID-19 / immunology
  • COVID-19 / prevention & control*
  • COVID-19 Vaccines / classification
  • COVID-19 Vaccines / immunology*
  • Clinical Trials as Topic
  • Humans
  • Immunity, Heterologous*
  • Mice
  • SARS-CoV-2 / immunology*
  • Vaccination / methods*
  • Vaccination / trends*


  • COVID-19 Vaccines

Supplementary concepts

  • SARS-CoV-2 variants