The search for developing effective vaccines against SARS‐CoV‐2 began with the start of the COVID‐19 pandemic, and the first vaccine dose was administered in December 2020. Today, full vaccination of most of the world's population is considered the most important means to overcome the COVID‐19 pandemic. Vaccination has been associated with various struggles. Some adverse reactions have resulted in the discontinuation of the specific vaccines use in some countries. Countries in poor regions have faced difficulties supplying enough vaccine doses, and the emergence of new variants of concern has resulted in reduced effectiveness of available vaccines against COVID‐19. The mix‐and‐match strategy, using heterologous vaccines in the first and second doses, might successfully solve the mentioned struggles. Moreover, this strategy has been associated with higher cellular and humoral immune responses without significantly increasing the adverse reactions. Hence, this strategy can help improve the vaccines' effectiveness, and act as a solution for vaccine shortage in poor regions.

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Declaration of interests: The authors declare that they have no conflict of interests. Authors' contribution: All the authors had substantial contributions to the conception of the work. Drafting of the work was done by NS and NR; the remaining authors did critical revision. All approved the final draft and agree to be accountable for all aspects of the work.