| Summary: | The most important characteristics regarding the mucosal infection and immune responses against the Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) as well as the current vaccines against coronavirus disease 2019 (COVID-19) in development or use are revised to emphasize the opportunity for lactic acid bacteria (LAB)-based vaccines to offer a valid alternative in the fight against this disease. In addition, this article revises the knowledge on: (a) the cellular and molecular mechanisms involved in the improvement of mucosal antiviral defenses by beneficial <i>Lactiplantibacillus plantarum</i> strains, (b) the systems for the expression of heterologous proteins in <i>L. plantarum</i> and (c) the successful expressions of viral antigens in <i>L. plantarum</i> that were capable of inducing protective immune responses in the gut and the respiratory tract after their oral administration. The ability of <i>L. plantarum</i> to express viral antigens, including the spike protein of SARS-CoV-2 and its capacity to differentially modulate the innate and adaptive immune responses in both the intestinal and respiratory mucosa after its oral administration, indicates the potential of this LAB to be used in the development of a mucosal COVID-19 vaccine.
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