Vaccines are the most successful instruments in the prevention of infectious diseases and are considered a solution to the ongoing SARS-CoV-2 pandemic. Vaccines against COVID-19 have been developed at an unprecedented speed, and several vaccines have already been approved and deployed globally. COVID-19 vaccines have been shown to be safe, however serious side-effects have also been reported, and more time is needed to assess the potential long-term adverse effects. Current COVID-19 vaccines can protect from the development of severe disease, typified by pneumonia, cytokine storm, acute respiratory distress syndrome (ARDS), multiorgan failure, and death. However, these vaccines do not appear to completely prevent SARS-CoV-2 infection, and may be ineffective against the emerging novel SARS-CoV-2 variants capable of evading the immunity in vaccinated individuals. The reason for this may be due to the failure of most COVID-19 vaccines in inducing long-term immunological memory. While we have learned a lot in a short period of time, it is time to strategize new thinking in the development of more durable COVID-19 vaccines, capable of inducing long-term protection against the emerging variants.

Unless we can develop a COVID-19 vaccine that can provide long-term sterilizing immunity, SARS-CoV-2 infections will likely become seasonal and require yearly immunizations, as is the case for influenza. To develop such a vaccine, we would need to consider the mechanism of interaction of the virus with the host, and the host’s response to the vaccine. Components of the innate immune system, such as monocytes, macrophages, dendritic cells, granulocytes, and other immune cell types demand greater attention. Moreover, vaccines can induce alternative activation of immune subsets, leading to a vaccine-induced protective immune response, which needs to be studied further and better understood. SARS-CoV-2 presents a slight difference in its infection pattern, which depends on multiple factors, such as age, sex, medical status, past infections with other coronaviruses, co-morbidities, and host genetics. This needs to be understood in detail to define the universal efficacy of SARS-CoV-2 vaccines. This Research Topic offers a window of opportunity for coalescing this much-needed information, which will be instrumental to the development of more durable COVID-19 vaccines in the future.

We welcome the submission of Original Research articles, Reviews, Mini-Reviews, Perspective articles, Opinion articles, and Commentaries around the following topics, which include but are not limited to:

• Identification of innate immune responses that correlate to protection.
• Elucidating the roles of major innate immune subset responses, which correlate to vaccine efficacy.
• Innate immune responses during SARS-CoV-2 vaccination, including DCs-mediated antigen presentation, macrophage-mediated response, granulocytes response, and others.
• Factors that affect the functions of innate immune cells during SARS-CoV-2 vaccination.
• Innate immune responses observed with endemic coronaviruses and in SARS-CoV-2 infected subjects or vaccinated individuals.

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Frontiers in Immunology

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