Coronaviruses are among the largest RNA viruses and genomes vary ~ 26–31 kB. pneumoniae is pleomorphic, cell wall-less, and among the smallest of bacteria. Mycoplasma pneumoniae as the Non-viral Model for COVID-19 Vaccinology? It is thereafter hypothesized that lactogenic immunity will model key immune responses that should be sought after vaccination or natural infection. The potential contributions of mucosal immunology and the adaptive maternal immune response are discussed as a prelude to how SARS-CoV-2-related immunity can be better understood. A selection of these insights are highlighted herein. Yet, the immune response after natural infection provides considerable insight that should be considered before vaccines are produced and trialed. Vaccines are often assessed through simplified vaccination and challenge (experimental or natural infection) protocols. There is considerable science that reflects on many issues of relevant immune responses in both coronavirology and other infection models. Nevertheless, remaining fundamental issues are whether an effective timely vaccine can be produced and whether safety acceptability is met. The speed of progression and the inherent desire to succeed have raised some controversy. The magnitude of the COVID-19 pandemic has pushed the scientific community towards expeditiously creating novel vaccines, and many have progressed through various stages of development. This review provides key insights that drive hypotheses into how the instinct of immunity and the intelligence of the maternal component of the common mucosal immune system has already guided us and may continue to do so effectively into a bright and safe future. In understanding both passive immunity and protection, the body is already primed to educate us with decisions of what constitutes protection and harm. Focus on common mucosal immunity can be underrated, and equally or more, focus on lactogenic immunity may be underestimated. Regardless of safeguards or promises that may be understood from laboratory or vertebrate experiments, observations from large-scale human trials will ultimately prove to shape the medical future. Many approaches to vaccination have emerged, and there may be more than one vaccine that will be applied, but individualized obstacles and concerns for administration, efficacy, and safety are inevitable. Whether for passive therapeutic strategies or vaccination, these findings provide a template for COVID-19. Animal model and human post-infection studies for SARS-CoV and MERS-CoV are largely corroborative. Animal coronavirus research has emphasized the importance of local mucosal protection (especially IgA) and systemic responses. Considerable study of endemic human coronaviruses has shown that neutralizing antibody correlates with protection, but effective clinical protection is variable for subsequent virus exposure. New data specific to COVID-19 are emerging quickly on key issues of immunity and prevention, but past research in coronavirology and for other human pathogens (e.g., Mycoplasma pneumoniae) has been available and of great relevance.
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