Guardians of the oral and nasopharyngeal galaxy: IgA and protection against SARS-CoV-2 infection

Abstract

In early 2020, a global emergency was upon us in the form of the coronavirus disease 2019 (COVID-19) pandemic. While horrific in its health, social and economic devastation, one silver lining to this crisis has been a rapid mobilization of cross-institute, and even cross-country teams that shared common goals of learning as much as we could as quickly as possible about the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and how the immune system would respond to both the virus and COVID-19 vaccines. Many of these teams were formed by women who quickly realized that the classical model of "publish first at all costs" was maladaptive for the circumstances and needed to be supplanted by a more collaborative solution-focused approach. This review is an example of a collaboration that unfolded in separate countries, first Canada and the United States, and then also Israel. Not only did the collaboration allow us to cross-validate our results using different hands/techniques/samples, but it also took advantage of different vaccine types and schedules that were rolled out in our respective home countries. The result of this collaboration was a new understanding of how mucosal immunity to SARS-CoV-2 infection vs COVID-19 vaccination can be measured using saliva as a biofluid, what types of vaccines are best able to induce (limited) mucosal immunity, and what are potential correlates of protection against breakthrough infection. In this review, we will share what we have learned about the mucosal immune response to SARS-CoV-2 and to COVID-19 vaccines and provide a perspective on what may be required for next-generation pan-sarbecoronavirus vaccine approaches.

Keywords: COVID-19; IgA; SARS-CoV-2; antibodies; gut; immune response; immunization; immunology; infection; mucosal immunity; saliva; spike; vaccination.

FIGURE 1

The castle and moat metaphor illustrates key differences between protective mucosal and systemic antibody responses

FIGURE 2

Not having local mucosal antibodies at the site of infection (upper airway) may put people at risk for infection, thus amplifying onward transmission. Correlates of protection allow us to predict protective responses without waiting to see the outcome of exposure to infection. Upper right, virion with protein and RNA components. Bottom right, antibodies bound to viral proteins. Left, an illustration of correlates of protection from disease (neutralizing IgG antibodies), and correlates of protection from infection (neutralizing IgA antibodies)