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 pansarbecoronavirus vaccine approaches.

Combined monitoring of IgG and IgA anti-Spike and anti-Receptor binding domain long term responses following BNT162b2 mRNA vaccination in Greek healthcare workers

“…Serum IgA Ab levels represents a useful biomarker reflecting the development of humoral immunity correlated with neutralizing activity in secretions at the mucosal surface [ 31 ]. Indeed, as also reviewed by Sheikh-Mohamed et al .”, mRNA vaccination (e.g., BNT162b2) leads to the development of robust RBD-specific Abs with neutralizing ability in the saliva, while the specific IgG and IgA levels exhibit similar dynamics to those, we observed in the sera of our cohort [ 34 ]. However, delayed Ab responses are more evident for the IgA anti-SARS-CoV-2 Abs generated by vaccination when compared to infection alone [ 20 , 35 , 36 ], supporting the need of the second vaccine dose in order to achieve efficient mucosal protection [ 15 , 37 , 38 ].…”

Two-Year Follow-Up on Chemosensory Dysfunction and Adaptive Immune Response after Infection with SARS-CoV-2 in a Cohort of 44 Healthcare Workers

“…A possible explanation for this correlation is that a lack of mucosal immune response leads to chronic inflammation of olfactory tissue and consequently to PCD [ 46 , 50 ]. This would imply that the mucosal immune response is a key regulator of SARS-CoV-2-induced chemosensory dysfunction, whereas systemic immunity plays a minor role [ 51 , 52 , 53 ]. This thesis is supported by studies showing no significant difference in the prevalence of chemosensory dysfunction during reinfection between patients with or without vaccination [ 5 , 54 ], whereas chemosensory dysfunction was less likely during reinfection in participants who had previously contracted SARS-CoV-2 [ 54 ].…”

“…This thesis is supported by studies showing no significant difference in the prevalence of chemosensory dysfunction during reinfection between patients with or without vaccination [ 5 , 54 ], whereas chemosensory dysfunction was less likely during reinfection in participants who had previously contracted SARS-CoV-2 [ 54 ]. In contrast to natural infection, most currently available SARS-CoV-2 vaccines generate only a limited mucosal immune response [ 52 , 55 ]. In our cohort, 20 of 44 (25.5%) participants were reinfected with SARS-CoV-2.…”

Differential Homing Receptor Profiles of Lymphocytes Induced by Attenuated versus Live Plasmodium falciparum Sporozoites

“…While these vaccines had a dramatic impact on morbidity and mortality caused by the virus, they are much less effective at preventing infection, especially infection with emerging viral variants, and transmission. The induction of protective mucosal immunity, presumably required for protection against infection and transmission, by SARS-CoV-2 vaccines (mRNA and Adenovirus-vectored) detected in saliva 2–4 weeks post-vaccination was transient and significantly reduced after 3 months [ 52 ]. Vaccines delivered via the intramuscular or subcutaneous route may induce only weak and transient mucosal immunity with few exemptions such as live-attenuated vaccines including the measles vaccine that induces a strong mucosal response in the upper and lower airway after parenteral delivery (s.c.) [ 53 ].…”