Mucosal Immunity and Novel Prophylactic Strategy to Combat COVID-19

The study aims to explore the role of mucosal immunity in combating COVID-19 with the objective of developing novel prophylactic and therapeutic strategies. Coronavirus disease 2019 (COVID-19) emerged as an expeditiously growing pandemic, in the human population caused by the highly transmissible RNA virus severe acute respiratory syndrome of coronavirus 2 (SARS-CoV-2). In clinical settings, SARS-CoV-2 infection can be elucidated on the basis of amplification of viral RNA from nasopharyngeal swab samples, and saliva tests (less invasive in nature), but sometimes faeces tests show the presence of SARS-CoV-2 RNA even prior to symptoms appear and also long after a patient has tested negative from a conventional swab. The interplay of SARS-CoV-2 infection predominantly occurs at the angiotensin-converting enzyme 2 receptor and transmembrane protease serine-type 2 positive (ACE2 + TMPRSS2+) epithelial cells of the mucosal surfaces like nasal, oral mucosae, and/or the conjunctival surface of the eye where it interacts with the immune system. The largest integrant of the entire immune system is the mucosal immune system which is augmented to provide a defence mechanism against various environmental pathogens at the mucosae. The primary host response towards the pathogen starts from an immune microenvironment of nasopharynx-associated lymphoid tissue (NALT) and mucosa-associated lymphoid tissue (MALT). The presence of exhausted lymphocytes, lymphopenia, pneumonia, and cytokine storm is the hallmark of COVID-19. The multifaceted nature of co-morbidity factors like obesity and type 2 diabetes and their effects on immunity can alter the pathogenesis of SARS-CoV-2 infection. Adipose tissue is a crucial endocrine organ that secretes a plethora of factors like adipokines, cytokines, and chemokines that have a profound impact on metabolism and augment the expression of mucosal pro-inflammatory cytokines, like tumour necrosis factor-alpha (TNF-
), interferon-gamma (IFN-
), and the interleukin-12 (IL-12)/IL-23. Mucosal immunization could be a superior approach to activate mucosal and systemic immune responses against pathogenic invasion at mucosal surface entry ports. Mucosal vaccines are also able to generate strong systemic humoral immunity—required to neutralize any virus particle that dodges the primary immune response. In the case of various vaccines, the weakening of vaccine-induced immunity is associated with breakthrough infections. On the other hand, several lines of evidence suggest that mucosal immunization via natural infection or vaccination induces a more robust immune response in respiratory mucosa, which is the prime target of SARS-CoV-2 infection. To develop an efficient vaccine against mucosal pathogens, contemplation of the design of the delivery route, immunomodulatory features, and adjuvants are very important. In this article, evidence was provided to understand the significant role of mucosal immunity, along with secretory and circulating immunoglobulin A (IgA) antibodies in generating a novel mucosal vaccine against COVID-19. Moreover, along with mucosal vaccines, a look must be given to combination treatment strategies with plant bioactive molecules. Glycan-binding lectins against viral proteins for targeted activation of the mucosal immune response are one such example. These may play a promising role in halting this emerging virus. In this review, the different aspect of mucosal immunization and their probable prospect against the COVID-19 pandemic have been summarized. Further study on the formulation of nasal spray or inhaler with such plant bioactive molecules or engineered antibodies will be a potent therapeutic and prophylactic strategy in the prevention of a larger array of SARS-CoV2 with reduced side effects.