Activation of mucosal immunity and novel prophylactic and therapeutic strategy in combating COVID-19

Abstract

Coronavirus disease 2019 (COVID-19) emerges 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). Prognosis 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 surface like nasal, oral mucosae, and/or the conjunctival surface of the eye where it has interacted along with the immune system. 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 its 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 augments the expression of mucosal pro-inflammatory cytokines, like tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), 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. To develop an efficient vaccine against mucosal pathogens, considering the designing of the delivery route, immunomodulatory features, and adjuvants are very important. In this article, we further provide evidence 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, we should look for combination treatment strategies with plant bioactive molecules. Glycan-binding lectins against viral proteins for targeted activation of mucosal immune response are one of such examples. This might play a promising role to halt this emerging virus.

The use of RNA-based treatments in the field of cancer immunotherapy

“…The intradermal vaccination led to a high activation of TLR7 in both mice and humans, as well as TLR8 in humans [117]. This immunization also led to the production of type I interferon, as well as pro-inflammatory cytokines and chemokines [118]. In a similar vein, it was shown that RNAdjuvant (CureVac AG), which is an unmodified, single-stranded RNA that is stabilized by a cationic carrier peptide, had adjuvant effect in the context of vaccines that do not include messenger RNA [119].…”

Understanding Mucosal Physiology and Rationale of Formulation Design for Improved Mucosal Immunity

“…Mucosal tolerance is an active immune response that is regulated by several tissue and cells in our body . MALT is an essential part of mucosal immunity, which is considered primary tissues where inhaled or ingested viruses are lodged. − Also, the mouth, pharynx, and esophagus, as well as the gastrointestinal, respiratory, and urogenital systems, are all considered mucosal tissues, which play an important role in mucosal immunity.…”

Is COVID-19 really a geriatric syndrome?

“… Delay in identifying viral pathogens: This delay worsens the patients’ prognosis by leading to critical conditions such as acute respiratory distress syndrome (ARDS) ( Bhatnagar et al, 2021 , Liu et al, 2019 ). Altered production of defensive barriers: Lack of mucins and glycoproteins contributes to an unchallenging entrance of viral pathogens ( Chatterjee et al, 2021 , Xu et al, 2019 ). Intrathymic infiltration of adipose tissue: By affecting the production of T cells and memory lymphocytes, this could result in a compromised function of the adaptive immune system against SARS-CoV-2 ( Ongrádi and Kövesdi, 2010 ).…”

“…Altered production of defensive barriers: Lack of mucins and glycoproteins contributes to an unchallenging entrance of viral pathogens ( Chatterjee et al, 2021 , Xu et al, 2019 ).…”