Next Generation Mucosal Vaccine Strategy for Respiratory Pathogens

Abstract

Inducing humoral and cytotoxic mucosal immunity at the sites of pathogen entry has the potential to prevent the infection from getting established. This is different from systemic vaccination, which protects against the development of systemic symptoms. The field of mucosal vaccination has seen fewer technological advances compared to nucleic acid and subunit vaccine advances for injectable vaccine platforms. The advent of the next-generation adenoviral vectors has given a boost to mucosal vaccine research. Basic research into the mechanisms regulating innate and adaptive mucosal immunity and the discovery of effective and safe mucosal vaccine adjuvants will continue to improve mucosal vaccine design. The results from clinical trials of inhaled COVID-19 vaccines demonstrate their ability to induce the proliferation of cytotoxic T cells and the production of secreted IgA and IgG antibodies locally, unlike intramuscular vaccinations. However, these mucosal vaccines induce systemic immune responses at par with systemic vaccinations. This review summarizes the function of the respiratory mucosa-associated lymphoid tissue and the advantages that the adenoviral vectors provide as inhaled vaccine platforms.

Molecular Events in Immune Responses to Sublingual Influenza Vaccine with Hemagglutinin Antigen and Poly(I:C) Adjuvant in Nonhuman Primates, Cynomolgus Macaques

“…Safety concerns regarding Poly(I:C) adjuvants have primarily arisen from studies involving nasal vaccination in mice [ 31 , 32 ]. Notably, humans differ anatomically from mice in lacking defined bronchi-associated lymphoid tissue (BALT), but possessing infection-inducible BALT [ 33 ]. Moreover, differences in the immune systems between rodents and primates have been underscored by genome-based evidence [ 34 ].…”

Viral infections causing asthma exacerbations in the age of biologics and the COVID-19 pandemic

“…Since most respiratory pathogens gain infectivity by breaking the mucosal barrier, providing mucosal immunity would be an early line of defense in preventing infection and therefore transmission to others [ 50 ]. Benefits include increasing IgA production and local mucosal immunity to inhibit viral shedding and preventing the spread from upper respiratory infection to lower respiratory infection [ 51 ]. Recombinant SARS-CoV-2 viral based mucosal vaccines have shown clinical efficacy and are currently being used outside the United States [ 52 , 53 ].…”

Why Should Vaccines against Respiratory Diseases Go Mucosal? B Cell Epitope-Based Vaccines against SARS-CoV-2

“…Mucosal vaccines can lessen viral shedding and transmission as well as prevent viral replication at the vaccination site in the event of re-infection by inducing the production of resident memory B and T cells, which have already encountered the virus and can respond more quickly than systemic memory cells [18]. An additional advantage of mucosal route of vaccination compared to injectable/systemic route, lies on the better homing and formation of specific tissue resident memory CD4 T cells and CD8 T cells, as shown for SARS-CoV-2 [32][33][34].…”