Dealing with a mucosal viral pandemic: lessons from COVID-19 vaccines

Abstract

The development and deployment of vaccines against COVID-19 demonstrated major successes in providing immunity and preventing severe disease and death. Yet SARS-CoV-2 evolves and vaccine-induced protection wanes, meaning progress in vaccination strategies is of upmost importance. New vaccines directed at emerging viral strains are being developed while vaccination schemes with booster doses and combinations of different platform-based vaccines are being tested in trials and real-world settings. Despite these diverse approaches, COVID-19 vaccines are only delivered intramuscularly, whereas the nasal mucosa is the primary site of infection with SARS-CoV-2. Preclinical mucosal vaccines with intranasal or oral administration demonstrate promising results regarding mucosal IgA generation and tissue-resident lymphocyte responses against SARS-CoV-2. By mounting an improved local humoral and cell-mediated response, mucosal vaccination could be a safe and effective way to prevent infection, block transmission and contribute to reduce SARS-CoV-2 spread. However, questions and limitations remain: how effectively and reproducibly will vaccines penetrate mucosal barriers? Will vaccine-induced mucosal IgA responses provide sustained protection against infection?

Assessment of the Humoral Immune Response Following COVID-19 Vaccination in Healthcare Workers: A One Year Longitudinal Study

“…However, inducing superior anti-SARS-CoV-2 mucosal immunity using innovative vaccines remains an important goal in stopping viral transmission. Several preclinical studies show that intranasal or orally administered adenoviral-based vaccines can protect against transmission and reduce disease severity [ 17 ], inducing mucosal specific IgA and tissue-resident memory cells [ 18 ].…”

Mucosal immunity: The missing link in comprehending SARS-CoV-2 infection and transmission

“…Among these it is notable that intranasal vaccination has been successfully developed against influenza virus, thereby affording precedent for this approach against SARS-CoV-2. Numerous groups have indeed taken up the challenge and demonstrated that intranasal immunization with a variety of vaccine constructs can induce antibodies with virus-neutralizing capability in secretions as well as serum, and even protective immunity against challenge, in animals such as mice ( 86 , 87 ), hamsters ( 88 , 89 ), and monkeys ( 90 , 91 , reviewed in 92 , 93 ). However, few of these efforts have advanced into clinical trials beyond phase I.…”

Fully Quantitative Measurements of the Antibody Levels for SARS-CoV-2 Infections and Vaccinations calibrated against the NISTmAb Standard IgG Antibody

“…The prevention of infection implies a mechanism that is either a rapid antibody and T cell response to a pre-symptomatic viral load, or the prevention of cellular infection completely by opsonisation and neutralisation. The pure prevention mechanism is consistent with mucosal immunity [25][26][27] and allows decoupling of the antibody levels from T and B cell memory responses that require infected cells to trigger the adaptive response. Further, the total T cell density in the mucosa is ~650 mm -2 , varying over a factor of five 14 , and would increase response once epithelial cells have been infected by inducing recruitment of further T cells from the blood.…”