Mucosal vaccines for SARS-CoV-2: scientific gaps and opportunities—workshop report

Abstract

On November 7th and 8th, 2022, The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), The Coalition for Epidemic Preparedness Innovation (CEPI), The Bill & Melinda Gates Foundation (BMGF), The Biomedical Advanced Research and Development Authority (BARDA), and the Wellcome Trust hosted a virtual workshop entitled “Mucosal Vaccines for SARS-CoV-2: Scientific Gaps and Opportunities.” During the workshop, researchers and vaccine developers from around the world discussed the potential of mucosal vaccines to block SARS-CoV-2 transmission and reviewed the status of SARS-CoV-2 mucosal vaccine research. Here, we summarize key challenges and opportunities in basic, translational, and clinical research that were highlighted during the meeting. We also provide recommendations to advance the field and accelerate the development of mucosal vaccines for SARS-CoV-2.

Clinical Assessment of SARS-CoV-2 Antibodies in Oral Fluids Following Infection and Vaccination

“…From a clinical standpoint, threshold values of spike- and nucleocapsid-specific IgG and/or SIgA in mucosal sites may serve as more specific and accessible indicators of immunity compared to immunoglobulins found in serum/plasma, potentially influencing decisions about the need for booster vaccinations in high-risk and vulnerable populations ( 17 , 18 ). From the vantage point of vaccine research, an outsized role for SIgA in immunity to SARS-CoV-2 would justify investments in intranasal vaccine platforms designed to target mucosal-associated lymphoid tissues and stimulate local humoral (and cellular) responses ( 4 , 19 ). However, claims about the importance of serum- and local-derived antibodies in immunity to SARS-CoV-2 in human populations can only be substantiated if methods and reagents associated with the collection and analysis of OF are optimized, standardized, and harmonized across laboratories.…”

“…There is increasing recognition that the mucosal immune system and local secretory antibodies in oral fluids (OF) and nasopharyngeal (NP) fluids may be a barrier to reinfection as well as an impediment to SARS-CoV-2 shedding and transmission, especially in the case of Omicron ( 4 , 5 ). Following inhalation, SARS-CoV-2 replication can occur in the cells that line the upper respiratory tract, including the salivary glands that express the requisite SARS-CoV-2 receptors ACE2 and TMPRSS ( 6 ).…”

An Overview of SARS-CoV-2 Etiopathogenesis and Recent Developments in COVID-19 Vaccines

“…Convidecia Air is similar to the Ad5-SARS-CoV-2 vaccine but given by inhalation and developed and approved in China. This vaccine elicited an increased level of bronchial IgA levels [77]. The Sputnik V (Gam-COVID-Vac) was developed at Gamaleya National Research Centre for Epidemiology and Microbiology (Moscow, Russia).…”

Realising the potential of correlates of protection for vaccine development, licensure and use: short summary

“…For each pathogen, mechanisms of protection may be different at different stages of infection and for different indications or endpoints. COVID-19 provides an example: Whilst there is no validated CoP for prevention from infection at mucosal surfaces, neutralising antibodies and T cells may provide protection in the upper airway, whereas protection in the lungs includes the role of binding antibodies through Fc, anamnestic antibodies and T cells, with the most severe outcomes of COVID-19 likely to require multiple branches of adaptive immunity acting synergistically 13 , 14 . Correlates of protection may also differ between populations, for example because of past exposure to infections, or by age (e.g.…”