Mucosal vaccines for COVID-19 ‘should be developed and tested’
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Experts argued for the development of COVID-19 vaccines that can be delivered at the site of infection, but questioned whether it is possible to make a mucosal vaccine that prevents SARS-CoV-2 infection — and not just severe disease.
“COVID infects persons through the nose or upper respiratory tract. While most studies measure antibody levels in the blood, the virus is thought not to spread in the blood and having antibody at the site of infection is important to reduce infection,” Jeffrey I. Cohen, MD, chief of the Laboratory of Infectious Diseases and the Medical Virology Section at the National Institute of Allergy and Infectious Diseases, told Healio. “The current COVID vaccines are given intramuscularly, and there are concerns about the level and duration of antibody detected at the site of infection.”
To assess what level of antibody was present in the nose compared with that in the blood after infection or vaccination, Cohen and colleagues measured SARS-CoV-2 antibody levels in the plasma, nose and saliva using luciferase immunoprecipitation assays. According to the study, these assays are used to measure the antibody that can cause the SAR-CoV-2 spike and nucleocapsid proteins.
The study demonstrated that the level of antibody in the nose — which Cohen noted is the site at which virus often infects people — is less than that in the blood after vaccination.
Additionally, he explained that levels of SARS-CoV-2 antibody in the nose decline more rapidly than antibody levels in the blood after vaccination of infected people, meaning that vaccination of previously infected persons boosts SARS-CoV-2 antibody levels in the blood more than in the nose or saliva.
“Persistently elevated COVID antibody in the blood may not indicate persistence of COVID antibody at mucosal sites such as the nose,” he said. “As such, vaccines delivered to the nose or respiratory tract should be developed and tested.”
In an accompanying editorial, Kathryn M. Edwards, MD, scientific director at the Vanderbilt Vaccine Research Program, and Kathleen M. Neuzil, MD MPH, director of the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine, wrote that this study provides some understanding of the challenges of using parenteral vaccines to stimulate mucosal immunity.
“The vaccines are highly effective in preventing severe disease but not infection,” Edwards told Healio. “The major question is whether we can design a mucosal vaccine that will prevent infection.”
In their paper, Edwards and Neuzil explained that mucosal vaccines with the potential to generate effective local immunity to SARS-CoV-2 in the respiratory tract would be “attractive options.” However, historically, mucosal vaccines have posed unique challenges. They outlined some of these challenges, referencing prototype mucosal vaccines including live-attenuated influenza vaccines (LAIV), such as the nasal spray influenza vaccine.
For example, in initial pivotal pediatric studies, the nasal spray was more effective than the inactivated influenza vaccines in preventing influenza infection. However, the study showed increased all-cause hospitalizations for 6 months after vaccination in children aged 6 through 11 months of age.
Additionally, further studies in adults have not shown enhanced efficacy of LAIV compared with the inactivated vaccine, which Edwards and Neuzil said is likely because adults have previously encountered multiple influenza infections and the ability of LAIV to replicate in the mucosal site in adults is more limited than in children.
Another example of the challenges with intranasal vaccines outlined in the commentary referenced the first licensed mucosal vaccine in Europe — an intranasal inactivated influenza vaccine with a unique adjuvant — that was found to be associated with Bell’s palsy in a significant number of vaccine recipients, leading to the removal of that mucosal vaccine from the European market.
Because of these challenges, Edwards and Neuzil wrote that live mucosal vaccines represent a delicate balance between “over-attenuation” generating “poorly immunogenic responses” and “under-attenuation,” leading to increased rates of local and systemic adverse events.
Despite these challenges and others, such as incomplete knowledge of protective mucosal immune response and ensuring the safety and efficacy of new mucosal adjuvants, Edwards and Neuzil agree with Cohen and colleagues that mucosal vaccines for SARS-CoV-2 should be pursued.
“We propose that the best path to success is the coordinated, multidisciplinary effort that was employed to accelerate the development of the initial parenteral SARS-CoV-2 vaccines,” they wrote. “Such an approach will require a public investment of funds to ensure the best scientific and strategic path forward for development of mucosal vaccines.”
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