Immunology

The COVID-19 pandemic has had a profound impact on the world, affecting every aspect of life, from work to travel, education to healthcare. While several vaccines have been developed and authorized for emergency use, the race to produce a more effective and convenient vaccine continues. One promising approach is the mucosal COVID-19 vaccine. Unlike traditional vaccines, which rely on injection into muscle tissue, mucosal vaccines are administered via the nose, mouth, or rectum, where the virus enters the body. This approach offers several advantages, including inducing immunity at the site of infection and reducing the severity of symptoms. However, mucosal vaccines also pose several challenges, including technical hurdles and regulatory barriers. In this article, we explore the potential and challenges of mucosal COVID-19 vaccines, their development, and the implications for the fight against the pandemic.


The National Institute of Allergy and Infectious Diseases (NIAID) recently organized a virtual workshop in collaboration with various organizations to discuss the importance and challenges of developing mucosal vaccines for SARS-COV-2. The report on the highlights of this workshop has now been published in npj Vaccines. The researchers acknowledge the need for improvements in the currently available COVID-19 vaccines. A vaccine that is more effective at preventing transmission or infection with SARS-CoV-2 can reduce the overall replication of the virus, thus reducing the burden of the disease. Therefore, a mucosal vaccine that promotes an immune response in the respiratory tract could effectively block transmission and infection.

The NIAID partnered with the Coalition for Epidemic Preparedness Innovation, the Bill and Melinda Gates Foundation, the Biomedical Advanced Research and Development Authority, and the Wellcome Trust to develop the workshop. The two-day event consisted of eight virtual sessions where vaccine researchers and developers discussed the challenges and priorities in mucosal vaccine development. One of the challenges is identifying and verifying new correlates of protection to evaluate if a vaccine improves recipients’ mucosal immune response to SARS-CoV-2. An improved animal model is also needed to develop potential mucosal vaccines. Careful clinical design is necessary to assess the unique safety concerns related to mucosal vaccines and evaluate if the vaccine can block the transmission of the virus.

The researchers also highlighted the need for trial designs that account for how the vaccine will be used as most people either received a SARS-CoV-2 vaccine or had a natural infection. Mucosal vaccines will likely be used as boosters, and researchers will need to know how well vaccines function in people who have some prior immunity. The means of delivery must also be considered, including nasal sprays, pills, liquids, and nebulizers, which can deliver the vaccine more directly to the respiratory system.

Despite the challenges, the researchers are optimistic about the future of mucosal vaccines for COVID-19. They concluded that mucosal vaccine development is a priority considering the potential benefits a successful vaccine could bring. Such research would also lead to improved vaccines for other diseases, such as influenza, respiratory syncytial virus, tuberculosis, in addition to advancing COVID-19 vaccinology.

NIAID conducts and supports research to study the causes of infectious and immune-mediated diseases and to develop better means of preventing, diagnosing, and treating these illnesses. The organization provides news releases, fact sheets, and other related materials on its website. The National Institutes of Health (NIH) is the nation’s medical research agency, including 27 Institutes and Centers, and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, investigating the causes, treatments, and cures for both common and rare diseases. For more information on NIH and its programs, visit their website.


In conclusion, the development of mucosal COVID-19 vaccines offers new hope in the fight against the pandemic. Although there are still numerous challenges to overcome, including the delivery system, dosage, and standardization of testing, the potential benefits make it a promising avenue of research. If successful, mucosal vaccines could bring about a new era of immunization and help us effectively combat the spread of COVID-19. However, it is important to remember that vaccination is just one aspect of the overall response to the pandemic, and we must continue to practice social distancing, wear masks, and follow other guidelines until the situation is fully under control.

Since the onset of the COVID-19 pandemic, scientists worldwide have been tirelessly working on the development of vaccines to curb the spread of the virus. While several vaccines have been developed and authorized for use, there is still a need to explore more efficient and effective ways to combat the virus. One promising approach that has gained attention in recent times is mucosal COVID-19 vaccines. These vaccines could potentially offer several advantages over the current intramuscular shots. However, there are also a few challenges that need to be addressed before they can become a mainstream option. This article aims to explore the potential and challenges of mucosal COVID-19 vaccines.


The National Institute of Allergy and Infectious Diseases (NIAID) co-hosted a virtual workshop on the importance and challenges of developing mucosal vaccines for SARS-CoV-2 in November 2022. The report highlights from the workshop have been published in the npj Vaccines journal. While the available COVID-19 vaccines are effective at preventing severe disease, hospitalization, and death, a vaccine that could inhibit transmission or infection with SARS-CoV-2 would reduce the viral replication and associated disease burden. Since SARS-CoV-2 enters the body and is transmitted via the respiratory tract, vaccines that promote a mucosal immune response in the respiratory tract could be better at blocking transmission and infection. However, no COVID-19 mucosal vaccines have been authorized for use by regulatory agencies in the United States or Europe yet, though at least 44 mucosal vaccines are in preclinical development.

NIAID teamed up with other organizations, including the Coalition for Epidemic Preparedness Innovation, the Bill and Melinda Gates Foundation, the Biomedical Advanced Research and Development Authority, and the Wellcome Trust, to develop the workshop. During the two-day event, vaccine researchers and developers virtually met in eight sessions to discuss challenges and priorities in mucosal vaccine development. For instance, new correlates of protection must be identified and verified to evaluate whether a vaccine enhances recipients’ mucosal immune responses to SARS-CoV-2 to facilitate clinical testing and regulatory approval.

The report states that improved animal models are necessary to help researchers develop potential mucosal vaccines. Careful clinical design is needed to evaluate unique safety concerns related to mucosal vaccines, and whether a vaccine can prevent virus transmission must also be appropriately evaluated. Trials that account for how vaccines will be used also require careful design, as mucosal vaccines will likely be used as boosters since most people have already received the SARS-CoV-2 vaccine. Researchers must understand how well the vaccines function in individuals who have some prior immunity.

The means of delivery must also be considered since various delivery mechanisms could deliver a vaccine more directly to the respiratory system, including nasal sprays, pills, liquids taken orally, and nebulizers. Each mechanism presents unique challenges in terms of production, testing, and delivery. However, despite many challenges to mucosal vaccine development, workshop attendees remained optimistic about the future of mucosal vaccines for COVID-19. The researchers concluded that research efforts related to mucosal vaccine development should be a priority, given the potential benefits that a successful candidate could bring. Such research could also lead to improved vaccines for other diseases, such as influenza, respiratory syncytial virus, or tuberculosis, in addition to advancing COVID-19 vaccinology.

NIAID conducts and supports research worldwide to study the causes of infectious and immune-mediated diseases and to develop better means of preventing, diagnosing, and treating such illnesses. NIH includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services that investigates the causes, treatments, and cures for both common and rare diseases.


In conclusion, the development and deployment of mucosal COVID-19 vaccines hold incredible potential for controlling the spread of the virus and achieving herd immunity. The ability to target the virus at the site of entry through the use of these vaccines is a major advantage over traditional injectable vaccines. However, there are also significant challenges to overcome, such as delivery methods and regulatory hurdles. Nonetheless, with continued research and innovation, mucosal vaccines could play a critical role in ending the COVID-19 pandemic and preventing future outbreaks. It is important to recognize the significant advances made in this field and to support ongoing efforts to further optimize and scale these promising vaccines.