NUS Medicine-Monash Study: Intranasal Vaccine Booster Enhances Immune Response and Protection Against Sarbecoviruses
A groundbreaking study conducted by researchers at the NUS Yong Loo Lin School of Medicine and Monash University has revealed a novel vaccine booster candidate administered via the nasal route, which significantly boosts immunity in the respiratory tract. This research offers a promising strategy to enhance immunity and inform future booster approaches, potentially revolutionizing how we combat infectious diseases.
The study, published in The Journal of Clinical Investigation, highlights the effectiveness of intranasal vaccine boosters in conferring stronger and broader immune responses, as well as robust neutralizing antibody and resident T cell responses in the lung and nasal tissues. This approach outperforms conventional mRNA booster vaccinations, providing a more effective method for delivering vaccine boosters that may offer stronger protection against infections and maintain optimal immunity.
Led by Associate Professor Sylvie Alonso and Dr. Nicholas Cheang, both from the Department of Microbiology and Immunology and the Infectious Diseases Translational Research Programme at NUS Medicine, the study examined alternative vaccine booster candidates and administration methods to improve protective immunity and longevity against sarbecoviruses. These viruses, including SARS-CoV-2 (COVID-19) and SARS-CoV-1 (2003 SARS outbreak), are a category of coronaviruses that can cause respiratory infections.
The researchers developed Clec9AOMNI, a dendritic cell-targeting booster vaccine that carries the receptor-binding domain (RBD) from SARS-CoV-2 Omicron XBB.1.5 and SARS-CoV-1 viruses. Dendritic cells are innate immune cells crucial for initiating adaptive immune responses, including antibody and T-cell responses. In the study, laboratory models vaccinated with mRNA COVID-19 vaccines three months prior received a single intranasal dose of Clec9AOMNI. Immune responses were assessed in the blood and respiratory tract for up to six months, alongside efficacy against SARS-CoV-2 Omicron infection.
The study's findings are remarkable. Compared to intramuscular mRNA booster vaccination, nasal boosting with Clec9AOMNI induced significantly stronger neutralizing antibody responses, robust T-cell responses in the lungs and nasal tissues, and sustained immunity for at least six months. This approach also provided stronger protection against SARS-CoV-2 (Omicron) infection, with undetectable virus in the lung and nasal tissues.
The study suggests that Clec9AOMNI has the potential to address the current shortcomings of COVID-19 mRNA vaccines, such as waning immunity, inadequate mucosal immunity, and limited breadth, as it does not provide protective coverage against sarbecoviruses beyond the SARS-CoV-2 family. With its ability to confer broad and long-lasting protective immunity against SARS-CoV-2 variants, Clec9AOMNI may eliminate the need for repeated booster shots and contribute to maintaining optimal immunity at a population level.
Associate Professor Alonso emphasized the significance of this research, stating, 'While existing vaccines remain highly effective at preventing severe disease, their protection against infection and transmission decreases within months, partly because they generate little immunity at mucosal surfaces such as the nose and lungs. Our findings suggest that the intranasal Clec9AOMNI vaccine candidate addresses these shortcomings and may better protect the elderly and other vulnerable groups who are unable to receive conventional intramuscular vaccine administration.'
The harsh mucosal environment can lead to rapid degradation of vaccine components before effective immune responses are induced, making nasal administration challenging. However, the Clec9A targeting vaccine platform offers a promising solution by ensuring vaccine efficacy and longevity at the respiratory tract.
Collaborator Associate Professor Mireille Lahoud from the Monash Biomedicine Discovery Institute at Monash University noted, 'Targeting dendritic cells through the Clec9A platform opens a new avenue for vaccine design. By leveraging the role of dendritic cells in orchestrating immune responses, the study highlights the promise of intranasal booster vaccines in preventing infection at the point of viral entry.'
The researchers plan to further validate their findings to ensure their relevance to human anatomical structures and immune landscapes. Ultimately, they aim to apply this approach to other infectious and non-infectious diseases in preparation for future pandemics and health crises, harnessing its ease of deployment and versatility at a low cost.
This research is supported by the Singapore Ministry of Health through the National Medical Research Council (NMRC) Office and MOH Holdings Pte Ltd through the Programme for Research in Epidemic Preparedness and REsponse (PREPARE), under project ID PREPARECS1-2022-002.
For media inquiries, please contact:
Olivia Choo
Communications Executive
Yong Loo Lin School of Medicine, National University of Singapore
DID: +65 9056 7410
Email: medv4000@partner.nus.edu.sg
Toni Brient
Media and Communications Manager
Monash University
Telephone: +61 423 964 191
Email: toni.brient@monash.edu
