Thursday, November 16, 2023
Uncas A. Whitaker Hall, 218
6760 Forest Park Pkwy, St. Louis, MO 63105, USA
Presenting on “Targeted In Vivo Gene Delivery via Tropism Modified Adenoviral Vectors - A Thirty Year Quest for the Holy Grail”.
David T. Curiel, MD, PhD, professor of radiation oncology at Washington University School of Medicine, will speak on Thursday, November 16, 2023 at 10:00 am CST in Whitaker 218.
Vaccines developed and employed to counteract the COVID-19 pandemic have achieved remarkable success in reducing morbidity, hospitalizations, and mortality due to SARS-CoV-2 infection. Nonetheless, the current vaccines have a number of limits which have spurred the development of novel approaches and platforms. Among these, intranasal immunization has been proposed as a strategy to traverse the limits of approved COVID-19 vaccines (1-3). A recent editorial in Science Immunology highlighted the urgency to accelerate intranasal vaccine technology through an “Operation Warp Speed”-type initiative (4). Indeed, a recent White House COVID-19 Summit prioritized the development of intranasal vaccine agents for rapid clinical deployment.
The recent interest in intranasal vaccination has arisen because of the failure of the highly successful COVID-19 vaccines in stopping breakthrough infection and transmission, especially against emerging variant viruses Based on preliminary pre-clinical data, and a goal of achieving high levels of durable immunity at the point of virus attack in the upper respiratory tract, mucosal immunization could provide a viable solution that addresses these limitations (1, 5, 6).
Our efforts have been at the forefront of exploring an intranasal vaccine for COVID-19. In this regard, our group established the utility of a simian adenoviral (SiAd) vaccine vector (ChAd-SARS-CoV-2) to achieve effective protective immunity against SARS-CoV-2 in animals (7, 8). Of note, we demonstrated that superior and even sterilizing immunity could be achieved via intranasal delivery of adenoviral-vectored vaccines (9). Our vaccine was translated into human clinical trials (BBV154, Bharat Biotech) where emergency use approval in India was granted in September of 2022 (iNCOVACC).
Here we seek to advance the design of intranasal adenoviral-vectored vaccines by addressing several of the key barriers to generating optimal mucosal immunity after intranasal inoculation. One major challenge in developing intranasal vaccines is to deliver antigens to the antigen presenting cells (APCs) within the respiratory tract. We will use specific vector-modifying strategies to enhance immunogen access to antigen presenting cells within the airway mucosa. Our proposal will provide the critical proof-of-concept required to develop and test a biologically-targeted SiAd vaccine that enhances mucosal immunity in this case against SARS-CoV-2. If successful, this technology will have broad potential utility for developing effective against viruses that infect the respiratory tract and are transmitted by the aerosol or droplet route.