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Inhaled mRNA Respiratory Vaccines to Be Developed Under $20.7 Million Government Contract

Inhaled mRNA Respiratory Vaccines to Be Developed Under .7 Million Government Contract

The Icahn School of Medicine at Mount Sinai Health System has received a five-year federal agreement worth approximately $20.7 million to develop mRNA vaccine technologies targeting respiratory pathogens. The funding comes from the U.S. Department of Defense through the Defense Threat Reduction Agency (DTRA), with support provided through its Joint Science and Technology Office (JSTO) and the Medical CBRN Defense Consortium.1

The project, known as Vaccine Immunoengineering for Targeted Antigen Presentation and Layered Control (VITAL), will initially focus on an experimental nasal vaccine against highly pathogenic avian influenza A (H5N1). Researchers plan to investigate whether the approach can be adapted to target at least 20 respiratory viruses. VITAL will investigate an unmodified messenger ribonucleic acid (mRNA) vaccine administered through the nose.

Messenger RNA provides cells with instructions for making proteins. For example, the mRNA COVID-19 biological manufactured by Pfizer and Moderna programs cells to make synthetic spike protein and the mRNA encoding the SARS-CpV-2 spike protein is delivered into the body coated in lipid nanoparticles to provoke a strong inflammatory response. To develop mRNA nasal vaccines for other respiratory diseases, researchers aim to primarily target macrophages, which as immune cells that help defend the body against infection. The project will examine how this targeted delivery approach affects immune responses and whether it can address safety concerns that have been associated with mRNA biological product development.2

The research will examine five vaccine-design principles: targeting specific immune cells, providing appropriate immune stimulation, modifying antigens to reduce potential toxicity, delivering vaccines through routes relevant to how pathogens enter the body, and adjusting the timing of doses to reproduce aspects of natural infection. Researchers will investigate how these approaches influence immune responses and whether they can be applied to different respiratory pathogens.3 4

Evaluating Immune Responses

Researchers will use animal models and human immune tissue systems to study the experimental mRNA vaccine. They will examine how different immune cells interact, including macrophages and dendritic cells, which help coordinate immune responses, and B cells and T cells, which play roles in recognizing and responding to threats.5

The team will also use laboratory techniques to examine individual cells, study how cells are arranged within tissues, analyze proteins, and process biological data using computational methods. These studies are designed to assess the product’s safety and immune activity before development.6

Funding and Research Goals

The project falls under the Reimagining Available Vaccines and Envisioning Novelty (RAVEN) program, which supports research into developing novel vaccine technologies to respond to threats by pathogens that could harm human health. Researchers intend to investigate whether the mRNA platform can be extended beyond H5N1 to other respiratory viruses. The agreement runs through Aug. 28, 2031, and includes preclinical research and regulatory planning for possible future clinical development.7


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