Y. Xu, T. Ferguson, O. Vest, K. Smith, M. Tsuji, X. Kong, C. Tison
Luna Labs USA,
Keywords: Carbon nanotube, HIV-1 vaccine, mRNA
Summary:1Luna Labs USA, LLC, Biotech Group, 706 Forest Street, Suite A, Charlottesville VA 22903; 2HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, Columbia University, New York, NY 10027; 3Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016; Email: firstname.lastname@example.org Tel: 434-220-1553 Vaccines prevent millions of individuals from suffering from severe sickness and save numerous lives every year. Significant research has therefore gone into the development of a vaccine for Human Immunodeficiency Virus (HIV), which continues to remain a global disease epidemic. As a result, developing safe and effective preventives for HIV remains the hope for controlling the global AIDS epidemic. Mucosal vaccines administered by intranasal delivery using modified viral glycoproteins, or mRNA encoding for them, are being developed by our team at Luna Labs and offer several advantages over systemic delivery by allowing non-invasive application, eliciting both systemic and mucosal immune responses. Such vaccines will be more effective in preventing infection, given that most HIV infections result from mucosal transmission. Recently, mRNA vaccines have emerged as a promising alternative to conventional vaccine approaches because of their high potency, capacity for rapid development, and potential for low-cost manufacture. Despite the advantages of mRNA vaccines, challenges remain, especially due to toxicity of the delivery vehicle. As a result, there is a necessity to formulate mRNA vaccines with novel and effective delivery systems to overcome these obstacles and provide functional vaccination. Luna Labs is developing a carbon nanotube delivery platform (NanoVac) that can co-deliver mRNA and HIV-1 glycoproteins to the immune system. We demonstrated gram scale production of NanoVac with high purity (>99%). We modified mRNA to increase the protein translation and demonstrated NanoVac could stabilize the loaded mRNA from degradation in refrigerator for at least three months. Surface chemistries of NanoVac were optimized to guide antigen/mRNA density and presentation. This was a critical step, where mimicking the virus and surface epitope presentation enhanced immunization. Multiple administration routes were designed/engineered for compatibility with both intramuscular and intranasal administration. NanoVac candidates demonstrated the immunogenicity in rabbits. In Humanized mouse (HIS) studies, the candidates induced human-derived humoral and cellular responses. In the efficacy studies, 33% of the HIV-1-infected mice vaccinated with NanoVac-mRNA were cleared of virus infection by 8 weeks post infection. In toxicity studies for both subcutaneous and intranasal administration, NanoVac was clinically well-tolerated at up to 30 mg/kg in rats. There were no biologically relevant effects on body or organ weights, hematology, or clinical biochemistry parameters. Currently, Luna Labs is working to scale-up the delivery platform and exploring alternate indications for use. Research reported in this abstract is supported by National Institute of Mental Health (NIMH), National Institutes of Health (NIH) under award number 1R44MH133249. This project has been funded in whole or in part with Federal fund from National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services, under Contract No. 75N93019C00034.