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ARS Home » Southeast Area » Stoneville, Mississippi » Warmwater Aquaculture Research Unit » Research » Publications at this Location » Publication #375734
Research Project: Biophotonics - The Application of Novel Imaging Methodologies to Livestock Production Research

Location: Warmwater Aquaculture Research Unit

Title: Aerosol delivery of synthetic mRNA to vaginal mucosa leads to durable expression of broadly neutralizing antibodies against HIV

Author
item LINDSAY, KEVIN - Emory University
item VANOVER, DARYLL - Emory University
item THORESEN, MERRILEE - Mississippi State University
item KING, HEATH - Mississippi State University
item XIAO, PENG - University Of Louisiana
item PERES, BADIAL - Mississippi State University
item ARAINGA, MARILUZ - University Of Louisiana
item PARK, SEONG - Mississippi State University
item TIWARI, POOJA - Emory University
item PECK, HANNAH - Emory University
item BLANCHARD, EMMELINE - Emory University
item FEUGANG, JEAN - Mississippi State University
item OLIVIER, ALICIA - Mississippi State University
item ZURLA, CHIARA - Emory University
item VILLINGER, FRANCOIS - University Of Louisiana
item WOOLUMS, AMELIA - Mississippi State University
item SANTANGELO, PHILIP - Emory University

Submitted to: Molecular Therapy
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/14/2019
Publication Date: 1/10/2020
Citation: Lindsay, K., Vanover, D., Thoresen, M., King, H., Xiao, P., Peres, B., Arainga, M., Park, S., Tiwari, P., Peck, H., Blanchard, E., Feugang, J., Olivier, A., Zurla, C., Villinger, F., Woolums, A., Santangelo, P. 2020. Aerosol delivery of synthetic mRNA to vaginal mucosa leads to durable expression of broadly neutralizing antibodies against HIV. Molecular Therapy. 28(3):805-819.

Interpretive Summary: Human immunodeficiency virus (HIV) remains a substantial public health burden worldwide, with 36 million people infected and 1.8 million new cases per year. More than 90% of infections occur via sexual contact and the estimated probability of infection of the female genital tract (FRT) is 1 in 200–2,000 per coital act, depending on the viral burden in the donor. There is a clear need for low-cost, self-applied, long-lasting approaches to prevent human immunodeficiency virus (HIV) infection in both men and women, even with the advent of pre-exposure prophylaxis (PrEP). Broadly neutralizing antibodies represent an option to improve HIV prophylaxis, but intravenous delivery, cold-chain stability requirements, low cervicovaginal concentrations, and cost may preclude their use. The current findings present a new paradigm to deliver neutralizing antibodies to the female reproductive tract for the prevention of HIV infections.

Technical Abstract: Here, we present an approach to express the anti-GP120 broadly neutralizing antibody PGT121 in the primary site of inoculation, the female reproductive tract, using synthetic mRNA. Expression is achieved through aerosol delivery of unformulated mRNA in water. We demonstrated high levels of antibody expression for over 28 days with a single mRNA administration in the reproductive tract of sheep. In rhesus macaques, neutralizing antibody titers in secretions developed within 4 h and simian-HIV (SHIV) infection of ex vivo explants was prevented. Persistence of PGT121 in vaginal secretions and epithelium was achieved through the incorporation of a glycosylphosphatidylinositol (GPI) anchor into the heavy chain of the antibody.