Characterization of an mRNA-Encoded Antibody Against Henipavirus

Area of Science:

• Virology
• Immunology
• Biotechnology

Background:

• Nipah and Hendra viruses are lethal zoonotic pathogens with no approved treatments.
• Messenger RNA (mRNA) technology allows for endogenous protein expression and potential cost reduction.

Purpose of the Study:

• To develop and evaluate mRNA-based lipid nanoparticles (mRNA-1E5-LNPs) for expressing a henipavirus-neutralizing antibody (1E5).
• To assess the efficacy of mRNA-1E5-LNPs as a prophylactic treatment against henipaviral infections.

Main Methods:

• Systematic screening of untranslated regions (UTRs) to optimize mRNA for antibody expression.
• Generation of mRNA-1E5 encapsulated in lipid nanoparticles (LNPs).
• In vitro and in vivo (BALB/c mice) evaluation of antibody expression, safety, and protection against Hendra pseudoviruses.

Main Results:

• mRNA-1E5-LNPs achieved functional antibody expression levels exceeding 1500 ng/mL in vitro.
• Intravenous administration in mice showed rapid antibody elevation without toxicity.
• Prophylactic administration of mRNA-1E5-LNPs effectively blocked Hendra pseudovirus entry, with a single low dose providing good protection.

Conclusions:

• mRNA-1E5-LNPs represent a promising therapeutic strategy for henipaviral infections.
• This approach provides a blueprint for developing mRNA-based antibodies against emerging viral threats.