Lung-targeting lentiviral vector for passive immunisation against influenza

Area of Science:

• Virology
• Immunology
• Gene Therapy

Background:

• Recombinant simian immunodeficiency virus (SIV) vectors are utilized for gene delivery.
• Targeting respiratory tissues presents challenges for effective gene therapy.

Purpose of the Study:

• To evaluate the efficacy of a novel SIV vector pseudotyped with Sendai virus glycoproteins (rSIV.F/HN) for lung-specific gene expression.
• To assess the potential of this vector for inducing protective immunity against influenza.

Main Methods:

• Construction of recombinant SIV pseudotyped with F and HN glycoproteins from murine respiratory Sendai virus.
• Administration of a single dose of rSIV.F/HN to mice.
• Assessment of transgene expression in murine airways and systemic circulation.
• Evaluation of neutralizing antibody production against influenza.
• Influenza challenge experiments to determine protection.

Main Results:

• The rSIV.F/HN vector demonstrated efficient lung cell targeting and lifelong transgene expression in murine airways.
• A single dose induced stable expression of neutralizing antibodies against influenza.
• Mice were protected against lethal challenge with two different influenza strains.

Conclusions:

• The rSIV.F/HN vector is a promising tool for passive immunization strategies against influenza and other respiratory pathogens.
• This vector facilitates sustained antibody expression in the respiratory tract and systemically.
• Potential applications include prophylaxis and treatment of respiratory viral infections.