Vectored long-term co-delivery of antibodies for SARS-CoV-2, RSV and Influenza prophylaxis.

Immunocompromised patients are at greater risk of severe courses of common respiratory infections like SARS-CoV-2, RSV and Influenza, while simultaneously benefitting less from protective vaccinations. Monoclonal antibodies (mAbs) against SARS-CoV-2, RSV and Influenza are effective at disease treatment, but costly and impractical as long-term prophylaxis. Vectored immunoprophylaxis is an attractive alternative, allowing continuous production of mAbs by the recipient's own cells. Here, we show that the anti-SARS-CoV-2 mAb A23.58.1 delivered through an adeno-associated virus serotype 8 (AAV8) viral vector intramuscularly leads to dose-dependent sustained antibody expression, protecting mice from SARS-CoV-2 infection. Further, we demonstrate that AAV8-vectored co-delivery of A23.58.1, alongside anti-RSV mAb Nirsevimab, and anti-Influenza mAb 1000-3B04, at a physiologically relevant level for viral protection, is possible. This approach could be a valuable alternative to mAb treatment in immunocompromised populations by conferring long-term antibody expression and prophylaxis following a single intramuscular injection. Further, co-delivery of several antibodies simultaneously demonstrates the feasibility of generating broad and robust antiviral gene therapies in the future.