TY - JOUR
T1 - Vectored long-term co-delivery of antibodies for SARS-CoV-2, RSV and Influenza prophylaxis
AU - Lende, Stine Sofie Frank
AU - Rothemejer, Frederik Holm
AU - Andreas, Malthe
AU - Pedersen, Maria Lange
AU - Traberg-Nyborg, Laura
AU - Iversen, Emma Falling
AU - Juhl, Anna Karina
AU - Søgaard, Ole Schmeltz
AU - Schleimann, Mariane Høgsbjerg
AU - Tolstrup, Martin
N1 - Publisher Copyright:
© 2025
PY - 2025/9
Y1 - 2025/9
N2 - 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.
AB - 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.
KW - AAV
KW - Co-delivery
KW - Gene-therapy
KW - Immuno-prophylaxis
KW - Influenza
KW - RSV
KW - SARS-CoV-2
UR - http://www.scopus.com/inward/record.url?scp=105005771696&partnerID=8YFLogxK
U2 - 10.1016/j.virol.2025.110573
DO - 10.1016/j.virol.2025.110573
M3 - Journal article
C2 - 40413832
AN - SCOPUS:105005771696
SN - 0042-6822
VL - 610
JO - Virology
JF - Virology
M1 - 110573
ER -