Abstract
Adeno-associated virus (AAV) vector mediated expression of therapeutic monoclonal antibodies is an alternative strategy to traditional vaccination to generate immunity in immunosuppressed or immunosenescent individuals. In this study, we vectorized a human monoclonal antibody (31C2) directed against the spike protein of SARS-CoV-2 and determined the safety profile of this AAV vector in mice and sheep as a large animal model. In both studies, plasma biochemical parameters and hematology were comparable to untreated controls. Except for mild myositis at the site of injection, none of the major organs revealed any signs of toxicity. AAV-mediated human IgG expression increased steadily throughout the 28-day study in sheep, resulting in peak concentrations of 21.4–46.7 µg/ mL, demonstrating practical scale up from rodent to large animal models. This alternative approach to immunity is worth further exploration after this demonstration of safety, tolerability, and scalability in a large animal model.
Highlights
IntroductionMonoclonal antibody (mAb) therapies have become a popular strategy for combatting infectious diseases, especially those without licensed vaccines or effective therapeutic treatment [1–3]
Differences in the human IgG (hIgG) levels in both the plasma and BAL fluid (BALF) varied based on sex differences and dueand to variability during during
Vaccines require robust mune functionimmune in those age 65 or older, as well immunity as immunocompromised individuals, leads endogenous response to provide and the age-related decline in the to increased vulnerability to infection and a decrease in vaccine responsiveness immune function in those age 65 or older, as well as immunocompromised individuals, Studies show the effectiveness of influenza vaccines areareduced as much as 50%responsiveness in those 65 leads to increased vulnerability to infection and decrease in vaccine years of age or older compared to young adults
Summary
Monoclonal antibody (mAb) therapies have become a popular strategy for combatting infectious diseases, especially those without licensed vaccines or effective therapeutic treatment [1–3]. Though mAbs are effective as therapeutics, production of clinical grade mAbs for passive immunization is costly and the resulting immunity is short-lived [8]. An alternative approach to passive immunization is vectorized antibody expression, in which an adenoassociated virus (AAV) vector is used to transfer a mAb gene to host cells that subsequently produce and secrete antibody into the blood [9,10].
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