in vivo efficacy of hF5-WT and hF5-LALA dosed prophylactically and therapeutically. Schematic of dosing and infection timeline through 14 dpi (days post infection) survival (a). Prophylaxis study involved a -24-h pre-infection 100ug dose of Ab (b), while therapeutic studies included +24hpi (c), +48-h (d), and +72-h (e) post-exposure 100ug dose. Animals were infected intranasally (IN) with 5e7pfu VEEV-TC83, and survival was measured to 14dpi. Pre-treatment (-24hpi) and early exposure (+24hpi) animals receiving hF5-WT or hF5-LALA Ab showed comparable survival rates, while in the +48hpi post-exposure context, hF5-LALA-treated animals did exhibit a significant reduction in survival. By +72hpi both hF5-WT and hF5-LALA -treated individuals showed similarly high degrees of mortality, indicating a diminishing therapeutic benefit regardless of Fc effector function, in the context of an established VEEV infection. For the -24hpi (hours post infection) study hIgG1 v. hF5-WT ****p< .0001, hIgG1 v. hF5-LALA ****p < .0001, hF5 v. hF5-LALA was not significant (p = .1034). For the +24hpi study hIgG1 v. hF5-WT ****p< .0001, hIgG1 v. hF5-LALA ****p< .0001, hF5-WT v. hF5-LALA was not significant (p = .7818). For the +48hpi study hIgG1 v. hF5-WT ****p< .0001, hIgG1 v. hF5-LALA ****p< .0001, hF5-WT v. hF5-LALA **p= .0036. For the +72hpi study hIgG1 v. hF5-WT *p = .0190, hIgG1 v. hF5-LALA *p = .0343, hF5-WT v. hF5-LALA was not significant (p= .3751), by Log-rank Mantel-Cox test. In -24hpi and +24hpi studies n=20; in +48hpi studies n=35; and in +72hpi study n=10. Data shown represent at least two experiments, except for the +72hpi study, performed once.