IL6 and Sepsis: Three key findings support clinical development: (i) Broad strain coverage demonstrated by 5C8’s maintained binding to prevalent PcrV mutants (L6F/A9G/S21P/S225R) (Fig. 3B); (ii) cytokine modulation via 60–82% IL-6 reduction (P < 0.01) (Fig. 4G and H) suggests 5C8 may mitigate sepsis-associated cytokine storms—a critical advantage over pure bactericidal agents (42); and (iii) pharmacodynamic resilience: LALA-mutated 5C8 retained full efficacy (Fig. 5C), enabling Fc engineering to extend half-life without compromising function (31).