Immunogenicity of MT145-WT Compared to MT145K Trimers in CH01 UCA HC-Only Knockin Mice
(A) Schematic showing immunization schedule of CH01 UCA HC-only KI mice with MT145-WT and engineered MT145K trimers. The CH01 UCA HC-only KI mice were immunized twice with 25 μg of the soluble trimer with glucopyranosyl lipid adjuvant stable emulsion (GLA-SE) as adjuvant. Time points for immunization and bleeds are indicated.
(B) ELISA binding of the MT145-WT and MT145K group trimer-immunized CH01 UCA HC-only KI mice serum samples (pre-bleed, Pre; 2 weeks post prime, Bleed #1; and 2 weeks post boost-1, Bleed #2) with soluble MT145K SOSIP and its glycan knockout variant (MT145K N160K) trimers.
(C) Neutralization titrations of the MT145-WT and MT145K group trimer immunized CH01 UCA HC-only KI mice sera (pre-bleed, Pre; post prime, Bleed #1; and post boost-1, Bleed #2) with MT145K virus and a CH01-sensitive virus (Q23_17). The 3-fold diluted sera were tested against the viruses in a TZM-bl reporter cell assay.
(D) The ID50 neutralization titers of the MT145-WT and MT145K group trimer-immunized CH01 UCA HC-only KI mice sera (pre- and post-immunization bleed time points). Neutralization was assessed against the priming immunogen-matched autologous viruses in each group (MT145-WT group, MT145-WT virus; MT145K group, MT145K virus), the N160 glycan knockout variant of the MT145K virus (MT145K N160A), and a highly CH01-sensitive virus, Q23_17. The numerical values shown in the table represent the ID50 neutralization titers of the immune serum samples and were calculated by non-linear regression method from the percent neutralizations of serum titrations with virus.