S-RBD IgG and surrogate virus neutralization by disease
category
Humoral immunogenicity outcomes including WT S-RBD IgG and WT sVNT were
analyzed at post-dose 2 and post-dose 3 timepoints by disease category
in Fig. 2A-D and listed in Table 2. Overall, 55% (18 out of 33 with
available results) and 74% (17 out of 23) patients were seropositive
(i.e., detectable S-RBD IgG) at post-dose 2 and post-dose 3
respectively. As expected, patients with humoral deficiency had the
lowest geometric mean (GM) S-RBD IgG level (Fig. 2A) and sVNT inhibition
(Fig. 2B) with 15% (2 of 13) seropositive at the post-dose 2 timepoint.
A total of 15 patients, who had X-linked severe combined
immunodeficiency (X-SCID) post-hematopoietic stem cell transplant (HSCT)
(n=1), STAT1 gain-of-function (n=1), severe congenital
neutropenia (SCN, n=1), ataxia telangiectasia (n=1), and humoral
immunodeficiencies (n=11), did not respond and were seronegative after 2
doses, suggesting these IEIs were associated with seroconversion failure
(Fig. 2A). Notably, among those with a humoral deficiency, two brothers
with X-linked agammaglobulinemia (XLA) seroconverted after dose 2. Six
more patients with CVID (n=1) and XLA (n=5) also seroconverted after
dose 3 (Fig. 2C), despite the modest level of neutralization attained
(Fig. 2D). The highest neutralization responses were observed in
patients with immune dysregulation with GM WT sVNT inhibition of 93.6%
post-dose 3 (Fig. 2D).