Characterization of the anti-spike IgG immune response to COVID-19 vaccines in people with a wide variety of immunodeficiencies

Research on COVID-19 vaccination in immune-deficient/disordered people
(IDP) has primarily focused on cancer and organ transplantation
populations. In a prospective cohort of 195 IDP and 35 healthy volunteers,
anti-spike IgG was detected in 88% of IDP post-dose 2, increasing to 93%
by six months post-dose 3. Despite high seroconversion, median IgG levels
for IDP never surpassed 1/3 that of healthy volunteers. IgG binding to
Omicron BA.1 was lower than all other variants. Angiotensin-converting
enzyme 2 pseudo-neutralization (% inhibition) was only modestly correlated
with anti-spike IgG concentration. IgG levels were not significantly
altered by participants’ use of different mRNA-based vaccines,
immunomodulating treatments, and prior SARS-CoV-2 infections. While our
data show that three doses of COVID-19 vaccinations induce anti-spike IgG
in most IDP, additional doses are needed to achieve the levels of
protection in healthy volunteers. Due to the strikingly reduced IgG
response to Omicron BA.1, the efficacy of additional vaccinations,
including bivalent vaccines, should be studied in this population.