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 Omi...