­­­­­COVID-19 vaccination responses with different vaccine platforms in patients with inborn errors of immunity

Abstract

Patients with Inborn Errors of Immunity (IEI) in Argentina were encouraged to receive licensed Sputnik, AstraZeneca, Sinopharm, Moderna, and Pfizer vaccines, even though most of the data on available vaccines comes from trials conducted in healthy individuals. We aimed to evaluate the safety and immunogenicity of the different vaccines in IEI patients in Argentina. The study cohort included adults and pediatric IEI patients (n=118) and age-matched healthy-controls (HC) (n=37). Samples were collected before, 28+/-3 days after the first and the second dose of the vaccine. B-cell response was evaluated by measuring IgG anti-Spike(S)/ receptor binding domain (RBD) and anti-nucleocapsid(N) antibodies by ELISA. Neutralization antibodies were also assessed with an alpha-S protein-expressing pseudo-virus assay. The T-cell response was analyzed by IFN-γ secretion on S or N-stimulated PBMC by ELISPOT and the frequency of S-specific circulating T follicular-helper cells (TFH) was evaluated by flow cytometry. No moderate/severe vaccine-associated adverse events were observed. Regarding the antibody response, anti-S/RBD titers showed significant differences in both pediatric and adult IEI patients versus the age-matched HC cohort (p<0.05). Neutralizing antibodies were detected in 71/99 patients and were also significantly lower in the patient cohort than age-matched HC (p<0.01). Positive S-specific IFN-γ response was observed in 84.5% of IEI patients and 82.1% presented S-specific TFH cells. In conclusion, COVID-19 vaccines showed safety in IEI patients and, although immunogenicity was lower than HC, they showed specific anti-S/RBD IgG, neutralizing antibody titers and T-cell-dependent cellular immunity with IFN-γ secreting T-cells. These findings may guide the recommendation of vaccination in IEI patients to prevent COVID-19 disease .