Humoral and cellular immune response to Covid-19 vaccines after primary vaccination with a 3-dose scheme and boosters vaccines in Brazilian patients with Inborn Errors of Immunity compared to healthy controls

Introduction: We investigated humoral and cellular immune responses to Covid-19 vaccines after 3-doses in Brazilian IEI patients IEI compared to healthy controls (HC).
Method: We included 55 IEI patients (13-61y) and 60 HC (13-71y) with two doses of inactivated-SARS-CoV-2 vaccine (CoronaVac) or non-replicating-viral-vectored vaccine (Oxford-AstraZeneca-ChAdOx1-nCoV-19) or mRNA vaccine (Pfizer-BioNTech-BNT162b2), followed by a 3rd-dose of Pfizer. IEI were: 27 CVID; 7 SAD; 5 AT; 4 PIK3CD; 4 Hyper-IgM-Syndrome; 4 XLA; 3 Combined-Immunodeficiency and 1 STAT-1-GOF. We evaluated T-cell responses by ELISpot and humoral response by ELISA.
Results: RBD-Wuhan neutralization was 75% in IEI (n=40) and 98% in HC (n=55) (p<0.001, t-test) 1-month after 3rd-dose (V1). 3-months after 3rd-dose (V2): 69% in IEI (n=38) and 95% in HC (n=55) (p<0.001). 1-month after 4th-dose (V3): 77% in IEI (n=33) and 98% in HC (n=33) (p=0.003). T-cell responses were comparable between groups. At V1 (IEI n=53; HC n=60), Spike positivity was 66% of IEI and 65% of HC (p=893, Chi-squared); to nucleocapsid, 47% of IEI and 36% of HC (p=0.250, Chi-squared). At V2 (IEI n=49; HC n=59), Spike positivity was 73% of IEI and 86% of HC (p=0.089); to nucleocapsid, 47% of IEI and 55% of HC (p=0.409). At V3 (IEI n=49; HC n=31), Spike positivity was 81% of IEI and 55% of HC (p=0.009); to nucleocapsid, 59% of IEI and 68% of HC (p=0.509). HC had a different statistically significant T-cell response between 1-month and 3-months after 3rd-dose to Spike (p=0.009) and to nucleocapsid (p=0.042).
Conclusions: IEI with humoral deficiency disorders responded to a 3-dose with a positive SARS-CoV-2 T-cell response, similar to HC. Antibody responses were lower in IEI.

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