biostudies-literatureUnknown3(2)Zhang AM<h4>Background</h4>Patients with predominantly antibody deficiency (PAD) have lower anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibody levels after initial 2-dose SARS-CoV-2 vaccination than healthy controls do; however, the anti-spike antibody responses and neutralization function in patients with PAD following subsequent immunizations remain understudied.<h4>Objective</h4>We sought to characterize anti-spike antibody responses in adults with PAD over the course of 5 SARS-CoV-2 vaccine doses and identify diagnostic and immunophenotypic risk factors for low antibody response.<h4>Methods</h4>We evaluated anti-spike antibody levels in 117 adult patients with PAD and 192 adult healthy controls following a maximum of 5 SARS-CoV-2 immunizations. We assessed neutralization of the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant and analyzed infection outcomes.<h4>Results</h4>The patients with PAD had significantly lower mean anti-spike antibody levels after 3 SARS-CoV-2 vaccine doses than the healthy controls did (1,439.1 vs 21,890.4 U/mL [<i>P</i> < .0001]). Adults with secondary PAD, severe primary PAD, and high-risk immunophenotypes had lower mean anti-spike antibody levels following vaccine doses 2, 3, and/or 4 but not following vaccine dose 5. Compared with patients with mild and moderate PAD, patients with severe PAD had a higher rate of increase in anti-spike antibody levels over 5 immunizations. A strong positive correlation was observed between anti-spike antibody levels and neutralization of both the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant. Most infections were managed on an outpatient basis.<h4>Conclusions</h4>In all of the patients with PAD, anti-spike antibody levels increased with successive SARS-CoV-2 immunizations and were correlated with neutralization of both the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant. Secondary PAD, severe primary PAD, and high-risk immunophenotypes were correlated with lower mean anti-spike antibody levels following vaccine doses 2 through 4. Patients with severe PAD had the highest rate of increase in anti-spike antibody levels over 5 immunizations. These data suggest a clinical benefit to sequential SARS-CoV-2 immunizations, particularly among high-risk patients with PAD.The journal of allergy and clinical immunology. Global100234https://www.ebi.ac.uk/biostudies/studies/S-EPMC10965812biostudies-literatureSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response in adults with predominantly antibody deficiency.PMC10965812Hong JSPillai STandon MBerrios CBarmettler SBalazs ANaranbhai VDiGiacomo DVIafrate AJOng MSZhang AMYang NJZhou BFarmer JRPoznansky MCDighe ASElmoursi AfalseSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response in adults with predominantly antibody deficiency.<h4>Background</h4>Patients with predominantly antibody deficiency (PAD) have lower anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibody levels after initial 2-dose SARS-CoV-2 vaccination than healthy controls do; however, the anti-spike antibody responses and neutralization function in patients with PAD following subsequent immunizations remain understudied.<h4>Objective</h4>We sought to characterize anti-spike antibody responses in adults with PAD over the course of 5 SARS-CoV-2 vaccine doses and identify diagnostic and immunophenotypic risk factors for low antibody response.<h4>Methods</h4>We evaluated anti-spike antibody levels in 117 adult patients with PAD and 192 adult healthy controls following a maximum of 5 SARS-CoV-2 immunizations. We assessed neutralization of the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant and analyzed infection outcomes.<h4>Results</h4>The patients with PAD had significantly lower mean anti-spike antibody levels after 3 SARS-CoV-2 vaccine doses than the healthy controls did (1,439.1 vs 21,890.4 U/mL [<i>P</i> < .0001]). Adults with secondary PAD, severe primary PAD, and high-risk immunophenotypes had lower mean anti-spike antibody levels following vaccine doses 2, 3, and/or 4 but not following vaccine dose 5. Compared with patients with mild and moderate PAD, patients with severe PAD had a higher rate of increase in anti-spike antibody levels over 5 immunizations. A strong positive correlation was observed between anti-spike antibody levels and neutralization of both the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant. Most infections were managed on an outpatient basis.<h4>Conclusions</h4>In all of the patients with PAD, anti-spike antibody levels increased with successive SARS-CoV-2 immunizations and were correlated with neutralization of both the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant. Secondary PAD, severe primary PAD, and high-risk immunophenotypes were correlated with lower mean anti-spike antibody levels following vaccine doses 2 through 4. Patients with severe PAD had the highest rate of increase in anti-spike antibody levels over 5 immunizations. These data suggest a clinical benefit to sequential SARS-CoV-2 immunizations, particularly among high-risk patients with PAD.2024-01-01T00:00:00Z2024 May2025-04-04T23:52:56.543Z2025-04-04T23:52:56.543ZS-EPMC109658123854457710.1016/j.jacig.2024.100234