Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine Response in Adults with Predominantly Antibody Deficiency

Background Patients with predominantly antibody deficiency (PAD) have lower anti-SARS-CoV-2 spike antibody levels after initial two-dose SARS-CoV-2 vaccination as compared to healthy controls; however, anti-spike antibody responses and neutralization function in PAD patients following subsequent immunizations remain understudied. Objective We sought to characterize anti-spike antibody responses in adults with PAD over five SARS-CoV-2 vaccine doses and identify diagnostic and immunophenotypic risk factors for low antibody response. Methods We evaluated anti-spike antibody levels in 117 adult PAD patients and 192 adult healthy controls following a maximum of five SARS-CoV-2 immunizations. We assessed neutralization of the SARS-CoV-2 wild-type strain and Omicron BA.5 variant and analyzed infection outcomes. Results PAD patients had significantly lower mean anti-spike antibody levels after three SARS-CoV-2 vaccine doses compared to healthy controls (1,439.1 versus 21,890.4 U/mL; p<0.0001). Adults with secondary PAD, severe primary PAD, and high-risk immunophenotypes had lower mean anti-spike antibody levels following vaccine doses two, three, and/or four, but not following vaccine dose five. Compared to patients with mild and moderate PAD, patients with severe PAD had a higher rate of increase in anti-spike antibody levels over five immunizations. A strong positive correlation was observed between anti-spike antibody levels and neutralization of both SARS-CoV-2 wild-type strain and Omicron BA.5 variant. Most infections were managed outpatient. Conclusions Anti-spike antibodies in all PAD patients increased with successive SARS-CoV-2 immunizations and 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 correlated with lower mean anti-spike antibody levels following vaccine doses two through four. Severe PAD patients had the highest rate of increase in anti-spike antibody levels over five immunizations. These data suggest a clinical benefit to sequential SARS-CoV-2 immunizations, particularly among high-risk PAD patients.