Journal of Allergy and Clinical Immunology: Global (May 2024)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response in adults with predominantly antibody deficiency

  • Anna M. Zhang, MD,
  • Ahmed Elmoursi, MD, MPH,
  • Daniel V. DiGiacomo, MD, MPH,
  • Baijun Zhou, MHS,
  • Megha Tandon, BA,
  • Joseph S. Hong, BS,
  • Nancy J. Yang, BS,
  • Mei-Sing Ong, PhD,
  • Anand S. Dighe, MD, PhD,
  • Cristhian Berrios, MD,
  • Mark C. Poznansky, MD, PhD,
  • Anthony J. Iafrate, MD, PhD,
  • Vivek Naranbhai, PhD, MB, ChB,
  • Alejandro Balazs, PhD,
  • Shiv Pillai, MBBS, PhD,
  • Jocelyn R. Farmer, MD, PhD,
  • Sara Barmettler, MD

Journal volume & issue
Vol. 3, no. 2
p. 100234

Abstract

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Background: 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. Objective: 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. Methods: 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. Results: 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 [P < .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. Conclusions: 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.

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