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

Anna M Zhang; Ahmed Elmoursi; Daniel V DiGiacomo; Baijun Zhou; Megha Tandon; Joseph S Hong; Nancy J Yang; Mei-Sing Ong; Anand S Dighe; Cristhian Berrios; Mark C Poznansky; Anthony J Iafrate; Vivek Naranbhai; Alejandro Balazs; Shiv Pillai; Jocelyn R Farmer; Sara Barmettler

doi:10.1016/j.jacig.2024.100234

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

J Allergy Clin Immunol Glob. 2024 Feb 20;3(2):100234. doi: 10.1016/j.jacig.2024.100234. eCollection 2024 May.

Authors

Anna M Zhang^{1

2}, Ahmed Elmoursi^{3

4}, Daniel V DiGiacomo^{3

4}, Baijun Zhou³, Megha Tandon³, Joseph S Hong³, Nancy J Yang³, Mei-Sing Ong⁵, Anand S Dighe^{4

6}, Cristhian Berrios⁶, Mark C Poznansky⁷, Anthony J Iafrate⁶, Vivek Naranbhai^{4

8}, Alejandro Balazs⁹, Shiv Pillai^{4

9}, Jocelyn R Farmer^{4

10}, Sara Barmettler^{3

4}

Affiliations

¹ Tufts Children's Hospital, Boston, Mass.
² Boston Children's Hospital, Boston, Mass.
³ Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, Mass.
⁴ Harvard Medical School, Boston, Mass.
⁵ Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Mass.
⁶ Department of Pathology, Massachusetts General Hospital, Boston, Mass.
⁷ Division of Infectious Diseases Medicine, Department of Medicine, Vaccine and Immunotherapy Center, Massachusetts General Hospital, Boston, Mass.
⁸ Dana-Farber Cancer Institute, Boston, Mass.
⁹ Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Department of Medicine, Harvard University, Cambridge, Mass.
¹⁰ Division of Allergy and Inflammation, Beth Israel Lahey Health, Harvard Medical School, Boston, Mass.

Abstract

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.

Keywords: CD19+ B cells; CD4+ T cells; Omicron BA.5 variant; Predominantly antibody deficiency; SARS-CoV-2; anti-spike antibody; class-switched memory B cells; common variable immunodeficiency; neutralization; rituximab.