COVID-19 Booster Response in Patients With Predominant Antibody Deficiency

antibody proteins attack a corona virus
Immunoglobulin or antibody proteins attack a corona virus pathogen cell – 3d illustration
Researchers conducted a study to assess the effect of COVID-19 vaccination and subsequent immune responses among patients with predominant antibody deficiency.

For patients with predominant antibody deficiency (PAD), there was an increased risk for a low antibody response after SARS-CoV-2 vaccination, according to results of a study published in The Journal of Allergy and Clinical Immunology: In Practice.

For patients with PAD, infection with SARS-CoV-2 is associated with high morbidity and there is limited data on their response to SARS-CoV-2 vaccination. To address this, researchers characterized the antibody responses of these patients to vaccination with the goal of defining correlates of vaccine response.

Researchers assessed concentrations and function of anti-SARS-CoV-2 antibodies following SARS-CoV-2 vaccination among patients with PAD who were matched in a 1:1 fashion against a cohort of healthy patients (controls). Matching was performed on the basis of age and time from receipt of most recent vaccine dose. Results were compared between the groups at baseline and between 4 and 6 weeks following a single dose of the ad26.COV2.S vaccine or 2 doses of either the BNT162b2 or mRNA-1273 vaccines, as well as between 4 and 6 weeks following any additional vaccine dose.

Among patients in the PAD (n=62) and control groups (n=62), the mean age was 52.5 and 52.6 years, 69.4% and 56.5% were women, and 95.2% and 61.1% were non-Hispanic white, respectively.

Diagnosis of primary PAD was confirmed by manual chart review and a diagnosis of secondary PAD was attributed to those receiving immunosuppressive agents without the potential for discontinuation. The researchers used serologic assays to evaluate anti-spike and anti-nucleocapsid antibody concentrations, and enzyme linked immunosorbent assays (ELISA) were used for quantitative detection of total and individual isotype immunoglobulin (Ig) A, IgM, and IgG antibodies to the SARS-CoV-2 receptor binding domain.

Following SARS-CoV-2 vaccination, the researchers found that the mean concentration of anti-spike antibodies was decreased among patients in the PAD group vs those in the control group (140.1 vs 547.3 U/mL; P =.02), with mean anti-spike antibodies most decreased among patients with secondary PAD (13.4 U/mL). After adjustment for disease severity in patients with primary PAD, the mean concentration of anti-spike antibodies was most decreased among those with severe disease (35.7 U/mL), followed by those with moderate (321.8 U/mL) and mild disease (2003 U/mL).

Low anti-spike antibody responses were correlated with low CD4+ helper T cells, low CD19+ total B cells, and low class-switched memory (CD27+IgD/M-) B cells. A low anti-spike antibody response also was associated with previous exposure to B-cell depletion therapy at any time in the past (odds ratio [OR], 5.5; 95% CI, 1.5-20.4; P =.01) or proximal to vaccination (OR, 36.4; 95% CI, 1.7-791.9; P =.02).

A total of 31 (50%) patients in the PAD group were given an additional vaccine dose. Of these patients, 9.7% received an additional mRNA vaccine dose following an initial series with the Ad26.COV2.S vaccine. Following the additional vaccine dose, the overall mean concentration of anti-spike antibodies increased from 76.3 to 1065 U/mL, with a statistically significant increase observed among patients with moderate and severe primary PAD (P <.0001). Of note, 6 (19.4%) patients maintained a low antibody response (<100 U/mL) after receipt of an additional vaccine dose, with recent B-cell depletion therapy as the only persistent variable (OR, 23; 95% CI, 2.5-213.7; P =.006).

Study limitations included its single-center setting, potential confounding from immunoglobulin replacement therapy, potential sampling bias as not all patients consented to participate, and potential selection bias as this study had a retrospective design and patients were not assigned to specific types of COVID-19 vaccines. 

According to the researchers, “Given the high morbidity from COVID-19 infection in this population, strategies to improve host immunity using booster vaccination should be considered in addition to maintaining precautions regarding COVID-19 infection.”

Disclosure: One author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Barmettler S, DiGiacomo DV, Yang NJ, et al. Response to SARS-CoV-2 initial series and additional dose vaccine in patients with predominant antibody deficiency. J Allergy Clin Immunol Pract. Published online April 22, 2022. doi:10.1016/j.jaip.2022.03.017