TY - JOUR
T1 - Response to Severe Acute Respiratory Syndrome Coronavirus 2 Initial Series and Additional Dose Vaccine in Patients With Predominant Antibody Deficiency
AU - Barmettler, Sara
AU - DiGiacomo, Daniel V.
AU - Yang, Nancy J.
AU - Lam, Tiffany
AU - Naranbhai, Vivek
AU - Dighe, Anand S.
AU - Burke, Kristin E.
AU - Blumenthal, Kimberly G.
AU - Ling, Morris
AU - Hesterberg, Paul E.
AU - Saff, Rebecca R.
AU - MacLean, James
AU - Ofoman, Onosereme
AU - Berrios, Cristhian
AU - St Denis, Kerri J.
AU - Lam, Evan C.
AU - Gregory, David
AU - Iafrate, Anthony John
AU - Poznansky, Mark
AU - Lee, Hang
AU - Balazs, Alejandro
AU - Pillai, Shiv
AU - Farmer, Jocelyn R.
N1 - Funding Information:
S. Barmettler is supported by the National Institute of Allergy And Infectious Diseases of the National Institutes of Health under award no. K23AI163350. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Conflicts of interest: J.R. Farmer holds investigator-initiated grants from Bristol Myers Squibb and Pfizer with no direct relation to the work presented. The rest of the authors declare that they have no relevant conflicts of interest.
Funding Information:
S. Barmettler is supported by the National Institute of Allergy And Infectious Diseases of the National Institutes of Health under award no. K23AI163350. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2022 American Academy of Allergy, Asthma & Immunology
PY - 2022/6
Y1 - 2022/6
N2 - Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with predominant antibody deficiency (PAD) is associated with high morbidity, yet data regarding the response to SARS-CoV-2 immunization in PAD patients, including additional dose vaccine, are limited. Objective: To characterize antibody response to SARS-CoV-2 vaccine in PAD patients and define correlates of vaccine response. Methods: We assessed the levels and function of anti-SARS-CoV-2 antibodies in 62 PAD patients compared with matched healthy controls at baseline, at 4 to 6 weeks after the initial series of immunization (a single dose of Ad26.COV2.S [Janssen] or two doses of BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]), and at 4 to 6 weeks after an additional dose immunization, if received. Results: After the initial series of SARS-CoV-2 vaccination, PAD patients had lower mean anti-spike antibody levels compared with matched healthy controls (140.1 vs 547.3 U/mL; P =.02). Patients with secondary PAD (eg, B-cell depletion therapy was used) and those with severe primary PAD (eg, common variable immunodeficiency with autoinflammatory complications) had the lowest mean anti-spike antibody levels. Immune correlates of a low anti-spike antibody response included low CD4+ T helper cells, low CD19+ total B cells, and low class-switched memory (CD27+IgD/M–) B cells. In addition, a low (<100 U/mL) anti-spike antibody response was associated with prior exposure to B-cell depletion therapy, both at any time in the past (odds ratio = 5.5; confidence interval, 1.5-20.4; P =.01) and proximal to vaccination (odds ratio = 36.4; confidence interval, 1.7-791.9; P =.02). Additional dose immunization with an mRNA vaccine in a subset of 31 PAD patients increased mean anti-spike antibody levels (76.3 U/mL before to 1065 U/mL after the additional dose; P <.0001). Conclusions: Patients with secondary and severe primary PAD, characterized by low T helper cells, low B cells, and/or low class-switched memory B cells, were at risk for low antibody response to SARS-CoV-2 immunization, which improved after an additional dose vaccination in most patients.
AB - Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with predominant antibody deficiency (PAD) is associated with high morbidity, yet data regarding the response to SARS-CoV-2 immunization in PAD patients, including additional dose vaccine, are limited. Objective: To characterize antibody response to SARS-CoV-2 vaccine in PAD patients and define correlates of vaccine response. Methods: We assessed the levels and function of anti-SARS-CoV-2 antibodies in 62 PAD patients compared with matched healthy controls at baseline, at 4 to 6 weeks after the initial series of immunization (a single dose of Ad26.COV2.S [Janssen] or two doses of BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]), and at 4 to 6 weeks after an additional dose immunization, if received. Results: After the initial series of SARS-CoV-2 vaccination, PAD patients had lower mean anti-spike antibody levels compared with matched healthy controls (140.1 vs 547.3 U/mL; P =.02). Patients with secondary PAD (eg, B-cell depletion therapy was used) and those with severe primary PAD (eg, common variable immunodeficiency with autoinflammatory complications) had the lowest mean anti-spike antibody levels. Immune correlates of a low anti-spike antibody response included low CD4+ T helper cells, low CD19+ total B cells, and low class-switched memory (CD27+IgD/M–) B cells. In addition, a low (<100 U/mL) anti-spike antibody response was associated with prior exposure to B-cell depletion therapy, both at any time in the past (odds ratio = 5.5; confidence interval, 1.5-20.4; P =.01) and proximal to vaccination (odds ratio = 36.4; confidence interval, 1.7-791.9; P =.02). Additional dose immunization with an mRNA vaccine in a subset of 31 PAD patients increased mean anti-spike antibody levels (76.3 U/mL before to 1065 U/mL after the additional dose; P <.0001). Conclusions: Patients with secondary and severe primary PAD, characterized by low T helper cells, low B cells, and/or low class-switched memory B cells, were at risk for low antibody response to SARS-CoV-2 immunization, which improved after an additional dose vaccination in most patients.
KW - Additional dose
KW - Anti-nucleocapsid antibody
KW - Anti-spike antibody
KW - Common variable immunodeficiency
KW - COVID-19
KW - CVID
KW - Humoral immunodeficiency
KW - Hypogammaglobulinemia
KW - IgG subclass deficiency
KW - Neutralization assay
KW - Predominant antibody deficiency
KW - SARS-CoV-2
KW - Specific antibody deficiency
KW - Vaccine response
UR - https://www.scopus.com/pages/publications/85131904079
U2 - 10.1016/j.jaip.2022.03.017
DO - 10.1016/j.jaip.2022.03.017
M3 - Article
C2 - 35381395
AN - SCOPUS:85131904079
SN - 2213-2198
VL - 10
SP - 1622-1634.e4
JO - Journal of Allergy and Clinical Immunology: In Practice
JF - Journal of Allergy and Clinical Immunology: In Practice
IS - 6
ER -
SDG 3 Good Health and Well-being