tetano
Editor, Senior Moderator
J Allergy Clin Immunol Glob
. 2024 Feb 20;3(2):100234.
doi: 10.1016/j.jacig.2024.100234. eCollection 2024 May. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response in adults with predominantly antibody deficiency
Anna M Zhang[SUP] 1 2 [/SUP], Ahmed Elmoursi[SUP] 3 4 [/SUP], Daniel V DiGiacomo[SUP] 3 4 [/SUP], Baijun Zhou[SUP] 3 [/SUP], Megha Tandon[SUP] 3 [/SUP], Joseph S Hong[SUP] 3 [/SUP], Nancy J Yang[SUP] 3 [/SUP], Mei-Sing Ong[SUP] 5 [/SUP], Anand S Dighe[SUP] 4 6 [/SUP], Cristhian Berrios[SUP] 6 [/SUP], Mark C Poznansky[SUP] 7 [/SUP], Anthony J Iafrate[SUP] 6 [/SUP], Vivek Naranbhai[SUP] 4 8 [/SUP], Alejandro Balazs[SUP] 9 [/SUP], Shiv Pillai[SUP] 4 9 [/SUP], Jocelyn R Farmer[SUP] 4 10 [/SUP], Sara Barmettler[SUP] 3 4 [/SUP]
Affiliations
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.
. 2024 Feb 20;3(2):100234.
doi: 10.1016/j.jacig.2024.100234. eCollection 2024 May. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response in adults with predominantly antibody deficiency
Anna M Zhang[SUP] 1 2 [/SUP], Ahmed Elmoursi[SUP] 3 4 [/SUP], Daniel V DiGiacomo[SUP] 3 4 [/SUP], Baijun Zhou[SUP] 3 [/SUP], Megha Tandon[SUP] 3 [/SUP], Joseph S Hong[SUP] 3 [/SUP], Nancy J Yang[SUP] 3 [/SUP], Mei-Sing Ong[SUP] 5 [/SUP], Anand S Dighe[SUP] 4 6 [/SUP], Cristhian Berrios[SUP] 6 [/SUP], Mark C Poznansky[SUP] 7 [/SUP], Anthony J Iafrate[SUP] 6 [/SUP], Vivek Naranbhai[SUP] 4 8 [/SUP], Alejandro Balazs[SUP] 9 [/SUP], Shiv Pillai[SUP] 4 9 [/SUP], Jocelyn R Farmer[SUP] 4 10 [/SUP], Sara Barmettler[SUP] 3 4 [/SUP]
Affiliations
- PMID: 38544577
- PMCID: PMC10965812
- DOI: 10.1016/j.jacig.2024.100234
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.