Dynamics of Serum-Neutralizing Antibody Responses in Vaccinees through Multiple Doses of the BNT162b2 Vaccine.

Publication date: Nov 15, 2023

SARS-CoV-2 mRNA vaccines are administered as effective prophylactic measures for reducing virus transmission rates and disease severity. To enhance the durability of post-vaccination immunity and combat SARS-CoV-2 variants, boosters have been administered to two-dose vaccinees. However, long-term humoral responses following booster vaccination are not well characterized. A 16-member cohort of healthy SARS-CoV-2 nacEFve participants were enrolled in this study during a three-dose BNT162b2 vaccine series. Serum samples were collected from vaccinees over 420 days and screened for antigen (Ag)-specific antibody titers, IgG subclass distribution, and neutralizing antibody (nAb) responses. Vaccine boosting restored peak Ag-specific titers with sustained α-RBD IgG and IgA antibody responses when measured at six months post-boost. RBD- and spike-specific IgG4 antibody levels were markedly elevated in three-dose but not two-dose immune sera. Although strong neutralization responses were detected in two- and three-dose vaccine sera, these rapidly decayed to pre-immune levels by four and six months, respectively. While boosters enhanced serum IgG Ab reactivity and nAb responses against variant strains, all variants tested showed resistance to two- and three-dose immune sera. Our data reflect the poor durability of vaccine-induced nAb responses which are a strong predictor of protection from symptomatic SARS-CoV-2 infection. The induction of IgG4-switched humoral responses may permit extended viral persistence via the downregulation of Fc-mediated effector functions.

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Concepts Keywords
Bnt162b2 IgG4 subclass response
Downregulation neutralizing antibodies
Healthy SARS-CoV-2


Type Source Name
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pathway REACTOME SARS-CoV-2 Infection
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disease VO USA
disease VO Glycoprotein
disease VO primary vaccination
disease IDO production
disease MESH Infection
disease IDO blood
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drug DRUGBANK Coenzyme M
disease VO protocol
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drug DRUGBANK Phosphate ion
disease IDO assay
drug DRUGBANK L-Leucine
drug DRUGBANK Methylergometrine
drug DRUGBANK Amino acids
drug DRUGBANK Streptomycin
disease VO ANOVA
disease VO titer
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disease VO vaccinee
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drug DRUGBANK Esomeprazole
drug DRUGBANK Diethylstilbestrol
disease VO Viruses
disease MESH allergy
drug DRUGBANK S-Arsonocysteine
disease VO population
disease VO vaccine strain
disease IDO host
disease MESH asymptomatic infection
disease MESH coronavirus infections
disease VO vaccine efficacy
disease VO effectiveness
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drug DRUGBANK Angiotensin II
disease IDO cell
disease MESH pollen allergy
disease MESH malignancies
disease IDO pathogen
drug DRUGBANK Guanosine
drug DRUGBANK (S)-Des-Me-Ampa
disease VO vaccinated
disease MESH Breakthrough Infections
drug DRUGBANK Nonoxynol-9

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