AZD1222-induced nasal antibody responses are shaped by prior SARS-CoV-2 infection and correlate with virologic outcomes in breakthrough infection

• Published in: Cell reports. Medicine 2023-01, Vol.4 (1), p.100882, Article 100882
• Main Authors: Aksyuk, Anastasia A., Bansal, Himanshu, Wilkins, Deidre, Stanley, Ann Marie, Sproule, Stephanie, Maaske, Jill, Sanikommui, Satya, Hartman, William R., Sobieszczyk, Magdalena E., Falsey, Ann R., Kelly, Elizabeth J.
• Format: Article
• Language: English
• Subjects: Antibody Formation; AZD1222; breakthrough infection; Breakthrough Infections; ChAdOx1 nCoV-19; Clinical Trials, Phase III as Topic; COVID-19; COVID-19 vaccine; Double-Blind Method; Humans; immunoassay; Immunoglobulin A; Immunoglobulin G; mucosal immune response; nasal antibody; Nasal Mucosa; nasal mucosal immunity; SARS-CoV-2; SARS-CoV-2 spike antibodies; serology
• ISSN: 2666-3791; 2666-3791
• DOI: 10.1016/j.xcrm.2022.100882

The nasal mucosa is an important initial site of host defense against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, intramuscularly administered vaccines typically do not achieve high antibody titers in the nasal mucosa. We measure anti-SARS-CoV-2 spike immunoglobulin G (IgG) and IgA in nasal epithelial lining fluid (NELF) following intramuscular vaccination of 3,058 participants from the immunogenicity substudy of a phase 3, double-blind, placebo-controlled study of AZD1222 vaccination (ClinicalTrials.gov: NCT04516746). IgG is detected in NELF collected 14 days following the first AZD1222 vaccination. IgG levels increase with a second vaccination and exceed pre-existing levels in baseline-SARS-CoV-2-seropositive participants. Nasal IgG responses are durable and display strong correlations with serum IgG, suggesting serum-to-NELF transudation. AZD1222 induces short-lived increases to pre-existing nasal IgA levels in baseline-seropositive vaccinees. Vaccinees display a robust recall IgG response upon breakthrough infection, with overall magnitudes unaffected by time between vaccination and illness. Mucosal responses correlate with reduced viral loads and shorter durations of viral shedding in saliva. [Display omitted] •Anti-spike IgG is detected in nasal mucosa after intramuscular AZD1222 vaccination•Nasal IgG correlated with serum IgG levels and showed durability through 1 year•AZD1222 boosted existing anti-spike nasal IgA levels in seropositive individuals•Nasal IgG levels correlated with reduced viral load and shedding duration in saliva The nasal mucosa represents an important initial line of host defense against SARS-CoV-2. Aksyuk et al. describe anti-SARS-CoV-2 spike IgG and IgA responses in the nasal mucosa following intramuscular vaccination and upon breakthrough SARS-CoV-2 infection in participants from a phase 3, double-blind, placebo-controlled study of AZD1222 (ChAdOx1 nCoV-19) vaccination (ClinicalTrials.gov: NCT04516746).