Breakthrough infection (BI) after coronavirus disease 2019 (COVID-19) vaccination has exploded owing to the emergence of various SARS-CoV-2 variants and has become a major problem at present. In this study, we analyzed the epidemiological information and possession status of neutralizing antibodies in patients with BI using SARS-CoV-2 pseudotyped viruses (SARS-CoV-2pv). Analysis of 44 specimens diagnosed with COVID-19 after two or more vaccinations showed high inhibition of infection by 90% or more against the Wuhan strain and the Alpha and Delta
Intranasal vaccination is an attractive strategy for preventing COVID-19 disease as it stimulates the production of multimeric secretory immunoglobulin A (IgAs), the predominant antibody isotype in the mucosal immune system, at the target site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry. Currently, the evaluation of intranasal vaccine efficacy is based on the measurement of polyclonal antibody titers in nasal lavage fluid. However, how individual multimeric secretory IgA protects the mucosa from SARS-CoV-2 infection remains to be elucidated. To understand the precise contribution and molecular nature of multimeric secretory IgAs induced by intranasal vaccines, we developed 99 monoclonal IgAs from nasal mucosa and 114 monoclonal IgAs or IgGs from nonmucosal tissues of mice that were intranasally immunized with the SARS-CoV-2 spike protein. The nonmucosal IgAs exhibited shared origins and both common and unique somatic mutations with the related nasal IgA clones, indicating that the antigen-specific plasma cells in the nonmucosal tissues originated from B cells stimulated at the nasal mucosa. Comparing the spike protein binding reactivity, angiotensin-converting enzyme-2-blocking and SARS-CoV-2 virus neutralization of monomeric and multimeric IgA pairs recognizing different epitopes showed that even nonneutralizing monomeric IgA, which represents 70% of the nasal IgA repertoire, can protect against SARS-CoV-2 infection when expressed as multimeric secretory IgAs. Our investigation is the first to demonstrate the function of nasal IgAs at the monoclonal level, showing that nasal immunization can provide effective immunity against SARS-CoV-2 by inducing multimeric secretory IgAs at the target site of virus infection.
BackgroundsThis study analysed secondary attack rates (SARs), comparing alpha variants, delta variants and non-variants of concern (non-VOCs), using clinical and close-contact tracing data.MethodsWe analysed coronavirus disease 2019 (COVID-19) case data from a database and contact tracing data between July and October 2020 (Cohort 1) and April 2021 (Cohort 2) and between July and August 2021 (Cohort 3) in a city in Toyama prefecture, Japan. Real-time polymerase chain reaction (PCR) was used to detect the N501Y (alpha variant) and L452R (delta variant) mutations. We calculated the SARs considering close contact, index case and contact setting characteristics. Relative risks (RRs) of secondary attack were analysed using Poisson regression models.ResultsAmong 123 index cases and 530 close contacts in Cohort 1, 246 index cases and 988 close contacts in Cohort 2, and 304 index cases and 984 close contacts in Cohort 3, the SARs associated with alpha and delta variant index cases were 1.47 times and 1.89 times higher than those associated with non-VOC index cases. Delta variant index cases were associated with the highest SAR (29.2%) in the same household and a 2.40-fold (95% CI: 1.62-3.56) higher risk of transmission than non-VOC index cases. The age and symptoms of index cases were associated with the SAR.ConclusionsWe confirmed that VOC index cases were associated with increased transmissibility. Population longitudinal surveillance data linked with contact-tracing data provide valuable information for elucidation of the characteristics of newly emerging variants.
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