Waki, K. | Search bioRxiv

bioRxiv2023

Comprehensive analysis of nasal IgA antibodies induced by intranasal administration of the SARS-CoV-2 spike protein

Intranasal vaccination is an attractive strategy for preventing COVID-19 disease as it stimulates the production of multimeric secretory immunoglobulin A (IgA), 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, intranasal vaccine efficacy is evaluated 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 IgA induced by intranasal vaccines, we developed 99 monoclonal IgA clones from nasal mucosa and 114 monoclonal IgA or IgG clones from nonmucosal tissues of mice that were intranasally immunized with the SARS-CoV-2 spike protein. The nonmucosal IgA clones exhibited shared origins and 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 in vitro SARS-CoV-2 virus neutralization of monomeric and multimeric secretory IgA pairs recognizing different epitopes showed that even non-neutralizing monomeric IgAs, which represents 70% of the nasal IgA repertoire, can protect against SARS-CoV-2 infection when expressed as multimeric secretory IgAs. We also demonstrated that the intranasal administration of multimeric secretory IgA delivered as prophylaxis in the hamster model reduced infection-induced weight loss. Our investigation is the first to demonstrate the function of nasal IgA 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 the virus infection.

immunology↗

bioRxiv2019

A slight decrease in serum albumin level is associated with rapid progression of kidney dysfunction even within the normal range: The Yuport Health Checkup Center Cohort Study

ObjectiveA low-normal albumin level is associated with a high risk of cardiovascular disease and mortality in the general population. However, the relationship between serum albumin level and future decline of kidney function is unclear. We aimed to clarify the effect of serum albumin level on the decline of kidney function in the general population.\n\nMethodsThe data used were from 11,000 participants of a voluntary health checkup program between 1998 and 2006 conducted in Japan. The primary outcome for kidney function was a difference in estimated glomerular filtration rate ({Delta}eGFR) of [≥]3 mL/min/1.73 m2/year. The association of the risk of decreased kidney function with albumin level was determined using a logistic regression analysis. We fit separate multivariable logistic regressions for serum albumin levels (g/dL) as a continuous variable and as categorical data, classified as [≤]4.3 (n=2,530), 4.4- 4.6 (n=5,427), and [≥]4.7 (n=3,043).\n\nResultsOf 11,000 participants, 346 had a {Delta}eGFR/year of [≥]3. As compared with the participants with albumin levels of [≥]4.7 g/dL, the risk of decline in kidney function was higher not only in those with albumin levels of [≤]4.3 g/dL (adjusted OR = 2,29, 95% CI: 1.65-3.18) but also in 4.4-4.6 g/dL (adjusted OR = 1.60, 95% CI: 1.20-2.14).\n\nConclusionDecreased albumin level is an independent risk factor for rapid decline in kidney function even within the normal range.

epidemiology↗