scholarly journals Induction of cross-reactive antibody responses against the RBD domain of the spike protein of SARS-CoV-2 by commensal microbiota

2021 ◽  
Author(s):  
Justus Ninnemann ◽  
Lisa Budzinski ◽  
Marina Bondareva ◽  
Mario Witkowski ◽  
Stefan Angermair ◽  
...  
Keyword(s):  
Bacterial Species ◽  
Antibody Responses ◽  
Commensal Bacteria ◽  
Spike Protein ◽  
Secretory Iga ◽  
Host Proteins ◽  
Commensal Microbiota ◽  
Mucosal Surfaces ◽  
Iga Antibodies ◽  
Reactive Antibody

The commensal microflora is a source for multiple antigens that may induce cross-reactive antibodies against host proteins and pathogens. However, whether commensal bacteria can induce cross-reactive antibodies against SARS-CoV-2 remains unknown. Here we report that several commensal bacteria contribute to the generation of cross-reactive IgA antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein. We identified SARS-CoV-2 unexposed individuals with RBD-binding IgA antibodies at their mucosal surfaces. Conversely, neutralising monoclonal anti-RBD antibodies recognised distinct commensal bacterial species. Some of these bacteria, such as Streptococcus salivarius, induced a cross-reactive anti-RBD antibodies upon supplementation in mice. Conversely, severely ill COVID-19 patients showed reduction of Streptococcus and Veillonella in their oropharynx and feces and a reduction of anti-RBD IgA at mucosal surfaces. Altogether, distinct microbial species of the human microbiota can induce secretory IgA antibodies cross-reactive for the RBD of SARS-CoV-2.

scholarly journals Detection of cross-reactive IgA against SARS-CoV-2 spike 1 subunit in saliva

2021 ◽  
Author(s):  
Keiichi Tsukinoki ◽  
Tatsuo Yamamoto ◽  
Keisuke Handa ◽  
Mariko Iwamiya ◽  
Juri Saruta ◽  
...  
Keyword(s):  
Breast Milk ◽  
Recombinant Protein ◽  
University Hospital ◽  
Spike Protein ◽  
Secretory Iga ◽  
Enzyme Linked Immunosorbent Assay ◽  
Receptor Binding Domain ◽  
Blood Samples ◽  
Milk Samples ◽  
Mucosal Surfaces

AbstractAbundant secretory IgA (sIgA) in mucus, breast milk, and saliva provides immunity that prevents infection of mucosal surfaces. sIgA in pre-pandemic breast milk samples have been reported to cross-react with SARS-CoV-2, but whether it also occurs in saliva and, if so, whether it cross-reacts with SARS-CoV-2, has remained unknown. We aimed to clarify whether sIgA in saliva cross-reacts with SARS-CoV-2 spike 1 subunit in individuals who have not been infected with this virus. The study included 137 (male, n = 101; female, n = 36; mean age, 38.7 [24–65] years) of dentists and doctors in the Kanagawa Dental University Hospital. Saliva and blood samples were analyzed by PCR and immunochromatography for IgG and IgM, respectively. We then identified patients with saliva samples that were confirmed as PCR- and IgM-negative for COVID-19. Proportions of SARS-CoV-2 cross-reactive IgA-positive individuals were determined by enzyme-linked immunosorbent assay using a biotin-labeled spike S1-mFc recombinant protein covering the receptor-binding domain of SARS-CoV-2. The proportion of SARS-CoV-2 cross-reactive IgA-positive individuals was 46.7%, and this correlated negatively with age (r = −0.218, p = 0.01). The proportion of IgA-positive individuals ≥ 50 y was significantly lower than that of patients aged ≤ 49 y (p = 0.008). sIgA was purified from the saliva of all patients, and the salivary sIgA was found to suppress the binding of SARS-CoV-2 spike protein to the ACE-2 receptor. We found SARS-CoV-2 cross-reactive sIgA in the saliva of some participants who had never been infected with the virus, suggesting that sIgA helps prevent SARS-CoV-2 infection.

scholarly journals Immunoglobulin A Antibody Composition Is Sculpted to Bind the Self Gut Microbiome

2020 ◽  
Author(s):  
Chao Yang ◽  
Alice Chen-Liaw ◽  
Thomas M. Moran ◽  
Andrea Cerutti ◽  
Jeremiah J. Faith
Keyword(s):  
Bacterial Species ◽  
Immunoglobulin A ◽  
Gut Bacteria ◽  
Species Level ◽  
Commensal Bacteria ◽  
Germ Free ◽  
Serum Iga ◽  
Iga Antibodies ◽  
Gnotobiotic Mice ◽  
Species Specific

ABSTRACTDespite being the most abundantly secreted immunoglobulin isotype, the reactivity of IgA antibodies towards each individual’s own gut commensal bacteria still remains elusive. By colonizing germ-free mice with defined commensal bacteria, we found the binding specificity of bulk fecal and serum IgA towards resident gut bacteria resolves well at the species level and has modest strain level specificity. IgA hybridomas generated from lamina propria B cells of gnotobiotic mice showed that most IgA clones recognized a single bacterial species, while a small portion displayed polyreactivity. Species-specific IgAs had a range of strain specificities. Given the unique bacterial species and strain composition in each individual’s gut, our findings suggest the IgA repertoire is uniquely shaped to bind our self gut bacteria.

scholarly journals Comparison of Mucosal and Intramuscular Immunization against SARS-CoV-2 with Replication-Defective and Replicating Single-cycle Adenovirus Vaccines

2021 ◽  
Author(s):  
Michael A Barry ◽  
Haley Mudrick ◽  
Erin McGlinch ◽  
Brian Parrett ◽  
Jack Hemsath ◽  
...  
Keyword(s):  
The Body ◽  
Antibody Responses ◽  
Spike Protein ◽  
Mucosal Protection ◽  
Single Cycle ◽  
Cell Responses ◽  
Binding Domains ◽  
Mucosal Surfaces ◽  
Mucosal Vaccines ◽  
Mucosal Pathogens

SARS-CoV-2 enters the body at mucosal surfaces, such as the nose and lungs. These events involve a small number of virions at these mucosal barriers and are therefore a strategic point to stop a COVID-19 infection before it starts. Despite this, most vaccines against COVID-19 are being injected into the muscle where they will not generate the highest levels of mucosal protection. The vaccines that are approved for use in humans are all replication-defective (RD) mRNA, DNA, or adenovirus (Ad) vaccines that do not amplify antigen transgenes. We developed single cycle adenovirus (SC-Ad) vectors that replicate antigen genes up to 10,000-fold in human cells, but that are disabled from producing infectious Ad particles. We show here that SC-Ad expressing the full-length SARS-CoV-2 spike protein produces 100-fold more spike protein than a matched RD-Ad-Spike vector. When Ad-permissive hamsters were immunized with these vaccines by intranasal (IN) or intramuscular (IM) routes, SC-Ad produced significantly stronger antibody responses as compared to RD-Ad against the spike protein that rose over 14 weeks after one immunization. Single IN or IM immunizations generated significant antibody responses in serum and in bronchoalveolar lavages (BALs). IN priming, but not IM priming, generated HLA-restricted CD8 T cell responses in BALs. SC-Ad-Spike generated antibodies that retain binding to spike receptor binding domains (RBDs) with mutations from new viral variants. These data suggest empowering the genomes of gene-based vaccines with the ability to amplify antigen genes can increase potency. This may be particularly advantageous when applying mucosal vaccines to combat mucosal pathogens like SARS-CoV-2.

scholarly journals Enhanced SARS-CoV-2 Neutralization by Secretory IgA in vitro

2020 ◽  
Author(s):  
Zijun Wang ◽  
Julio C. C. Lorenzi ◽  
Frauke Muecksch ◽  
Shlomo Finkin ◽  
Charlotte Viant ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Secretory Iga ◽  
Igg Antibodies ◽  
Viral Spread ◽  
Mucosal Surfaces ◽  
Iga Response ◽  
Secretory Antibodies ◽  
Primary Form

AbstractSARS-CoV-2 primarily infects cells at mucosal surfaces. Serum neutralizing antibody responses are variable and generally low in individuals that suffer mild forms of the illness. Although potent IgG antibodies can neutralize the virus, less is known about secretory antibodies such as IgA that might impact the initial viral spread and transmissibility from the mucosa. Here we characterize the IgA response to SARS-CoV-2 in a cohort of 149 individuals. IgA responses in plasma generally correlate with IgG responses and clones of IgM, IgG and IgA producing B cells that are derived from common progenitors are evident. Plasma IgA monomers are 2-fold less potent than IgG equivalents. However, IgA dimers, the primary form in the nasopharynx, are on average 15 times more potent than IgA monomers. Thus, secretory IgA responses may be particularly valuable for protection against SARS-CoV-2 and for vaccine efficacy.

scholarly journals Antibody in Middle Ear Fluid of Children Originates Predominantly from Sera and Nasopharyngeal Secretions

2012 ◽  
Vol 19 (10) ◽  
pp. 1593-1596 ◽  
Author(s):  
Ravinder Kaur ◽  
Thomas Kim ◽  
Janet R. Casey ◽  
Michael E. Pichichero
Keyword(s):  
Middle Ear ◽  
Acute Otitis Media ◽  
Secretory Iga ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Two Dimensional Gel Electrophoresis ◽  
Middle Ear Fluid ◽  
Iga Antibodies ◽  
Iga Antibody ◽  
Entire Array

ABSTRACTThe human middle ear is devoid of any immunocompetent cells in normal mucosa. We sought to determine the source of antibody present in the middle ear of children. Total IgG, IgA, and secretory IgA antibodies were determined by enzyme-linked immunosorbent assay from the nasopharyngeal, middle ear, and serum samples of children with acute otitis media. The two-dimensional gel electrophoresis pattern of the entire array of IgA antibodies in the nasal wash (NW) and middle ear fluid (MEF) was compared from the MEF and NW samples using isoelectric focusing and Western blotting. The total IgG and IgA antibodies in the MEF and NW samples of 137 children were compared. The ratio of IgG to IgA in the MEF was significantly different (P< 0.008) compared to NW because IgA levels were higher and IgG levels lower in NW. The IgG/IgA ratio of MEF resembled serum consistent with transudation to the MEF. Small amounts of secretory IgA were detected in MEF but the electrophoresis patterns of the entire array of IgA antibodies in the MEF and NW were virtually identical in each child evaluated; thus, IgA in MEF derived predominantly from serum and the nasopharynx by reflux via the Eustachian tube. The IgG/IgA antibody levels in the MEF and the same composition of IgA antibody in the MEF and NW identifies the predominant source of antibody in the MEF as a transudate of serum combined with nasal secretions refluxed from the nasopharynx in children.

Differences in Level and Avidity of Secretory IgA Antibodies in Breast Milk of Swedish, Indian and Japanese Mothers to Soybean Protein

1991 ◽  
Vol 95 (1) ◽  
pp. 13-16 ◽  
Author(s):  
A. Morikawa ◽  
U. Dahlgren ◽  
B. Carlsson ◽  
I. Narayanan ◽  
M. Hahn-Zoric ◽  
...  
Keyword(s):  
Breast Milk ◽  
Soybean Protein ◽  
Secretory Iga ◽  
Iga Antibodies ◽  
Japanese Mothers
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