scholarly journals The immune landscape of IgA induction in the gut

2021 ◽  
Author(s):  
Claudia Seikrit ◽  
Oliver Pabst
Keyword(s):  
Protective Immunity ◽  
Immunoglobulin A ◽  
Antibody Responses ◽  
Dark Side ◽  
Secretory Immunoglobulin A ◽  
Antibody Isotype ◽  
Mucosal Antibody ◽  
Key Concepts ◽  
Basic Understanding ◽  
Secretory Immunoglobulin

AbstractAntibodies are key elements of protective immunity. In the mucosal immune system in particular, secretory immunoglobulin A (SIgA), the most abundantly produced antibody isotype, protects against infections, shields the mucosal surface from toxins and environmental factors, and regulates immune homeostasis and a peaceful coexistence with our microbiota. However, the dark side of IgA biology promotes the formation of immune complexes and provokes pathologies, e.g., IgA nephropathy (IgAN). The precise mechanisms of how IgA responses become deregulated and pathogenic in IgAN remain unresolved. Yet, as the field of microbiota research moved into the limelight, our basic understanding of IgA biology has been taking a leap forward. Here, we discuss the structure of IgA, the anatomical and cellular foundation of mucosal antibody responses, and current concepts of how we envision the interaction of SIgA and the microbiota. We center on key concepts in the field while taking account of both historic findings and exciting new observations to provide a comprehensive groundwork for the understanding of IgA biology from the perspective of a mucosal immunologist.

Different secretory immunoglobulin A antibody responses to cholera vaccination in Swedish and Pakistani women

1980 ◽  
Vol 30 (2) ◽  
pp. 427-430
Author(s):  
A M Svennerholm ◽  
L A Hanson ◽  
J Holmgren ◽  
B S Lindblad ◽  
B Nilsson ◽  
...  
Keyword(s):  
Antibody Response ◽  
Immunoglobulin A ◽  
Antibody Responses ◽  
Secretory Immunoglobulin A ◽  
Cholera Vaccine ◽  
Intestinal Immunity ◽  
Significant Difference ◽  
Pakistani Women ◽  
Cholera Vaccination ◽  
Secretory Immunoglobulin

The capacity of subcutaneous cholera vaccination to induce an antibody response in milk and saliva was studied in lactating Swedish and Pakistani women, since secretory immunoglobulin A (SIgA) antibody responses in these secretions may reflect intestinal immunity. Before immunization, most of the Pakistani women had significant titers of specific SIgA antibodies against Vibrio cholerae lipopolysaccharide in milk, whereas only a few of the Swedish women had measurable, low titers. In the Pakistani women a single subcutaneous injection of cholera vaccine gave rise to a significant SIgA titer rise in 70% of the milk and 45% of the saliva samples. The Swedish women, on the other hand, did not respond with a significant antibody response of any immunoglobulin class in milk or saliva, either after a single or after a booster dose 14 days later. In serum, however, the vaccination induced significant titer rises, mainly of IgG antibodies, also in the Swedish women, but these rises were of lower magnitude than those in the Pakistani group. The results suggest a significant difference in the capacity of parenterally administered cholera vaccine to stimulate SIgA antibody formation in naturally primed and nonprimed individuals.

scholarly journals Antigen Detection in EnteropathogenicEscherichia coli Using Secretory Immunoglobulin A Antibodies Isolated from Human Breast Milk

2000 ◽  
Vol 68 (9) ◽  
pp. 5030-5036 ◽  
Author(s):  
H. A. Manjarrez-Hernandez ◽  
S. Gavilanes-Parra ◽  
E. Chavez-Berrocal ◽  
A. Navarro-Ocaña ◽  
A. Cravioto
Keyword(s):  
Protective Immunity ◽  
Immunoglobulin A ◽  
Surface Protein ◽  
Molecular Size ◽  
Human Breast Milk ◽  
Secretory Immunoglobulin A ◽  
Protein Antigens ◽  
Infantile Diarrhea ◽  
Molecular Masses ◽  
Secretory Immunoglobulin

ABSTRACT Enteropathogenic Escherichia coli (EPEC) produces a characteristic attaching and effacing (A/E) lesion in the small intestines of infected children. The immune response to EPEC infection remains poorly characterized. The molecular targets that elicit protective immunity against EPEC disease are unknown. In this study protein antigens from EPEC were identified using secretory immunoglobulin A (sIgA) antibodies isolated from milk from Mexican women by Western blot analysis. Purified sIgA antibodies, which inhibit the adherence of EPEC to cells, reacted to many EPEC proteins, the most prominent of which were intimin (a 94-kDa outer membrane protein) and two unknown proteins with apparent molecular masses of 80 and 70 kDa. A culture supernatant protein of 110 kDa also reacted strongly with the sIgA antibodies. The molecular size of this protein and its reactivity with specific anti-EspC antiserum suggest that it is EPEC-secreted protein C (EspC). These EPEC surface protein antigens were consistently recognized by all the different sIgA samples obtained from 15 women. Screening of clinical isolates of various O serogroups from cases of severe infantile diarrhea revealed that all EPEC strains able to produce the A/E lesion showed expression of intimin and the 80- and 70-kDa proteins. Such proteins reacted strongly with the purified sIgA pool. Moreover, nonvirulent E. coli strains were unable to generate a sIgA response. The immunogenic capacities of the 80- and 70-kDa proteins as virulence antigens have not been previously reported. The strong sIgA response to intimin and the 80- and 70-kDa proteins obtained in this study indicates that such antigens stimulate intestinal immune responses and may elicit protective immunity against EPEC disease.

scholarly journals Colonisation Factor CD0873, an Attractive Oral Vaccine Candidate against Clostridioides difficile

2021 ◽  
Vol 9 (2) ◽  
pp. 306
Author(s):  
Cansu Karyal ◽  
Jaime Hughes ◽  
Michelle L. Kelly ◽  
Jeni C. Luckett ◽  
Philip V. Kaye ◽  
...  
Keyword(s):  
Pseudomembranous Colitis ◽  
Vaccine Candidate ◽  
Oral Vaccine ◽  
Immunoglobulin A ◽  
Oral Route ◽  
Hamster Model ◽  
Clostridioides Difficile ◽  
Mucosal Antibody ◽  
Gut Pathogens ◽  
Secretory Immunoglobulin

Clostridioides difficile is the main cause of health-care-associated infectious diarrhoea. Toxins, TcdA and TcdB, secreted by this bacterium damage colonic epithelial cells and in severe cases this culminates in pseudomembranous colitis, toxic megacolon and death. Vaccines in human trials have focused exclusively on the parenteral administration of toxin-based formulations. These vaccines promote toxin-neutralising serum antibodies but fail to confer protection from infection in the gut. An effective route to immunise against gut pathogens and stimulate a protective mucosal antibody response (secretory immunoglobulin A, IgA) at the infection site is the oral route. Additionally, oral immunisation generates systemic antibodies (IgG). Using this route, two different antigens were tested in the hamster model: The colonisation factor CD0873 and a TcdB fragment. Animals immunised with CD0873 generated a significantly higher titre of sIgA in intestinal fluid and IgG in serum compared to naive animals, which significantly inhibited the adherence of C. difficile to Caco-2 cells. Following challenge with a hypervirulent isolate, the CD0873-immunised group showed a mean increase of 80% in time to experimental endpoint compared to naïve animals. Survival and body condition correlated with bacterial clearance and reduced pathology in the cecum. Our findings advocate CD0873 as a promising oral vaccine candidate against C. difficile.

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