Antibodies Generated against Conserved Antigens Expressed by Bacteria and Allergen-Bearing Fungi Suppress Airway Disease

Kin, Nicholas W.; Stefanov, Emily K.; Dizon, Brian; Kearney, John F.

doi:10.4049/jimmunol.1200702

Cited by 25 publications

(34 citation statements)

References 78 publications

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“…Exposure to particular bacterial antigens during early life can alter the numbers of these developing clones and permanently select them in to the adult repertoire (9). We have previously demonstrated that altered antigen-specific B cell responses, following neonatal immunization with bacterial vaccines containing polysaccharide or phospholipid moieties shared by Aspergillus fumigatus fungi or house dust mite (HDM), suppress allergic disease development in adult animals (15, 16). …”

Section: Introductionmentioning

confidence: 99%

Pulmonary α-1,3-Glucan–Specific IgA-Secreting B Cells Suppress the Development of Cockroach Allergy

Patel

King

Kearney

2016

The Journal of Immunology

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There is a higher incidence of allergic conditions among children living in industrialized countries than those in developing regions. One explanation for this is reduced neonatal exposure to microbes and the consequent lack of immune stimulation. Sensitivity to cockroach allergen is highly correlated with the development of severe asthma. In this study, we determined that an antibody to microbial α-1,3-glucan binds an Enterobacter species and cockroach allergen. Neonatal, but not adult, mice immunized with this α-1,3-glucan-bearing Enterobacter (MK7) are protected against cockroach allergy. Following exposure to cockroach allergen, α-1,3-glucan-specific IgA-secreting cells are present in the lungs of mice immunized with MK7 as neonates, but not in the lungs of those immunized as adults. Mice that are unable to generate anti-α-1,3-glucan IgA antibodies were immunized with MK7 as neonates and were no longer protected against cockroach allergy. Thus, neonatal, but not adult, exposure to α-1,3-glucan results in suppressed development of cockroach allergy via pulmonary α-1,3-glucan-specific IgA-secreting cells.

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Section: Introductionmentioning

confidence: 99%

Pulmonary α-1,3-Glucan–Specific IgA-Secreting B Cells Suppress the Development of Cockroach Allergy

Patel

King

Kearney

2016

The Journal of Immunology

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“…at multiple stages of its life cycle (16). In this analysis, we observed that a previously described mouse mAb, SMB19, bound to A.f.…”

Section: Resultsmentioning

confidence: 99%

“…and fluorescence microscopy. [16] This mAb has been shown previously to bind to a sialylated oligosaccharide, s-LNT associated with the capsular polysaccharide of GBSIb (12). Other mAbs to members of this streptococcal group including GBSIa (SIaE7), GBSII (SIIF5C4), GBSIII, (SIIIV18), and desialylated GBSIb (SIbD2) (described in supplementary Table 1) do not bind either A.f.…”

Section: Resultsmentioning

confidence: 99%

“…Aspergillus fumigatus (strain 13073) and isolates of Aspergillus niger (strain IMI 31274) and Aspergillus flavus (strain CBC B5107), all purchased from ATCC, were cultured on potato dextrose agar (Fisher) plates at 37°C for 5 days then harvested as described (16) in PBS, counted on a hemocytometer, and stored at 4°C. Group B streptococci, (strain names in parenthesis), GBS–Ib (H36B), GBSIa, GBSII (18RS21), and GBSIII (COH1) used in flow cytometry experiments and vaccinations were gifts from Dr. David Pritchard (UAB).…”

Section: Methodsmentioning

confidence: 99%

“…and 50μg SMB19 or control (No Ab) i.t. I.t infections were pre-formed as described in (16). Mice were monitored for survival.…”

Section: Methodsmentioning

confidence: 99%

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Antibodies Generated against Streptococci Protect in a Mouse Model of Disseminated Aspergillosis

Wharton

Stefanov

King

et al. 2015

The Journal of Immunology

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Invasive Aspergillosis (I.A.) resulting from infection by Aspergillus fumagatus (A.f.) is a leading cause of death in immunosuppressed populations. There are limited therapeutic options for this disease and currently no vaccine. There is evidence some anti-A.f. monoclonal antibodies can provide protection against I.A. However, vaccine development has been impeded by a paucity of immunological targets on this organism demonstrated to provide protective responses. Sialylated oligosaccharide epitopes found on a variety of pathogens including fungi and Group B Streptococci (GBS) are thought to be major virulence factors of these organisms facilitating pathogen attachment to host cells and modulating complement activation and phagocytosis. As some of these oligosaccharide structures are conserved across kingdoms, we screened a panel monoclonal antibodies raised against GBS serotypes for reactivity to A.f. This approach revealed that SMB19, a GBSIb type-specific mAb, reacts with A.f. conidia and hyphae. The presence of this antibody in mice, as a result of passive or active immunization, or by enforced expression of the SMB19 heavy chain as a transgene, results in significant protection in both intravenous and airway-induced models of I.A. This study demonstrates that some antibodies generated against bacterial polysaccharides engage fungal pathogens and promote their clearance in vivo and thus provide rationale of alternative strategies for the development of vaccines or therapeutic monoclonal antibodies against these organisms.

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Synthesis of a Pentasaccharide and Neoglycoconjugates Related to Fungal α‐(1→3)‐Glucan and Their Use in the Generation of Antibodies to Trace Aspergillus fumigatus Cell Wall

Komarova

Orekhova

Tsvetkov

et al. 2014

Chemistry A European J

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3-Aminopropyl α-(1→3)-pentaglucoside, a fragment of α-(1→3)-glucan of the cell wall of Aspergillus fumigatus, has been synthesized in a blockwise approach. The application of mono- and disaccharide N-phenyltrifluoroacetimidates bearing a stereodirecting 6-O-benzoyl group was essential for stereoselective α-glucosylations. In the products, p-methoxyphenyl and levulinoyl groups served as orthogonal protecting groups for the anomeric position and 3-OH group, respectively. Their removal from shared blocks led to donors and acceptors that were used for the synthesis of pentasaccharides. Coupling of free α-(1→3)-pentaglucoside with biotin and bovine serum albumin (BSA) gave glycoconjugate tools for mycological studies. Immunization of mice with the BSA conjugate induced the generation of antibodies that recognize α-(1→3)-glucan on A. fumigatus cell wall and distinguish its morphotypes. This discovery represents a first step to the development of a diagnostic test system and a vaccine to detect and fight this life-threatening pathogen.

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Antibodies Generated against Conserved Antigens Expressed by Bacteria and Allergen-Bearing Fungi Suppress Airway Disease

Cited by 25 publications

References 78 publications

Pulmonary α-1,3-Glucan–Specific IgA-Secreting B Cells Suppress the Development of Cockroach Allergy

Pulmonary α-1,3-Glucan–Specific IgA-Secreting B Cells Suppress the Development of Cockroach Allergy

Antibodies Generated against Streptococci Protect in a Mouse Model of Disseminated Aspergillosis

Synthesis of a Pentasaccharide and Neoglycoconjugates Related to Fungal α‐(1→3)‐Glucan and Their Use in the Generation of Antibodies to Trace Aspergillus fumigatus Cell Wall

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