Alpha-galactosylceramide enhances mucosal immunity to oral whole-cell cholera vaccines.

Abstract:

:Cholera is a severe diarrheal disease caused by the bacterium Vibrio cholerae (V. cholerae) that results in 3-4 million cases globally with 100,000-150,000 deaths reported annually. Mostly confined to developing nations, current strategies to control the spread of cholera include the provision of safe drinking water and improved sanitation and hygiene, ideally in conjunction with oral vaccination. However, difficulties associated with the costs and logistics of these strategies have hampered their widespread implementation. Specific challenges pertaining to oral cholera vaccines (OCVs) include a lack of safe and effective adjuvants to further enhance gut immune responses, the complex and costly multicomponent vaccine manufacturing, limitations of conventional liquid formulation and the lack of an integrated delivery platform. Herein we describe the use of the orally active adjuvant α-Galactosylceramide (α-GalCer) to strongly enhance intestinal bacterium- and toxin-specific IgA responses to the OCV, Dukoral® in C57BL/6 and BALB/c mice. We further demonstrate the mucosal immunogenicity of a novel multi-antigen, single-component whole-cell killed V. cholerae strain and the enhancement of its immunogenicity by adding α-GalCer. Finally, we report that combining these components and recombinant cholera toxin B subunit in the SmPill® minisphere delivery system induced strong intestinal and systemic antigen-specific antibody responses.

journal_name

Mucosal Immunol

journal_title

Mucosal immunology

authors

Davitt CJH,Longet S,Albutti A,Aversa V,Nordqvist S,Hackett B,McEntee CP,Rosa M,Coulter IS,Lebens M,Tobias J,Holmgren J,Lavelle EC

doi

10.1038/s41385-019-0159-z

subject

Has Abstract

pub_date

2019-07-01 00:00:00

pages

1055-1064

issue

4

eissn

1933-0219

issn

1935-3456

pii

10.1038/s41385-019-0159-z

journal_volume

12

pub_type

杂志文章
  • MyD88 dependence of beryllium-induced dendritic cell trafficking and CD4⁺ T-cell priming.

    abstract::Beryllium exposure results in beryllium hypersensitivity in a subset of exposed individuals, leading to granulomatous inflammation and fibrosis in the lung. In addition to its antigenic properties, beryllium has potent adjuvant activity that contributes to sensitization via unknown pathways. Here we show that berylliu...

    journal_title:Mucosal immunology

    pub_type: 杂志文章

    doi:10.1038/mi.2015.14

    authors: McKee AS,Mack DG,Crawford F,Fontenot AP

    更新日期:2015-11-01 00:00:00

  • Sphingosine-1-phosphate receptor-1 (S1P1) is expressed by lymphocytes, dendritic cells, and endothelium and modulated during inflammatory bowel disease.

    abstract::The sphingosine-1-phosphate receptor-1 (S1P1) agonist ozanimod ameliorates ulcerative colitis, yet its mechanism of action is unknown. Here, we examine the cell subsets that express S1P1 in intestine using S1P1-eGFP mice, the regulation of S1P1 expression in lymphocytes after administration of dextran sulfate sodium (...

    journal_title:Mucosal immunology

    pub_type: 杂志文章

    doi:10.1038/mi.2016.35

    authors: Karuppuchamy T,Behrens EH,González-Cabrera P,Sarkisyan G,Gima L,Boyer JD,Bamias G,Jedlicka P,Veny M,Clark D,Peach R,Scott F,Rosen H,Rivera-Nieves J

    更新日期:2017-01-01 00:00:00

  • Re-utilization of germinal centers in multiple Peyer's patches results in highly synchronized, oligoclonal, and affinity-matured gut IgA responses.

    abstract::Whereas gut IgA responses to the microbiota may be multi-centered and diverse, little is known about IgA responses to T-cell-dependent antigens following oral immunizations. Using a novel approach, gut IgA responses to oral hapten (4-hydroxy-3-nitrophenyl)acetyl-cholera toxin (NP-CT) conjugates were followed at the ce...

    journal_title:Mucosal immunology

    pub_type: 杂志文章

    doi:10.1038/mi.2012.56

    authors: Bergqvist P,Stensson A,Hazanov L,Holmberg A,Mattsson J,Mehr R,Bemark M,Lycke NY

    更新日期:2013-01-01 00:00:00

  • Neutrophils express pro- and anti-inflammatory cytokines in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques.

    abstract::Neutrophils are implicated in the pathogenesis of tuberculosis (TB), a disease caused by Mycobacterium tuberculosis infection, but the mechanisms by which they promote disease are not fully understood. Neutrophils can express cytokines that influence TB progression, and so we compared neutrophil and T-cell expression ...

    journal_title:Mucosal immunology

    pub_type: 杂志文章

    doi:10.1038/s41385-019-0195-8

    authors: Gideon HP,Phuah J,Junecko BA,Mattila JT

    更新日期:2019-11-01 00:00:00

  • Deficiency of autophagy protein Map1-LC3b mediates IL-17-dependent lung pathology during respiratory viral infection via ER stress-associated IL-1.

    abstract::While recent studies suggest that interleukin (IL)-1β production is modulated by macroautophagy or sensors of endoplasmic reticulum (ER) stress upon pro-inflammatory insult, autophagy and IL-1β production during viral infection has not been fully investigated. This was addressed using respiratory syncytial virus (RSV)...

    journal_title:Mucosal immunology

    pub_type: 杂志文章

    doi:10.1038/mi.2015.3

    authors: Reed M,Morris SH,Owczarczyk AB,Lukacs NW

    更新日期:2015-09-01 00:00:00

  • Redox signaling regulates commensal-mediated mucosal homeostasis and restitution and requires formyl peptide receptor 1.

    abstract::The mammalian gut microbiota is essential for normal intestinal development, renewal, and repair. Injury to the intestinal mucosa can occur with infection, surgical trauma, and in idiopathic inflammatory bowel disease. Repair of mucosal injury, termed restitution, as well as restoration of intestinal homeostasis invol...

    journal_title:Mucosal immunology

    pub_type: 杂志文章

    doi:10.1038/mi.2013.84

    authors: Alam A,Leoni G,Wentworth CC,Kwal JM,Wu H,Ardita CS,Swanson PA,Lambeth JD,Jones RM,Nusrat A,Neish AS

    更新日期:2014-05-01 00:00:00

  • Generation of protective pneumococcal-specific nasal resident memory CD4+ T cells via parenteral immunization.

    abstract::The generation of tissue-resident memory T cells (TRM) is an essential aspect of immunity at mucosal surfaces, and it has been suggested that preferential generation of TRM is one of the principal advantages of mucosally administered vaccines. We have previously shown that antigen-specific, IL-17-producing CD4+ T cell...

    journal_title:Mucosal immunology

    pub_type: 杂志文章

    doi:10.1038/s41385-019-0218-5

    authors: O'Hara JM,Redhu NS,Cheung E,Robertson NG,Patik I,Sayed SE,Thompson CM,Herd M,Lucas KB,Conaway E,Morton CC,Farber DL,Malley R,Horwitz BH

    更新日期:2020-01-01 00:00:00

  • Oral-gut connection: one step closer to an integrated view of the gastrointestinal tract?

    abstract::Although an enrichment of orally derived bacteria is reported in the gut microbiota of patients with several diseases, it is mostly unknown whether oral bacteria can colonize and induce intestinal inflammation. In a recent paper in Science, Atarashi et al.1 from Kenya Honda's laboratory show that a subset of orally de...

    journal_title:Mucosal immunology

    pub_type: 评论,杂志文章

    doi:10.1038/mi.2017.116

    authors: Lira-Junior R,Boström EA

    更新日期:2018-03-01 00:00:00

  • The rectal mucosa and condomless receptive anal intercourse in HIV-negative MSM: implications for HIV transmission and prevention.

    abstract::Most HIV transmissions among men who have sex with men (MSM), the group that accounted for 67% of new US infections in 2014, occur via exposure to the rectal mucosa. However, it is unclear how the act of condomless receptive anal intercourse (CRAI) may alter the mucosal immune environment in HIV-negative MSM. Here, we...

    journal_title:Mucosal immunology

    pub_type: 杂志文章

    doi:10.1038/mi.2016.97

    authors: Kelley CF,Kraft CS,de Man TJ,Duphare C,Lee HW,Yang J,Easley KA,Tharp GK,Mulligan MJ,Sullivan PS,Bosinger SE,Amara RR

    更新日期:2017-07-01 00:00:00

  • Severe viral respiratory infections: are bugs bugging?

    abstract::Viral respiratory tract infections (RTI) pose a high burden on the youngest members of our society. Several risk factors are known for severe viral respiratory disease. However, a large proportion of the severe RTI cannot be explained by these risk factors. A growing body of evidence shows that the composition of the ...

    journal_title:Mucosal immunology

    pub_type: 杂志文章,评审

    doi:10.1038/mi.2013.93

    authors: Vissers M,de Groot R,Ferwerda G

    更新日期:2014-03-01 00:00:00

  • Critical role of CXCL4 in the lung pathogenesis of influenza (H1N1) respiratory infection.

    abstract::Annual epidemics and unexpected pandemics of influenza are threats to human health. Lung immune and inflammatory responses, such as those induced by respiratory infection influenza virus, determine the outcome of pulmonary pathogenesis. Platelet-derived chemokine (C-X-C motif) ligand 4 (CXCL4) has an immunoregulatory ...

    journal_title:Mucosal immunology

    pub_type: 杂志文章

    doi:10.1038/mi.2017.1

    authors: Guo L,Feng K,Wang YC,Mei JJ,Ning RT,Zheng HW,Wang JJ,Worthen GS,Wang X,Song J,Li QH,Liu LD

    更新日期:2017-11-01 00:00:00

  • Cross-protective mucosal immunity mediated by memory Th17 cells against Streptococcus pneumoniae lung infection.

    abstract::Pneumonia caused by Streptococcus pneumoniae (Sp) remains a leading cause of serious illness and death worldwide. Immunization with conjugated pneumococcal vaccine has lowered the colonization rate and consequently invasive diseases by inducing serotype-specific antibodies. However, many of the current pneumonia cases...

    journal_title:Mucosal immunology

    pub_type: 杂志文章

    doi:10.1038/mi.2016.41

    authors: Wang Y,Jiang B,Guo Y,Li W,Tian Y,Sonnenberg GF,Weiser JN,Ni X,Shen H

    更新日期:2017-01-01 00:00:00

  • High expression of Sonic hedgehog in allergic airway epithelia contributes to goblet cell metaplasia.

    abstract::Sonic hedgehog (SHH) is abundantly expressed and critical for morphogenesis in embryonic lungs; however, SHH expression drops to a much lower level in mice from E17.5 and in humans from the 21st gestational week. We find that SHH expression is robustly upregulated in the airway epithelia of children with asthma or mou...

    journal_title:Mucosal immunology

    pub_type: 杂志文章

    doi:10.1038/s41385-018-0033-4

    authors: Xu C,Zou C,Hussain M,Shi W,Shao Y,Jiang Z,Wu X,Lu M,Wu J,Xie Q,Ke Y,Long F,Tang L,Wu X

    更新日期:2018-09-01 00:00:00

  • Periodontitis, Porphyromonas, and the pathogenesis of rheumatoid arthritis.

    abstract::Epidemiological data indicate a link between rheumatoid arthritis (RA) and periodontal disease (PD). In vitro and in vivo studies have sought to dissect potential mechanisms by which PD may contribute to initiation and progression of RA. However, these are both multifactorial, chronic diseases, and their complex etiol...

    journal_title:Mucosal immunology

    pub_type: 杂志文章,评审

    doi:10.1038/mi.2011.66

    authors: Farquharson D,Butcher JP,Culshaw S

    更新日期:2012-03-01 00:00:00

  • IL-17-mediated antifungal defense in the oral mucosa is independent of neutrophils.

    abstract::Interleukin-17 (IL-17)-mediated immunity has emerged as a crucial host defense mechanism against Candida albicans infections in mucosal tissues and the skin. The precise mechanism by which the IL-17 pathway prevents fungal outgrowth has not been clarified. Neutrophils are critical for limiting fungal dissemination and...

    journal_title:Mucosal immunology

    pub_type: 杂志文章

    doi:10.1038/mi.2014.57

    authors: Trautwein-Weidner K,Gladiator A,Nur S,Diethelm P,LeibundGut-Landmann S

    更新日期:2015-03-01 00:00:00

  • Toll-like receptor 3 in nasal CD103+ dendritic cells is involved in immunoglobulin A production.

    abstract::Intranasal inoculation with influenza hemagglutinin subunit with polyinosine-polycytidylic (polyI:C), a synthetic analog for double-stranded RNA, enhances production of vaccine-specific immunoglobulin (Ig) A, which is superior to IgG in prophylactic immunity. The mechanism whereby polyI:C skews to IgA production in th...

    journal_title:Mucosal immunology

    pub_type: 杂志文章

    doi:10.1038/mi.2017.48

    authors: Takaki H,Kure S,Oshiumi H,Sakoda Y,Suzuki T,Ainai A,Hasegawa H,Matsumoto M,Seya T

    更新日期:2018-01-01 00:00:00

  • CCR2 mediates increased susceptibility to post-H1N1 bacterial pneumonia by limiting dendritic cell induction of IL-17.

    abstract::Post influenza bacterial pneumonia is associated with significant mortality and morbidity. Dendritic cells (DCs) play a crucial role in host defense against bacterial pneumonia, but their contribution to post influenza-susceptibility to secondary bacterial pneumonia is incompletely understood. WT and CCR2-/- mice were...

    journal_title:Mucosal immunology

    pub_type: 杂志文章

    doi:10.1038/s41385-018-0106-4

    authors: Gurczynski SJ,Nathani N,Warheit-Niemi HI,Hult EM,Podsiad A,Deng J,Zemans RL,Bhan U,Moore BB

    更新日期:2019-03-01 00:00:00

  • Epithelial-mesenchymal transition in Crohn's disease.

    abstract::Crohn's disease (CD) is often accompanied by the complications of intestinal strictures and fistulas. These complications remain obstacles in CD treatment. In recent years, the importance of epithelial-mesenchymal transition in the pathogenesis of CD-associated fistulas and intestinal fibrosis has become apparent. Epi...

    journal_title:Mucosal immunology

    pub_type: 杂志文章,评审

    doi:10.1038/mi.2017.107

    authors: Jiang H,Shen J,Ran Z

    更新日期:2018-03-01 00:00:00

  • Synergistic activation of pro-inflammatory type-2 CD8+ T lymphocytes by lipid mediators in severe eosinophilic asthma.

    abstract::Human type-2 CD8+ T cells are a cell population with potentially important roles in allergic disease. We investigated this in the context of severe asthma with persistent airway eosinophilia-a phenotype associated with high exacerbation risk and responsiveness to type-2 cytokine-targeted therapies. In two independent ...

    journal_title:Mucosal immunology

    pub_type: 杂志文章

    doi:10.1038/s41385-018-0049-9

    authors: Hilvering B,Hinks TSC,Stöger L,Marchi E,Salimi M,Shrimanker R,Liu W,Chen W,Luo J,Go S,Powell T,Cane J,Thulborn S,Kurioka A,Leng T,Matthews J,Connolly C,Borg C,Bafadhel M,Willberg CB,Ramasamy A,Djukanović R,Ogg

    更新日期:2018-09-01 00:00:00

  • Tissue-specific differentiation of colonic macrophages requires TGFβ receptor-mediated signaling.

    abstract::Intestinal macrophages (mφ) form one of the largest populations of mφ in the body and are vital for the maintenance of gut homeostasis. They have several unique properties and are derived from local differentiation of classical Ly6Chi monocytes, but the factors driving this tissue-specific process are not understood. ...

    journal_title:Mucosal immunology

    pub_type: 杂志文章

    doi:10.1038/mi.2016.142

    authors: Schridde A,Bain CC,Mayer JU,Montgomery J,Pollet E,Denecke B,Milling SWF,Jenkins SJ,Dalod M,Henri S,Malissen B,Pabst O,Mcl Mowat A

    更新日期:2017-11-01 00:00:00

  • β-Glucans in food modify colonic microflora by inducing antimicrobial protein, calprotectin, in a Dectin-1-induced-IL-17F-dependent manner.

    abstract::Dectin-1 (gene symbol: Clec7a) is a receptor for β-glucans that play an important role for the host defense against fungi. Recently, we showed that Clec7a-/- mice are resistant against dextran sodium sulfate (DSS)-induced colitis because of regulatory T-cell population expansion in the colon. The regulatory T-cell exp...

    journal_title:Mucosal immunology

    pub_type: 杂志文章

    doi:10.1038/mi.2017.86

    authors: Kamiya T,Tang C,Kadoki M,Oshima K,Hattori M,Saijo S,Adachi Y,Ohno N,Iwakura Y

    更新日期:2018-05-01 00:00:00

  • Neutrophils negatively regulate induction of mucosal IgA responses after sublingual immunization.

    abstract::Induction of mucosal immunoglobulin-A (IgA) capable of providing a first line of defense against bacterial and viral pathogens remains a major goal of needle-free vaccines given via mucosal routes. Innate immune cells are known to play a central role in induction of IgA responses by mucosal vaccines, but the relative ...

    journal_title:Mucosal immunology

    pub_type: 杂志文章

    doi:10.1038/mi.2014.105

    authors: Jee J,Bonnegarde-Bernard A,Duverger A,Iwakura Y,Cormet-Boyaka E,Martin TL,Steiner HE,Bachman RC,Boyaka PN

    更新日期:2015-07-01 00:00:00

  • Immunoregulatory mechanisms of macrophage PPAR-γ in mice with experimental inflammatory bowel disease.

    abstract::Peroxisome proliferator-activated receptor-γ (PPAR-γ) is widely expressed in macrophages and has been identified as a putative target for the development of novel therapies against inflammatory bowel disease (IBD). Computational simulations identified macrophages as key targets for therapeutic interventions against IB...

    journal_title:Mucosal immunology

    pub_type: 杂志文章

    doi:10.1038/mi.2010.75

    authors: Hontecillas R,Horne WT,Climent M,Guri AJ,Evans C,Zhang Y,Sobral BW,Bassaganya-Riera J

    更新日期:2011-05-01 00:00:00

  • Free radical-producing myeloid-derived regulatory cells: potent activators and suppressors of lung inflammation and airway hyperresponsiveness.

    abstract::Levels of reactive free radicals are elevated in the airway during asthmatic exacerbations, but their roles in the pathophysiology of asthma remain unclear. We have identified subsets of myeloid-derived suppressor-like cells as key sources of nitric oxide and superoxide in the lungs of mice with evolving experimental ...

    journal_title:Mucosal immunology

    pub_type: 杂志文章

    doi:10.1038/mi.2011.16

    authors: Deshane J,Zmijewski JW,Luther R,Gaggar A,Deshane R,Lai JF,Xu X,Spell M,Estell K,Weaver CT,Abraham E,Schwiebert LM,Chaplin DD

    更新日期:2011-09-01 00:00:00

  • Mouse and human intestinal immunity: same ballpark, different players; different rules, same score.

    abstract::The study of animal immune physiology and animal models of human disease have accelerated many aspects of translational research by allowing direct, definitive investigations. In particular, the use of mice has allowed genetic manipulation, adoptive transfer, immunization, and focused cell and tissue sampling, which w...

    journal_title:Mucosal immunology

    pub_type: 杂志文章,评审

    doi:10.1038/mi.2010.85

    authors: Gibbons DL,Spencer J

    更新日期:2011-03-01 00:00:00

  • Metal-specific CD4+ T-cell responses induced by beryllium exposure in HLA-DP2 transgenic mice.

    abstract::Chronic beryllium disease (CBD) is a granulomatous lung disorder that is associated with the accumulation of beryllium (Be)-specific CD4(+) T cells into the lung. Genetic susceptibility is linked to HLA-DPB1 alleles that possess a glutamic acid at position 69 (βGlu69), and HLA-DPB1*02:01 is the most prevalent βGlu69-c...

    journal_title:Mucosal immunology

    pub_type: 杂志文章

    doi:10.1038/mi.2015.54

    authors: Falta MT,Tinega AN,Mack DG,Bowerman NA,Crawford F,Kappler JW,Pinilla C,Fontenot AP

    更新日期:2016-01-01 00:00:00

  • Distinct genital tract HIV-specific antibody profiles associated with tenofovir gel.

    abstract::The impact of topical antiretrovirals for pre-exposure prophylaxis on humoral responses following HIV infection is unknown. Using a binding antibody multiplex assay, we investigated HIV-specific IgG and IgA responses to envelope glycoproteins, p24 Gag and p66, in the genital tract (GT) and plasma following HIV acquisi...

    journal_title:Mucosal immunology

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1038/mi.2015.145

    authors: Archary D,Seaton KE,Passmore JS,Werner L,Deal A,Dunphy LJ,Arnold KB,Yates NL,Lauffenburger DA,Bergin P,Liebenberg LJ,Samsunder N,Mureithi MW,Altfeld M,Garrett N,Karim QA,Karim SA,Morris L,Tomaras GD

    更新日期:2016-05-01 00:00:00

  • The emergence of pathogenic TNF/iNOS producing dendritic cells (Tip-DCs) in a malaria model of acute respiratory distress syndrome (ARDS) is dependent on CCR4.

    abstract::Malaria-associated acute respiratory distress syndrome (MA-ARDS) and acute lung injury (ALI) are complications that cause lung damage and often leads to death. The MA-ARDS/ALI is associated with a Type 1 inflammatory response mediated by T lymphocytes and IFN-γ. Here, we used the Plasmodium berghei NK65 (PbN)-induced ...

    journal_title:Mucosal immunology

    pub_type: 杂志文章

    doi:10.1038/s41385-018-0093-5

    authors: Galvão-Filho B,de Castro JT,Figueiredo MM,Rosmaninho CG,Antonelli LRDV,Gazzinelli RT

    更新日期:2019-03-01 00:00:00

  • Thymic stromal lymphopoietin (TSLP)-mediated dermal inflammation aggravates experimental asthma.

    abstract::Individuals with one atopic disease are far more likely to develop a second. Approximately half of all atopic dermatitis (AD) patients subsequently develop asthma, particularly those with severe AD. This association, suggesting a role for AD as an entry point for subsequent allergic disease, is a phenomenon known as t...

    journal_title:Mucosal immunology

    pub_type: 杂志文章

    doi:10.1038/mi.2012.14

    authors: Han H,Xu W,Headley MB,Jessup HK,Lee KS,Omori M,Comeau MR,Marshak-Rothstein A,Ziegler SF

    更新日期:2012-05-01 00:00:00

  • Celiac disease: from oral tolerance to intestinal inflammation, autoimmunity and lymphomagenesis.

    abstract::Celiac disease is a multifactorial disorder and provides a privileged model to decipher how the interplay between environmental and genetic factors can alter mucosal tolerance to a food antigen, lead to chronic intestinal inflammation, and ultimately promote T-cell lymphomagenesis. Here we summarize how HLA-DQ2/8 mole...

    journal_title:Mucosal immunology

    pub_type: 评论,杂志文章,评审

    doi:10.1038/mi.2008.75

    authors: Meresse B,Ripoche J,Heyman M,Cerf-Bensussan N

    更新日期:2009-01-01 00:00:00