Vaccine Immunity to Coccidioidomycosis Occurs by Early Activation of Three Signal Pathways of T Helper Cell Response (Th1, Th2, and Th17)

Hung, Chiung Yu; González, Ángel; Wüthrich, Marcel; Klein, Bruce S.; Cole, Garry T.

doi:10.1128/iai.05726-11

Cited by 75 publications

(176 citation statements)

References 45 publications

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“…In the context of Dectin-1, several groups have reported the capacity of DCs to stimulate T cell-mediated immune responses (45,48) and can in addition activate Th17 cells through the secretion of IL-6 and TGF-b (14,58,59). This Th17 immune response is promoted by Dectin-1 and leads to a more efficient antifungal immunity through the recruitment of neutrophils to the infection site (13,16,(60)(61)(62).…”

Section: Discussionmentioning

confidence: 99%

Enhanced Immunogenicity of a Tricomponent Mannan Tetanus Toxoid Conjugate Vaccine Targeted to Dendritic Cells via Dectin-1 by Incorporating β-Glucan

Lipiński

Fitieh

St‐Pierre

et al. 2013

The Journal of Immunology

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In a previous attempt to generate a protective vaccine against Candida albicans, a β-mannan tetanus toxoid conjugate showed poor immunogenicity in mice. To improve the specific activation toward the fungal pathogen, we aimed to target Dectin-1, a pattern-recognition receptor expressed on monocytes, macrophages, and dendritic cells. Laminarin, a β-glucan ligand of Dectin-1, was incorporated into the original β-mannan tetanus toxoid conjugate providing a tricomponent conjugate vaccine. A macrophage cell line expressing Dectin-1 was employed to show binding and activation of Dectin-1 signal transduction pathway by the β-glucan–containing vaccine. Ligand binding to Dectin-1 resulted in the following: 1) activation of Src family kinases and Syk revealed by their recruitment and phosphorylation in the vicinity of bound conjugate and 2) translocation of NF-κB to the nucleus. Treatment of immature bone marrow–derived dendritic cells (BMDCs) with tricomponent or control vaccine confirmed that the β-glucan–containing vaccine exerted its enhanced activity by virtue of dendritic cell targeting and uptake. Immature primary cells stimulated by the tricomponent vaccine, but not the β-mannan tetanus toxoid vaccine, showed activation of BMDCs. Moreover, treated BMDCs secreted increased levels of several cytokines, including TGF-β and IL-6, which are known activators of Th17 cells. Immunization of mice with the novel type of vaccine resulted in improved immune response manifested by high titers of Ab recognizing C. albicans β-mannan Ag. Vaccine containing laminarin also affected distribution of IgG subclasses, showing that vaccine targeting to Dectin-1 receptor can benefit from augmentation and immunomodulation of the immune response.

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Section: Discussionmentioning

confidence: 99%

Enhanced Immunogenicity of a Tricomponent Mannan Tetanus Toxoid Conjugate Vaccine Targeted to Dendritic Cells via Dectin-1 by Incorporating β-Glucan

Lipiński

Fitieh

St‐Pierre

et al. 2013

The Journal of Immunology

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“…A mutation of the IL-17 receptor impairs the ability of mice to develop immunity after vaccination by a live avirulent strain of C. posadasii [64]. A patient with a STAT-3 mutation, which affect CD4 TH17 differentiation, developed coccidioidal meningitis [65,66].…”

Section: Immunologymentioning

confidence: 99%

“…are extraordinarily rare (one cannot exclude subclinical infections that boost immunity in highly endemic areas) [71]. Successful vaccination requires a T-cell mediated immune response with both TH1 and TH17 immune responses playing a role in vaccine mediated protection [64]. There is no evidence that an antibody response is protective in humans as there is no association between inherited or acquired immunoglobulin deficiencies and disseminated coccidioidomycosis, but in mouse models there is conflicting evidence about whether B cells are needed for vaccine-induced immunity [72,73].…”

Section: Vaccine Effortsmentioning

confidence: 99%

Coccidioides immitis and posadasii; A review of their biology, genomics, pathogenesis, and host immunity

Kirkland

Fierer

2018

Virulence

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Coccidioides immitis and C. posadasii are two highly pathogenic dimorphic fungal species that are endemic in the arid areas of the new world, including the region from west Texas to southern and central California in the USA that cause coccidioidomycosis (also known as Valley Fever). In highly endemic regions such as southern Arizona, up to 50% of long term residents have been infected. New information about fungal population genetics, ecology, epidemiology, and host-pathogen interactions is becoming available. However, our understanding of some aspects of coccidioidomycosis is still incomplete, including the extent of genetic variability of the fungus, the genes involved in virulence, and how the changes in gene expression during the organism’s dimorphic life cycle are related to the transformation from a free-living mold to a parasitic spherule. Unfortunately, efforts to develop an effective subunit vaccine have not yet been productive, although two potential live fungus vaccines have been developed.

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“…В качестве перспективного вакцинного препа-рата против КМ был испытан генетически скон-струированный живой аттенуированный штамм C. posadasii (̶T) [40]. Он потерял репродуктивную способность к эндоспоруляции in vivo вследствие направленной элиминации двух генов, ответствен-ных за синтез хитиназы (СТS2 и СТS3).…”

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“…Основу этой стратегии составили положения о том, что имму-нитет, обусловленный CD4+ T-клетками, являет-ся наиболее существенным для защиты; актива-ция Th1, Th2, Th17 -сигнальных путей важна для раннего протективного ответа; процессинг анти-генпрезентирующих клеток и презентация имму-нодоминантных Т-клеточных эпитопов, представ-ляющих различные стадии паразитического цикла Coccidioides spp., необходимы для формирования оптимального иммунитета [40,41]. Сконструиро-ванная рекомбинантная белковая вакцина защи-щала мышей от летальной инфекции при интрана-зальном заражении спорами гриба [43].…”

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Problems of Vaccinal Prevention of Deep Mycoses

Lipnitskii¹,

Половец²,

Антонов³

2016

Epidemiology and Vaccine Prevention

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A literature review presents date obtained during the last years about the strategy of production and protective characteristics of different experimental vaccines against opportunistic and particularly dangerous deep mycoses. The role of T-lymphocytes of Th1 and Th17 types, interactions of CD4+T - and CD8+T-cells in the immune response and maintenance of immunologic memory after immunization with vaccines against mycoses are discussed.

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Vaccine Immunity to Coccidioidomycosis Occurs by Early Activation of Three Signal Pathways of T Helper Cell Response (Th1, Th2, and Th17)

Cited by 75 publications

References 45 publications

Enhanced Immunogenicity of a Tricomponent Mannan Tetanus Toxoid Conjugate Vaccine Targeted to Dendritic Cells via Dectin-1 by Incorporating β-Glucan

Enhanced Immunogenicity of a Tricomponent Mannan Tetanus Toxoid Conjugate Vaccine Targeted to Dendritic Cells via Dectin-1 by Incorporating β-Glucan

Coccidioides immitis and posadasii; A review of their biology, genomics, pathogenesis, and host immunity

Problems of Vaccinal Prevention of Deep Mycoses

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