Novel Strategies to Enhance Vaccine Immunity against Coccidioidomycosis

Cole, Garry T.; Hung, Chiung Yu; Sanderson, Sam D.; Hurtgen, Brady J.; Wüthrich, Marcel; Klein, Bruce S.; Deepe, George S.; Ostroff, Gary R.; Levitz, Stuart M.

doi:10.1371/journal.ppat.1003768

Cited by 31 publications

(27 citation statements)

References 24 publications

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“…Our data suggest that an adjuvant system composed of ligands to stimulate both Card9-and MyD88-mediated signals is worthy of investigation. For example, porous glucan particles that consist primarily of ␤-1,3-D-glucans and allow for carrying pathogen-specific antigens and Toll/TIR ligands, such as CpG oligonucleotides and/or IL-1, have been exploited as receptor-targeted vaccine delivery systems (53). We postulate that this glucan particle-based vaccine platform, which delivers antigens and provides adjuvanticity, can be used to induce robust Th17 and Th1 immunity to combat Coccidioides infection.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-1 Receptor but Not Toll-Like Receptor 2 Is Essential for MyD88-Dependent Th17 Immunity to Coccidioides Infection

et al. 2014

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Interleukin-17A (IL-17A)-producing CD4؉ T helper (Th17) cells have been shown to be essential for defense against pulmonary infection with Coccidioides species. However, we have just begun to identify the required pattern recognition receptors and understand the signal pathways that lead to Th17 cell activation after fungal infection. We previously reported that Card9 ؊/؊ mice vaccinated with formalin-killed spherules failed to acquire resistance to Coccidioides infection. Here, we report that both MyD88 ؊/؊ and Card9 ؊/؊ mice immunized with a live, attenuated vaccine also fail to acquire protective immunity to this respiratory disease. Like Card9 ؊/؊ mice, vaccinated MyD88 ؊/؊ mice revealed a significant reduction in numbers of both Th17 and Th1 cells in their lungs after Coccidioides infection. Both Toll-like receptor 2 (TLR2) and IL-1 receptor type 1 (IL-1r1) upstream of MyD88 have been implicated in Th17 cell differentiation. Surprisingly, vaccinated TLR2 ؊/؊ and wild-type (WT) mice showed similar outcomes after pulmonary infection with Coccidioides, while vaccinated IL-1r1 ؊/؊ mice revealed a significant reduction in the number of Th17 cells in their infected lungs compared to WT mice. Thus, activation of both IL-1r1/MyD88-and Card9-mediated Th17 immunity is essential for protection against Coccidioides infection. Our data also reveal that the numbers of Th17 cells were reduced in IL-1r1 ؊/؊ mice to a lesser extent than in MyD88 ؊/؊ mice, raising the possibility that other TLRs are involved in MyD88-dependent Th17 immunity to coccidioidomycosis. An antimicrobial action of Th17 cells is to promote early recruitment of neutrophils to infection sites. Our data revealed that neutrophils are required for vaccine immunity to this respiratory disease.

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Section: Discussionmentioning

confidence: 99%

Interleukin-1 Receptor but Not Toll-Like Receptor 2 Is Essential for MyD88-Dependent Th17 Immunity to Coccidioides Infection

et al. 2014

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“…29 Because spherules seem to promote persistence of Coccidioides, this observation suggests that specific adaptations occurred during the evolution of Coccidioides that promote survival in the face of innate and adaptive immune responses mounted by animals. 22,23,27,30,31 Innate immunity…”

Section: Overview Of Hostepathogen Interactions In CM Coccidioides Limentioning

confidence: 99%

Host–Pathogen Interactions in Coccidioidomycosis: Prognostic Clues and Opportunities for Novel Therapies

Krogstad

Johnson

Garcia-Lloret

et al. 2019

Clinical Therapeutics

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“…A successful vaccine should show protective efficacy for both immunocompetent and immunocompromised individuals [92]. Many vaccines developed to protect against coccidioidomycosis have failed to show conclusive results for various reasons, some of which we summarize below.…”

Section: Valley Fevermentioning

confidence: 99%

“…Recent research has shown that vaccines with purified plasmid DNA provide superior protection against coccidioidomycosis [92]. Currently, research is focused on pursuing a potential adjuvant vaccine designed to stimulate the appropriate level of immune response [92].…”

Section: Valley Fevermentioning

confidence: 99%