scholarly journals A Recombinant Multivalent Vaccine (rCpa1) Induces Protection for C57BL/6 and HLA Transgenic Mice Against Pulmonary Infection with Both Species of Coccidioides

2021 ◽  
Author(s):  
Althea Campuzano ◽  
Komali Devi Pentakota ◽  
Yu-Rou Liao ◽  
Hao Zhang ◽  
Nathan P. Wiederhold ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Pulmonary Infection ◽  
Protective Efficacy ◽  
Coccidioides Immitis ◽  
Coccidioides Posadasii ◽  
Immune Correlates ◽  
Homologous Genes ◽  
Protection Activity ◽  
Induced Immunity ◽  
Human Vaccine

Coccidioidomycosis is caused by Coccidioides posadasii (Cp) and Coccidioides immitis (Ci) that have 4-5% differences in their genomic sequences. There is an urgent need to develop a human vaccine against both species. A previously created recombinant antigen (rCpa1) that contains multiple peptides derived from Cp isolate C735 is protective against the autologous isolate. The focus of this study is to evaluate cross-protective efficacy and immune correlates by the rCpa1-based vaccine against both species of Coccidioides. DNA sequence analyses of the homologous genes for the rCpa1 antigen were conducted for 39 and 17 clinical isolates of Cp and Ci, respectively. Protective efficacy and vaccine-induced immunity were evaluated for both C57BL/6 and human HLA-DR4 transgenic mice against 5 highly virulent isolates of Cp and Ci. There are a total of 7 amino acid substitutions in the rCpa1 antigen between Cp and Ci. Both C57BL/6 and HLA-DR4 mice that were vaccinated with a rCpa1 vaccine resulted in a significant reduction of fungal burden and increased numbers of IFN-γ- and IL-17-producing CD4+ T cells in the first 2 weeks post-challenge. These data support that rCpa1 has cross-protection activity against Cp and Ci pulmonary infection through activation of early Th1 and Th17 responses.

scholarly journals A Recombinant β-1,3-Glucanosyltransferase Homolog of Coccidioides posadasii Protects Mice against Coccidioidomycosis

2003 ◽  
Vol 71 (6) ◽  
pp. 3010-3019 ◽  
Author(s):  
Nelson Delgado ◽  
Jianmin Xue ◽  
Jieh-Juen Yu ◽  
Chiung-Yu Hung ◽  
Garry T. Cole
Keyword(s):  
Protective Efficacy ◽  
Respiratory Pathogen ◽  
Coccidioides Posadasii ◽  
Intranasal Route ◽  
Lethal Challenge ◽  
Valley Fever ◽  
High Sequence Homology ◽  
Parasitic Phase ◽  
Full Length Gene ◽  
Human Vaccine

ABSTRACT Coccidioides posadasii is a fungal respiratory pathogen which is responsible for recurrent epidemics of San Joaquin Valley fever (coccidioidomycosis) in desert regions of the southwestern United States. Numerous studies have revealed that the cell wall of the parasitic phase of the fungus is a reservoir of immunoreactive macromolecules and a potential source of a vaccine against this mycosis. A 495-bp fragment of a C. posadasii gene which encodes a putative wall-associated, glycosylphosphatidylinositol (GPI)-anchored β-1,3-glucanosyltransferase was identified by computational analysis of the partially sequenced genome of this pathogen. The translated, full-length gene (GEL1) showed high sequence homology to a reported β-1,3-glucanosyltransferase of Aspergillus fumigatus (70% identity, 90% similarity) and was selected for further study. The GEL1 mRNA of C. posadasii was detected at the highest level during the endosporulation stage of the parasitic cycle, and the mature protein was immunolocalized to the surface of endospores. BALB/c or C57BL/6 mice were immunized subcutaneously with the bacterium-expressed recombinant protein (rGel1p) to evaluate its protective efficacy against a lethal challenge of C. posadasii by either the intraperitoneal or intranasal route. In both cases, rGel1p-immune mice infected with the pathogen showed a significant reduction in fungal burden and increased survival compared to nonimmune mice. The recombinant β-1,3-glucanosyltransferase is a valuable addition to an arsenal of immunoreactive proteins which could be incorporated into a human vaccine against coccidioidomycosis.

scholarly journals Evaluation of Two Homologous Proline-Rich Proteins of Coccidioides posadasii as Candidate Vaccines against Coccidioidomycosis

2007 ◽  
Vol 75 (12) ◽  
pp. 5777-5787 ◽  
Author(s):  
Roger A. Herr ◽  
Chiung-Yu Hung ◽  
Garry T. Cole
Keyword(s):  
T Cell ◽  
Pulmonary Infection ◽  
Vaccine Candidate ◽  
Protective Efficacy ◽  
T Cell Epitopes ◽  
T Cell Repertoire ◽  
Coccidioides Posadasii ◽  
Cell Repertoire ◽  
Protein Sequence Identity ◽  
Combined Vaccine

ABSTRACT Evaluation of the protective efficacy of recombinant T-cell-reactive proteins of Coccidioides posadasii in a murine model of coccidioidomycosis has led to the discovery of potential vaccines against this respiratory disease. A recombinant proline-rich antigen (rAg2/Pra) has been reported to be a leading vaccine candidate. However, contradictory results exist on the protection afforded by this antigen. Subcutaneous vaccination of either C57BL/6 or BALB/c mice with rAg2/Pra plus adjuvant followed by intraperitoneal challenge with C. posadasii resulted in a significant reduction of the fungal burden at 12 to 14 days postchallenge compared to that in nonvaccinated animals. Use of the same vaccination protocol followed by intranasal (i.n.) challenge of C57BL/6 mice with an equal number of organisms culminated in chronic pulmonary infection or death over a 90-day period. Early studies of Ag2/Pra suggested that it is a component of an immunogenic complex. We reveal in this study that C. posadasii produces a homolog of the reported proline-rich antigen, designated Prp2, which shows 69% protein sequence identity and 86% similarity to Ag2/Pra. Protection against i.n. challenge of C57BL/6 mice was evaluated by vaccination with the single bacterially expressed homolog, rAg2/Pra, or rPrp2 in combination with rAg2/Pra, each in the presence of the same adjuvant. The combined vaccine provided significantly better protection than either of the single recombinant protein vaccines. Results of enzyme-linked immunospot assays of the immunized mice revealed that the two proline-rich homologs contain unique T-cell epitopes. In combination, the recombinant proteins stimulate a more heterogeneous and protective T-cell repertoire than the monovalent vaccines.

scholarly journals Combining immunoprofiling with machine learning to assess the effects of adjuvant formulation on human vaccine-induced immunity

2019 ◽  
Vol 16 (2) ◽  
pp. 400-411 ◽  
Author(s):  
Sidhartha Chaudhury ◽  
Elizabeth H. Duncan ◽  
Tanmaya Atre ◽  
Sheetij Dutta ◽  
Michele D. Spring ◽  
...  
Keyword(s):  
Machine Learning ◽  
Induced Immunity ◽  
Human Vaccine

scholarly journals Differences in Host Innate Responses among Coccidioides Isolates in a Murine Model of Pulmonary Coccidioidomycosis

2015 ◽  
Vol 14 (10) ◽  
pp. 1043-1053 ◽  
Author(s):  
Eric R. G. Lewis ◽  
Victoria R. David ◽  
Adina L. Doyle ◽  
Khadijeh Rajabi ◽  
Jeffrey A. Kiefer ◽  
...  
Keyword(s):  
Murine Model ◽  
Host Response ◽  
Early Time ◽  
Lavage Fluid ◽  
Host Responses ◽  
Coccidioides Immitis ◽  
Coccidioides Posadasii ◽  
Hybrid Strain ◽  
Susceptible Host ◽  
Content Type

ABSTRACTCoccidioides immitisandCoccidioides posadasiiare soil-dwelling fungi and the causative agents of coccidioidomycosis, a mycosis endemic to certain semiarid regions in the Americas. The most common route of infection is by inhalation of airborneCoccidioidesarthroconidia. Once a susceptible host inhales the conidia, a transition to mature endosporulated spherules can occur within the first 5 days of infection. For this study, we examined the host response in a murine model of coccidioidomycosis during a time period of infection that has not been well characterized. We collected lung tissue and bronchoalveolar lavage fluid (BALF) from BALB/c mice that were infected with aC. immitispure strain, aC. immitishybrid strain, or aC. posadasiistrain as well as uninfected mice. We compared the host responses to theCoccidioidesstrains used in this study by assessing the level of transcription of selected cytokine genes in lung tissues and characterized host and fungal proteins present in BALF. Host response varied depending on theCoccidioidesstrain that was used and did not appear to be overly robust. This study provides a foundation to begin to dissect the host immune response early in infection, to detect abundantCoccidioidesproteins, and to develop diagnostics that target these early time points of infection.

The in vivo expressed Mycobacterium tuberculosis (IVE-TB) antigen Rv2034 induces CD4+ T-cells that protect against pulmonary infection in HLA-DR transgenic mice and guinea pigs

Vaccine ◽  
2014 ◽  
Vol 32 (29) ◽  
pp. 3580-3588 ◽  
Author(s):  
Susanna Commandeur ◽  
Susan J.F. van den Eeden ◽  
Karin Dijkman ◽  
Simon O. Clark ◽  
Krista E. van Meijgaarden ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Transgenic Mice ◽  
Guinea Pigs ◽  
Cd4 T Cells ◽  
Pulmonary Infection ◽  
Hla Dr

scholarly journals PRIMARY PULMONARY COCCIDIOIDOMYCOSIS

1940 ◽  
Vol 72 (2) ◽  
pp. 167-174 ◽  
Author(s):  
Alfred E. Cronkite ◽  
Arthur R. Lack
Keyword(s):  
Weight Loss ◽  
Pulmonary Infection ◽  
Skin Tests ◽  
Coccidioides Immitis ◽  
Positive Skin ◽  
Laboratory Technique ◽  
Marked Weight

1. The literature concerning inhalation infection with Coccidioides immitis is briefly reviewed. 2. A laboratory technique for exposing animals to inhalation of the spores of Coccidioides immitis is described. 3. Primary pulmonary infection was produced in 42 per cent of 72 animals exposed by this method. 4. No marked weight loss was apparent in the animals infected. 5. Skin tests with coccidioidin were not entirely satisfactory in diagnosis. Positive skin tests with coccidioidin were obtained in many of the infected animals, but inconsistencies occurred. 6. The gross and microscopic lesions are briefly described and illustrated.

scholarly journals Development of an Aotus nancymaae Model for Shigella Vaccine Immunogenicity and Efficacy Studies

2014 ◽  
Vol 82 (5) ◽  
pp. 2027-2036 ◽  
Author(s):  
Michael Gregory ◽  
Robert W. Kaminski ◽  
Luis A. Lugo-Roman ◽  
Hugo Galvez Carrillo ◽  
Drake Hamilton Tilley ◽  
...  
Keyword(s):  
Vaccine Strain ◽  
Attack Rate ◽  
Vaccine Development ◽  
Protective Efficacy ◽  
Shigella Flexneri ◽  
Content Type ◽  
Immune Correlates ◽  
Study Results ◽  
Combination Vaccines ◽  
Series Of Experiments

ABSTRACTSeveral animal models exist to evaluate the immunogenicity and protective efficacy of candidateShigellavaccines. The two most widely used nonprimate models for vaccine development include a murine pulmonary challenge model and a guinea pig keratoconjunctivitis model. Nonhuman primate models exhibit clinical features and gross and microscopic colonic lesions that mimic those induced in human shigellosis. Challenge models for enterotoxigenicEscherichia coli(ETEC) andCampylobacterspp. have been successfully developed withAotus nancymaae, and the addition of aShigella-Aotuschallenge model would facilitate the testing of combination vaccines. A series of experiments were designed to identify the dose ofShigella flexneri2a strain 2457T that induces an attack rate of 75% in theAotusmonkey. After primary challenge, the dose required to induce an attack rate of 75% was calculated to be 1 × 1011CFU.Shigella-specific immune responses were low after primary challenge and subsequently boosted upon rechallenge. However, preexisting immunity derived from the primary challenge was insufficient to protect against the homologousShigellaserotype. A successive study inA. nancymaaeevaluated the ability of multiple oral immunizations with live-attenuatedShigellavaccine strain SC602 to protect against challenge. After three oral immunizations, animals were challenged withS. flexneri2a 2457T. A 70% attack rate was demonstrated in control animals, whereas animals immunized with vaccine strain SC602 were protected from challenge (efficacy of 80%;P= 0.05). The overall study results indicate that theShigella-Aotus nancymaaechallenge model may be a valuable tool for evaluating vaccine efficacy and investigating immune correlates of protection.

scholarly journals Coccidioidomicosis en caninos y felinos: hallazgos clínicos, diagnóstico y tratamiento

2018 ◽  
Vol 38 (1) ◽  
pp. 33-44
Author(s):  
Galo Ernesto Martínez Cepeda ◽  
Paola Revelo Ruales
Keyword(s):  
Coccidioides Immitis ◽  
Coccidioides Posadasii ◽  
Sobre Todo

La coccidioidomicosis es una enfermedad endémica de las zonas áridas de América. Se han identificado dos especies de este género, Coccidioides immitis y Coccidioides posadasii. La variedad de especies susceptibles, incluyendo a los humanos, hace que su diagnóstico tenga una gran relevancia. Esta enfermedad no presenta una sintomatología específica que facilite su identificación. Tanto en caninos como en felinos, se puede presentar como una enfermedad pulmonar leve o una enfermedad multisistémica diseminada que puede causar la muerte. El diagnóstico se basa en el hallazgo histopatológico de microabscesos (frescos) en muestras del tracto respiratorio u otros órganos con la respectiva identificación de esférulas que contengan endosporas. No obstante, a causa del desafío que representa su diagnóstico sobre todo en regiones donde no es endémica, es necesario recurrir a pruebas complementarias, como el cultivo y aislamiento, bajo las condiciones de bioseguridad adecuadas, y una posterior confirmación mediante pruebas moleculares.

scholarly journals Co-Administration of Anticancer Candidate MK-2206 Enhances the Efficacy of BCG Vaccine Against Mycobacterium tuberculosis in Mice and Guinea Pigs

2021 ◽  
Vol 12 ◽  
Author(s):  
Rania Bouzeyen ◽  
Saurabh Chugh ◽  
Tannu Priya Gosain ◽  
Mohamed-Ridha Barbouche ◽  
Meriam Haoues ◽  
...  
Keyword(s):  
T Cells ◽  
Guinea Pigs ◽  
Protective Efficacy ◽  
T Cell Response ◽  
Host Cells ◽  
Mice Model ◽  
Akt Inhibitor ◽  
Induction Of Apoptosis ◽  
Induced Immunity

The failure of M. bovis BCG to induce long-term protection has been endowed to its inability to escape the phagolysosome, leading to mild activation of CD8+ mediated T cell response. Induction of apoptosis in host cells plays an important role in potentiating dendritic cells-mediated priming of CD8+ T cells, a process defined as “cross-priming.” Moreover, IL-10 secretion by infected cells has been reported to hamper BCG-induced immunity against Tuberculosis (TB). Previously, we have reported that apoptosis of BCG-infected macrophages and inhibition of IL-10 secretion is FOXO3 dependent, a transcription factor negatively regulated by the pro-survival activated threonine kinase, Akt. We speculate that FOXO3-mediated induction of apoptosis and abrogation of IL-10 secretion along with M. bovis BCG immunization might enhance the protection imparted by BCG. Here, we have assessed whether co-administration of a known anti-cancer Akt inhibitor, MK-2206, enhances the protective efficacy of M. bovis BCG in mice model of infection. We observed that in vitro MK-2206 treatment resulted in FOXO3 activation, enhanced BCG-induced apoptosis of macrophages and inhibition of IL-10 secretion. Co-administration of M. bovis BCG along with MK-2206 also increased apoptosis of antigen-presenting cells in draining lymph nodes of immunized mice. Further, MK-2206 administration improved BCG-induced CD4+ and CD8+ effector T cells responses and its ability to induce both effector and central memory T cells. Finally, we show that co-administration of MK-2206 enhanced the protection imparted by M. bovis BCG against Mtb in aerosol infected mice and guinea pigs. Taken together, we provide evidence that MK-2206-mediated activation of FOXO3 potentiates BCG-induced immunity and imparts protection against Mtb through enhanced innate immune response.

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