scholarly journals A Recombinant Enolase-Montanide™ PetGel A Vaccine Promotes a Protective Th1 Immune Response against a Highly Virulent Sporothrix schenckii by Toluene Exposure

Pharmaceutics ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 144 ◽  
Author(s):  
Damiana Téllez-Martínez ◽  
Deivys Leandro Portuondo ◽  
Maria Loesch ◽  
Alexander Batista-Duharte ◽  
Iracilda Zeppone Carlos

The effect of vaccination in fungal strains that suffered changes in their virulence by exposure to environmental contaminants is largely known. Growing reports of resistance to antifungal drugs and the emergence of new highly virulent strains, possibly acquired in the environment, prompt the design of new vaccines able to prevent and combat emerging mycotic diseases. In this study, we evaluated the protective capacity of an enolase-based vaccine and Montanide PetGel A (PGA) as an adjuvant against S. schenckii with increased virulence by exposure to toluene. The adjuvanted vaccine induced a strong specific Th1 response and protective immunity against a challenge with either wildtype or toluene-adapted S. schenckii in Balb/c mice. This study highlights the role of the adjuvant PGA driving the quality of the anti-sporothrix immunity and the key component in the vaccine efficacy.

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Lukas Schuwerk ◽  
Doris Hoeltig ◽  
Karl-Heinz Waldmann ◽  
Peter Valentin-Weigand ◽  
Judith Rohde

AbstractSerotyping is the most common method to characterize field isolates of Actinobacillus (A.) pleuropneumoniae, the etiological agent of porcine pleuropneumonia. Based on serology, many farms seem to be infected and antibodies against a wide variety of serovars are detectable, but, so far it is unknown to what degree respective serovars contribute to outbreaks of clinical manifest disease. In this study, 213 German A. pleuropneumoniae field isolates retrieved for diagnostic purposes from outbreaks of porcine pleuropneumonia between 2010 and 2019 were genetically serotyped and analyzed regarding their apx-toxin gene profile using molecular methods. Serotyping revealed a prominent role of serovar 2 in clinical cases (64% of all isolates) and an increase in the detection of this serovar since 2010 in German isolates. Serovar 9/11 followed as the second most frequent serovar with about 15% of the isolates. Furthermore, very recently described serovars 16 (n = 2) and 18 (n = 8) were detected. Most isolates (93.4%) showed apx-profiles typical for the respective serovar. However, this does not hold true for isolates of serovar 18, as 75% (n = 6) of all isolates of this serovar deviated uniformly from the “typical” apx-gene profile of the reference strain 7311555. Notably, isolates from systemic lesions such as joints or meninges did not harbor the complete apxICABD operon which is considered typical for highly virulent strains. Furthermore, the extremely low occurrence (n = 1) of NAD independent (biovar II) isolates in German A. pleuropneumoniae was evident in our collection of clinical isolates.


2020 ◽  
Vol 12 (2) ◽  
pp. 3951-3956
Author(s):  
Amandeep Kaur ◽  
Kanika Bansal ◽  
Prabhu B Patil

Abstract Xanthomonas oryzae pv. oryzae (Xoo) is a serious pathogen of rice which displays tremendous interstrain variation. The emergence of highly-virulent strains of Xoo is a major threat to rice cultivation. Evolutionary insights into genome dynamics of highly virulent strains as compared with the less-virulent ones are crucial for understanding the molecular basis of exceptional success of Xoo as a highly evolved plant pathogen. In the present study, we report complete genome sequence of Xoo strains with extreme-virulent pathotypes (XVPs) characterized based on their reaction toward ten resistance (Xa) genes. One strain, IXO1088, can overcome resistance mediated by all the ten resistance genes while the other strain IXO704 cannot overcome any of them. Interestingly, our investigation revealed that XVPs display dramatic variation in the genome structure with numerous rearrangements/inversions. Moreover, XVPs also possess distinct transposon content and prophage elements that may provide genomic flux required for the acquisition of novel gene cassettes and structural changes in the genome. Interestingly, analysis of transcription activator-like effector proteins, which are major virulence determinants of Xanthomonas pathogen show marked variation in the transcription activator-like effector content and DNA binding domain of tal genes. Overall, the present study indicates the possible role of mobilomes and repetitive elements in major structural and sequence alterations, which may be leading to the emergence of novel and extreme pathotypes. The knowledge and resource of XVPs will be invaluable in the further systematic understanding of evolution and management of variant pathotypes of Xoo.


2010 ◽  
Vol 207 (7) ◽  
pp. 1421-1433 ◽  
Author(s):  
Patricia A. Darrah ◽  
Sonia T. Hegde ◽  
Dipti T. Patel ◽  
Ross W. B. Lindsay ◽  
Linda Chen ◽  
...  

The quality of a Th1 response can be a prospective correlate of vaccine-mediated protection against certain intracellular pathogens. Using two distinct vaccine platforms, we evaluate the influence of interleukin (IL) 10 production on the magnitude, quality, and protective capacity of CD4+ T cell responses in the mouse model of Leishmania major infection. Multiparameter flow cytometry was used to delineate the CD4+ T cell production of interferon (IFN) γ, IL-2, tumor necrosis factor (TNF), and IL-10 (or combinations thereof) after vaccination. Immunization with a high dose of adenovirus (ADV) expressing leishmanial proteins (MML-ADV) elicited a limited proportion of multifunctional IFN-γ+IL-2+TNF+ Th1 cells, a high frequency of IL-10–producing CD4+ T cells, and did not protect against subsequent challenge. Surprisingly, in the absence of IL-10, there was no change in the magnitude, quality, or protective capacity of the Th1 response elicited by high-dose MML-ADV. In contrast, after immunization with MML protein and CpG (MML + CpG), IL-10 limited the production of IL-12 by DCs in vivo, thereby decreasing the generation of multifunctional Th1 cells. Consequently, three immunizations with MML + CpG were required for full protection. However, inhibiting IL-10 at the time of immunization enhanced the magnitude and quality of the Th1 response sufficiently to mediate protection after only a single immunization. Overall, we delineate distinct mechanisms by which vaccines elicit protective Th1 responses and underscore the importance of multifunctional CD4+ T cells.


2009 ◽  
Vol 77 (7) ◽  
pp. 2824-2831 ◽  
Author(s):  
Florian Gehre ◽  
Radek Spisek ◽  
Arun S. Kharat ◽  
Phillip Matthews ◽  
Anjli Kukreja ◽  
...  

ABSTRACT In recent reports it was shown that genetically modified choline-free strains of Streptococcus pneumoniae (D39Cho−licA64 and D39ChiplicB31) expressing the type II capsular polysaccharide were virtually avirulent in the murine sepsis model, in sharp contrast to the isogenic and highly virulent strains D39Cho− and D39Chip, which have retained the choline residues at their surface. We now demonstrate that this choline-associated virulence is independent of Toll-like receptor 2 recognition. Also, despite the lack of virulence, choline-free strains of S. pneumoniae were able to activate splenic dendritic cells, induce secretion of proinflammatory cytokines, and produce specific protective immunity against subsequent challenge. However, after this transient engagement of the immune system the choline-free bacteria were rapidly cleared from the blood, while the isogenic virulent strain D39Cho− continued to grow, accompanied by prolonged expression of cytokines, eventually killing the experimental animals. The critical contribution of choline residues to the virulence potential of pneumococci appears to be the role that these amino alcohol residues play in a pneumococcal immune evasion strategy, the mechanism of which is unknown at the present time.


1974 ◽  
Vol 20 (10) ◽  
pp. 1417-1422
Author(s):  
K. Taubchi ◽  
H. Sato ◽  
B. B. Diena

We have investigated the protective capacity and cytotoxicity of filtrates (CF), dialysates (DL), and dialyzed filtrates (DCF) from two highly virulent and two moderately virulent strains of Pseudomonas aeruginosa. Most of the protective ability of the CF was found in the DCF, while the low molecular weight material in the DL was responsible for most of the cytotoxicity of CF. This suggests the possible purification of our culture filtrates (CF) by eliminating the low molecular weight dialyzable material. There was a significant difference in the amount of protein in the DL from the highly virulent strains as compared with DL from strains of lesser virulence. CF and DCF but not DL reacted in an agar gel system against homologous and heterologous CF antisera.


1999 ◽  
Vol 67 (2) ◽  
pp. 546-553 ◽  
Author(s):  
Bertrand Picard ◽  
José Sevali Garcia ◽  
Stéphanie Gouriou ◽  
Patrick Duriez ◽  
Naïma Brahimi ◽  
...  

ABSTRACT Previous studies suggesting a link between Escherichia coli phylogenetic groups and extraintestinal virulence have been hampered by the difficulty in establishing the intrinsic virulence of a bacterial strain. Indeed, unidentified virulence factors do exist, and the susceptibility of the host to infection is highly variable. To overcome these difficulties, we have developed a mouse model of extraintestinal virulence to test the virulence of the strains under normalized conditions. We then assessed the phylogenetic relationships compared to the E. coli reference (ECOR) collection, the presence of several known virulence determinants, and the lethality to mice of 82 human adult E. coli strains isolated from normal feces and during the course of extraintestinal infections. Commensal strains belong mainly to phylogenetic groups A and B1, are devoid of virulence determinants, and do not kill the mice. Strains exhibiting the same characteristics as the commensal strains can be isolated under pathogenic conditions, thus indicating the role of host-dependent factors, such as susceptibility linked to underlying disease, in the development of infection. Some strains of phylogenetic groups A, B1, and D are able to kill the mice, their virulence being most often correlated with the presence of virulence determinants. Lastly, strains of the B2 phylogenetic group represent a divergent lineage of highly virulent strains which kill the mice at high frequency and possess the highest level of virulence determinants. The observed link between virulence and phylogeny could correspond to the necessity of virulence determinants in a genetic background that is adequate for the emergence of a virulent clone, an expression of the interdependency of pathogenicity and metabolic activities in pathogenic bacteria.


2013 ◽  
Vol 21 (1) ◽  
pp. 24-33 ◽  
Author(s):  
Anne Eschen ◽  
Franzisca Zehnder ◽  
Mike Martin

This article introduces Cognitive Health Counseling 40+ (CH.CO40+), an individualized intervention that is conceptually based on the orchestration model of quality-of-life management ( Martin & Kliegel, 2010 ) and aims at improving satisfaction with cognitive health in adults aged 40 years and older. We describe the theoretically deduced characteristics of CH.CO40+, its target group, its multifactorial nature, its individualization, the application of subjective and objective measures, the role of participants as agents of change, and the rationale for choosing participants’ satisfaction with their cognitive health as main outcome variable. A pilot phase with 15 middle-aged and six older adults suggests that CH.CO40+ attracts, and may be particularly suitable for, subjective memory complainers. Implications of the pilot data for the further development of the intervention are discussed.


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