scholarly journals Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity

2021 ◽  
Vol 17 (3) ◽  
pp. e1009324
Author(s):  
Lucas dos Santos Dias ◽  
Hannah E. Dobson ◽  
Brock Kingstad Bakke ◽  
Gregory C. Kujoth ◽  
Junfeng Huang ◽  
...  

The development of safe subunit vaccines requires adjuvants that augment immunogenicity of non-replicating protein-based antigens. Current vaccines against infectious diseases preferentially induce protective antibodies driven by adjuvants such as alum. However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). We also pinpoint the developmental steps of antigen-specific CD4+ and CD8+ T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency. Dectin-2 ligation led to successful systemic and mucosal vaccination against invasive fungal infection and Influenza A infection, respectively. O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa greatly augment vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge.

2020 ◽  
Author(s):  
Lucas Dos Santos Dias ◽  
Hannah E. Dobson ◽  
Brock Kingstad Bakke ◽  
Greg C. Kujoth ◽  
Junfeng Huang ◽  
...  

ABSTRACTThe development of safe subunit vaccines requires adjuvants that augment immunogenicity of non-replicating protein-based antigens. Current vaccines against infectious diseases preferentially induce protective antibodies driven by adjuvants such as alum. However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). We also pinpoint the developmental steps of antigen-specific CD4+ and CD8+ T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency. Dectin-2 ligation led to successful systemic and mucosal vaccination against invasive fungal infection and Influenza A infection, respectively. O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa greatly augment vaccine subunit induced protective immunity against lethal influenza and fungal pulmonary challenge.AUTHOR SUMMARYFungal disease remains a challenging clinical and public health problem in part because there is no commercial vaccine available. The lack of suitable adjuvants is a critical barrier to developing safe and effective vaccines against fungal pathogens. Current adjuvants such as alum preferentially induce antibody responses which may be limited in mediating protection against fungi. Clinical observations and animal studies implicate cellular immunity as the essential component for the resolution of fungal infections. We have recently discovered an adjuvant that augments cell mediated immune responses and vaccine induced protection against fungi. Here, we identified the structural and mechanistic requirements by which this newly discovered adjuvant induces cell mediated immunity against fungi. As a proof of principle we also demonstrate that the adjuvant drives cellular immune responses against viruses such as influenza. We anticipate that our adjuvant can be used for vaccination with safe subunit vaccines against many microbial pathogens including viruses, intracellular bacteria, fungi and parasites that require cell mediated immune responses.


Eye ◽  
2021 ◽  
Author(s):  
Ashwin Venkatesh ◽  
Ravi Patel ◽  
Simran Goyal ◽  
Timothy Rajaratnam ◽  
Anant Sharma ◽  
...  

AbstractEmerging infectious diseases (EIDs) are an increasing threat to public health on a global scale. In recent times, the most prominent outbreaks have constituted RNA viruses, spreading via droplets (COVID-19 and Influenza A H1N1), directly between humans (Ebola and Marburg), via arthropod vectors (Dengue, Zika, West Nile, Chikungunya, Crimean Congo) and zoonotically (Lassa fever, Nipah, Rift Valley fever, Hantaviruses). However, specific approved antiviral therapies and vaccine availability are scarce, and public health measures remain critical. Patients can present with a spectrum of ocular manifestations. Emerging infectious diseases should therefore be considered in the differential diagnosis of ocular inflammatory conditions in patients inhabiting or returning from endemic territories, and more general vigilance is advisable in the context of a global pandemic. Eye specialists are in a position to facilitate swift diagnosis, improve clinical outcomes, and contribute to wider public health efforts during outbreaks. This article reviews those emerging viral diseases associated with reports of ocular manifestations and summarizes details pertinent to practicing eye specialists.


Vaccine ◽  
2017 ◽  
Vol 35 (16) ◽  
pp. 2092-2099 ◽  
Author(s):  
Raquel Guiomar ◽  
Susana Pereira da Silva ◽  
Patrícia Conde ◽  
Paula Cristóvão ◽  
Ana Carina Maia ◽  
...  

1954 ◽  
Vol 52 (2) ◽  
pp. 129-150 ◽  
Author(s):  
A. L. Terzin ◽  
M. N. BordjoŠki ◽  
M. V. Milovanović ◽  
Lj. V. Stojković ◽  
M. M. Dimić

An analysis is given of the serological tests performed over a period of 15 months with viral, rickettsial and leptospiral antigens. The analysed material is made up of about 9400 tests performed on 4036 samples of serum obtained from 2430 patients and 536 animals.The incidence of the various diseases, the distribution of the positive results according to diseases, and the height of the specific titres, as well as the height of the residual titres found in the material, are discussed and analysed in detail.The procedure for the preliminary screening of the material, as well as the methods used in performing the different serological tests, are described and discussed.A few examples of possible double infections are quoted, namely atypical virus pneumonia with influenza, and influenza A with B.An analysis of the results of 1723 tests performed with influenza antigens on 909 samples of sera is presented.The results obtained from testing about 1000 sera for cold agglutinins and 482 sera for MG agglutinins are discussed in detail.Some cases of liver affections showed a marked rise in titre both of cold agglutinins and of MG agglutinins.The serum samples, numbering about 1050, drawn from normal persons or patients suffering from infections other than Q-fever, all gave titres lower than 1/64 when tested with Q-fever antigen, except the sera of four persons who were probably cases of recent inapparent infection.The geometrical mean of the titres found in sera drawn from acute Q-fever patients between the 29th and 60th days of their illness was 1/355. Of the 500 sera from various animals, 100 from sheep and eight from cows had titres of 1/8 to 1/64 against the Q-fever antigen.Thirty-four sera have been positive when tested with the soluble antigen of both the epidemic and the murine types of typhus but no serum has given a higher titre with the murine type antigen than with the epidemic type antigen. Of the thirty-four sera tested with both antigens the titres obtained with the epidemic antigen were higher than with the murine antigen in 28.The results obtained with 417 sera tested with the mumps antigen, and with the 222 sera tested with the lymphocytic choriomeningitis antigen are reported and discussed in detail.Great individual variation has been observed in the time of appearance and rise and fall of the Paul-Bunell titres. Consequently, it is advised that early and frequent blood samples should be obtained from patients who are suspected to be suffering from infectious mononucleosis. On the basis of the results of 316 Paul-Bunnell tests it is suggested that a titre of 1/20, if preceded or followed by a negative serum sample, should be taken as conclusive evidence of infectious mononucleosis.3080 human and 164 animal sera have been investigated for the presence of antibodies to various types of leptospirae. In both human and animal sera antibodies have been found most frequently against L. sejroe and L. pomona.The results of a few tests performed with toxoplasma antigen are mentioned briefly.We wish to express our gratitude to all our colleagues in Belgrade and other parts of the country who have provided us with information and additional samples of blood when requested, in particular Prof. K. Todorowich of the Infectious Diseases Hospital, Belgrade, and Drs Lj. Vuksich, M. Morelj, B. Arsich, D. Mehl and R. Papo of the Army Medical School, Belgrade.We wish to thank Dr R. Djorich of the Infectious Diseases Hospital, Belgrade, for the supply of material for testing for atypical virus pneumonia and aseptic meningitis, and Dr Ž. Perishich for help with our cases of infectious mononucleosis. Mrs Martha Milivojevich gave valuable assistance with the complement-fixation tests and with the compilation of material for this report.


2006 ◽  
Vol 51 (1) ◽  
pp. 79-86 ◽  
Author(s):  
A.C. Odebode ◽  
S.A. Jonker ◽  
C.C. Joseph ◽  
S.W. Wachira

The anti-fungal activity of schefflone, a mixture of dimmer, 3,5 dimethoxy carvacrol and annonaceous acetogenin, extracted from stem-bark and root of Uvaria scheffleri and Artabotrys bruchypetalus against Fusarium solani, Botryodiplodia theobromae, Asperillus niger and Aspergillus flavus was determined. An in-vitro bioassay showed that the minimum inhibitory effect of the compounds to the fungal pathogens occurred at 200 ppm in both radial growth and mycelia dry weight measurements. Acetogenin from A brachypetalus had a very strong anti-fungal effect on all the test fungi. The effects of the compounds were more pronounced on F solani than on the other. The bioassay methods also play a significant role in the sensitivity of the samples on the pathogens. .


2020 ◽  
Vol 40 (10) ◽  
pp. 758-775
Author(s):  
Manoela M. Piva ◽  
Claiton I. Schwertz ◽  
Ronaldo M. Bianchi ◽  
Regina T. Kemper ◽  
Luan Cleber Henker ◽  
...  

ABSTRACT: The aim of this study was to investigate the main causes of death in growing-finishing pigs in southern Brazil. During a one-year period (from 2018 to 2019), two industrial pig herds (18 and 20 thousand pigs each farm) in southern Brazil were monitored along the four seasons of the year (12 days per season on each farm), in order to perform necropsies of all pigs that died in that period. The two farms had an average monthly mortality rate ranging from 0.94 to 3.93% in the evaluated months. At necropsy, tissues were collected, fixed in 10% formalin solution and processed routinely for histopathological examination. When necessary, samples were sent for bacterial culture and PCR to identify etiologic agents. A total of 601 necropsies were performed, with 94.9% of conclusive diagnoses. Infectious diseases corresponded to 64.4% of conclusive diagnosis and non-infectious diseases to 35.6%. The most prevalent causes of death were: pneumonia (33%), gastric ulcers (15.4%), circovirosis (9.9%), systemic bacterial embolism (5.4%), polyserositis (4.4%), dilated cardiomyopathy and torsion of abdominal organs (4.3% each), and bacterial pericarditis (3.4%). Regarding pneumonias (199/601), the main agents identified in these cases were Pasteurella multocida, Influenza A virus and Mycoplasma hyopneumoniae, mainly in associations.


2019 ◽  
Vol 14 (12) ◽  
pp. 1011-1012
Author(s):  
Maurizio Sanguinetti

In this exclusive interview, Maurizio Sanguinetti discusses current issues with Candida fungal infection diagnoses, in light of its rising resistance to antifungal drugs. This interview was conducted by Ellen Colvin, Editor of Future Microbiology. Maurizio Sanguinetti, MD, is full Professor of Microbiology at the Università Cattolica del Sacro Cuore of Rome, Italy, and Director of the Institute of Microbiology and Chief of the Department of Laboratory Sciences and Infectious Diseases Sciences at the Fondazione Policlinico Agostino Gemelli IRCCS of Rome, Italy. For several years, the research activity of Maurizio Sanguinetti has mainly focused on the development of molecular methods for the rapid diagnosis of bacterial, mycobacterial and fungal infections; the elucidation of virulence and antimicrobial resistance mechanisms in clinically relevant bacterial and fungal pathogens; the characterization of the human microbiota in relationship to infectious and noninfectious diseases and implementation of new diagnostic strategies for the personalized care of patients with infectious diseases.


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