- Does structurally-mature dengue virion matter in vaccine preparation in post-Dengvaxia era? [Journal Article]
- HVHum Vaccin Immunother 2019 Jul 17
- The unexpectedly low vaccine efficacy of Dengvaxia®, developed by Sanofi Pasteur, and a higher risk of severe diseases after vaccination among dengue naïve children or children younger than 6 years o…
The unexpectedly low vaccine efficacy of Dengvaxia®, developed by Sanofi Pasteur, and a higher risk of severe diseases after vaccination among dengue naïve children or children younger than 6 years old, have cast skepticism about the safety of dengue vaccination resulting in the suspension of school-based immunization programs in the Philippines. The absence of immune correlates of protection from dengue virus (DENV) infection hampers the development of other potential DENV vaccines. While tetravalent live-attenuated tetravalent vaccines (LATVs), which mimic natural infection by inducing both cellular and humoral immune responses, are still currently favored, developing a vaccine that provides a balanced immunity to all four DENV serotypes remains a challenge. With the recently advanced understanding of virion structure and B cell immune responses from naturally infected DENV patients, two points of view in developing a next-generation dengue vaccine emerged: one is to induce potent, type-specific neutralizing antibodies (NtAbs) recognizing quaternary structure-dependent epitopes by having four components of vaccine strains replicate equivalently; the other is to induce protective and broadly NtAbs against the four serotypes of DENV with a universal vaccine. This article reviews the studies related to these issues and the current knowledge gap that needs to be filled in.
- Therapeutic Vaccination Refocuses T-cell Responses Towards Conserved Regions of HIV-1 in Early Treated Individuals (BCN 01 study). [Journal Article]
- EEClinicalMedicine 2019 May-Jun; 11:65-80
- Strong and broad antiviral T-cell responses targeting vulnerable sites of HIV-1 will likely be a critical component for any effective cure strategy.
Strong and broad antiviral T-cell responses targeting vulnerable sites of HIV-1 will likely be a critical component for any effective cure strategy.
- Letter to the editor UC-II® Undenatured type II collagen: update to analytical methods. [Letter]
- JIJ Int Soc Sports Nutr 2019 Jul 16; 16(1):29
- Supplementation with UC-II® undenatured type II collagen has been shown to provide joint health benefits for both healthy adults and adults with knee osteoarthritis in controlled clinical trials. The…
Supplementation with UC-II® undenatured type II collagen has been shown to provide joint health benefits for both healthy adults and adults with knee osteoarthritis in controlled clinical trials. These trials used UC-II® materials with undenatured type II collagen characterized by an ELISA method that utilizes a monoclonal antibody specific for epitopes expressed by undenatured type II collagen protein only. In 2014, we modified the sample preparation part of the ELISA method in order to reduce the amount of time devoted to this procedure. We undertook these modifications in order to provide commercial manufacturers with a streamlined assay methodology better aligned with their product testing requirements. In doing so, it altered the percent of undenatured collagen now reported for UC-II® undenatured type II collagen. The intent of this letter is to clarify that the UC-II® materials used in the published clinical research cited herein, and the commercially available ingredient, remain identical and to describe the rationale for the change in the extraction method.
- An in silico approach towards identification of virulence factors in red complex pathogens targeted by reserpine. [Journal Article]
- NPNat Prod Res 2019 Jul 17; :1-6
- Oral cavity hosts an exhaustive collection of microorganisms which are known to be associated with disease such as dental caries, periodontal and deep-seated infections. Elimination of these pathogen…
Oral cavity hosts an exhaustive collection of microorganisms which are known to be associated with disease such as dental caries, periodontal and deep-seated infections. Elimination of these pathogens from the site of infection remains a perplexing task, which demands the use of antibiotics. The emergence of drug resistant forms has spurred interest into identifying novel therapeutic targets against these pathogens. In this context, the present study has been designed to analyse and identify potential drug targets of the phytocompound reserpine in red complex pathogens. Computational tools were used to identify the targets, assess its functional role and virulence property. Further, the peptide epitopes present in the virulence factors were identified using BepiPred tool. The subcellular location of the virulence proteins were also elucidated using PSORTb. Reserpine was found to target vital protein transporters such as ABC transporter and efflux pumps which are known to play a crucial role in the survival of bacterial cells. Hence the present in silico study provides substantial evidence on the anti-bacterial activity of reserpine against red complex pathogens. However, in vitro studies using the compound is warranted to further confirm the efficacy of the compound.
- Structural Differences Influence Biological Properties of Glucosylceramides from Clinical and Environmental Isolates of Scedosporium aurantiacum and Pseudallescheria minutispora. [Journal Article]
- JFJ Fungi (Basel) 2019 Jul 15; 5(3)
- Scedosporium/Lomentospora complex is composed of filamentous fungi, including some clinically relevant species, such as Pseudallescheria boydii, Scedosporium aurantiacum, and Scedosporium apiospermum…
Scedosporium/Lomentospora complex is composed of filamentous fungi, including some clinically relevant species, such as Pseudallescheria boydii, Scedosporium aurantiacum, and Scedosporium apiospermum. Glucosylceramide (GlcCer), a conserved neutral glycosphingolipid, has been described as an important cell surface molecule playing a role in fungal morphological transition and pathogenesis. The present work aimed at the evaluation of GlcCer structures in S. aurantiacum and Pseudallescheria minutispora, a clinical and an environmental isolate, respectively, in order to determine their participation in fungal growth and host-pathogen interactions. Structural analysis by positive ion-mode ESI-MS (electrospray ionization mass spectrometer) revealed the presence of different ceramide moieties in GlcCer in these species. Monoclonal antibodies against Aspergillus fumigatus GlcCer could recognize S. aurantiacum and P. minutispora conidia, suggesting a conserved epitope in fungal GlcCer. In addition, these antibodies reduced fungal viability, enhanced conidia phagocytosis by macrophages, and decreased fungal survival inside phagocytic cells. Purified GlcCer from both species led to macrophage activation, increasing cell viability as well as nitric oxide and superoxide production in different proportions between the two species. These results evidenced some important properties of GlcCer from species of the Scedosporium/Lomentospora complex, as well as the effects of monoclonal anti-GlcCer antibodies on fungal cells and host-pathogen interaction. The differences between the two species regarding the observed biological properties suggest that variation in GlcCer structures and strain origin could interfere in the role of GlcCer in host-pathogen interaction.
- Immunolocalization of β-(1-4)-D-galactan, xyloglucans and xylans in the reaction xylem fibres of Leucaena leucocephala (Lam.) de Wit. [Journal Article]
- PPPlant Physiol Biochem 2019 Jul 09; 142:217-223
- Cell wall architecture of tension wood fibres represents a suitable biological system to study the mechanism of growth and maintenance of posture of trees growing under various physical and physiolog…
Cell wall architecture of tension wood fibres represents a suitable biological system to study the mechanism of growth and maintenance of posture of trees growing under various physical and physiological growth constraints. In the present study, we investigated the spatial distributions of β-(1-4)-D-galactan, xyloglucan and xylans (both less and highly substituted) in the opposite and tension wood fibres of bent Leucaena leucocephala by immunolabelling with monoclonal antibodies LM5, CCRCM1, LM10 and LM11 specific to these carbohydrate epitopes. The presence of non-lignified, tertiary wall layer is the typical tension wood characteristic associated with the reaction xylem fibres in Leucaena. LM5 labelling of opposite fibres showed weak labelling in the cell walls indicating less concentration of β-(1-4)-D-galactans while tension wood showed strong labelling in the tertiary wall layer suggesting the gelatinous layer (G-layer) has a strong cross linking with β-(1-4)-D-galactans. Xyloglucan distribution was more in the compound middle lamellae and the primary wall-S1 layer boundary of tension wood fibres as compared to that of opposite wood. A weak labelling was also evident near the boundary between the G-layer and the secondary wall of tension wood fibres. The secondary wall of opposite and tension wood fibres showed a strong distribution of both ls ACG Xs (LM10) and hs ACG Xs (LM11) while a weak labelling was noticed in the compound middle lamella. Tension wood fibres also showed strong xylan labelling mainly confined to the lignified secondary walls while the G-layer showed weak xylan labelling. In conclusion, our results suggest that β-(1-4)-D-galactans and xyloglucans could be implicated in the tensile stress generation within the G-layer of tension wood fibres of Leucaena leucocephala.
- Assessment of Proteus mirabilis Antigen Immunological Complexes by Atomic Force Microscopy. [Journal Article]
- MMMethods Mol Biol 2019; 2021:273-283
- Atomic force microscopy (AFM) is being increasingly used to directly measure protein interactions in nearly physiological environments. Here, protocols for atomic force microscopy (AFM) for visualiza…
Atomic force microscopy (AFM) is being increasingly used to directly measure protein interactions in nearly physiological environments. Here, protocols for atomic force microscopy (AFM) for visualization of antigen-antibody complexes are presented. The technique is used to demonstrate complexes formed by rheumatoid arthritis patient antibodies with lipopolysaccharide (LPS) isolated from P. mirabilis (O3) strain S1959 and a synthetic antigen (LPS epitope of 6 N-alpha-(D-galacturonoyl)-L-lysine residues).
- Nucleotide Substitutions in Hepatitis B Viruses Derived from Chronic HBV Patients. [Journal Article]
- MJMediterr J Hematol Infect Dis 2019; 11(1):e2019046
- CONCLUSIONS: Our results showed common mutations within HBsAg, occurring in immune epitopes, a high rate of G1896A mutations in the PC region, and a negative correlation between the emergence of A1762T/G1764A mutation and the G1764T/C1766G mutant in the BCP region.
- Immunological evidence for in vivo production of novel advanced glycation end-products from 1,5-anhydro-D-fructose, a glycogen metabolite. [Journal Article]
- SRSci Rep 2019 Jul 15; 9(1):10194
- The anhydrofructose pathway is an alternate pathway for glycogen degradation by α-1,4-glucan lyase. The sugar 1,5-anhydro-D-fructose (1,5-AF) acts as the central intermediate of this pathway, but its…
The anhydrofructose pathway is an alternate pathway for glycogen degradation by α-1,4-glucan lyase. The sugar 1,5-anhydro-D-fructose (1,5-AF) acts as the central intermediate of this pathway, but its physiological role of in mammals is unclear. Glycation reactions forming advanced glycation end-products (AGEs) are important in the development of complications of diabetes mellitus. We hypothesized that 1,5-AF may contribute to cellular damage by forming 1,5-AF-derived AGEs (AF-AGEs) with intracellular proteins. To clarify the role of 1,5-AF in protein modification, we created a novel antibody targeting AF-AGEs. Serum albumin modified by AF-AGEs was prepared by incubating rabbit serum albumin (RSA) or bovine serum albumin (BSA) with 1,5-AF. After immunizing rabbits with AF-AGEs-RSA, affinity chromatography of anti-AF-AGE antiserum was performed on a Sepharose 4B column coupled with AF-AGEs-BSA or N-(carboxymethyl)/N-(carboxyethyl)lysine-BSA. A novel immunopurified anti-AF-AGE antibody was obtained and was characterized using a competitive enzyme-linked immunosorbent assay. Then an AF-AGEs assay was established using this immunopurified antibody. This assay was able to detect AF-AGEs in human and animal serum samples. Finally, intracellular accumulation of AF-AGEs was shown to be associated with damage to cultured hepatocytes (HepG2 cells). This is the first report about in vivo detection of AF-AGEs with a novel structural epitope.
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- A Cross-reactive Protein Vaccine Combined with PCV-13 Prevents Streptococcus pneumoniae- and Haemophilus influenzae-mediated Acute Otitis Media. [Journal Article]
- IIInfect Immun 2019 Jul 15
- Acute otitis media is one of the most common childhood infections worldwide. Currently licensed vaccines against the common otopathogen, Streptococcus pneumoniae, target the bacterial capsular polysa…
Acute otitis media is one of the most common childhood infections worldwide. Currently licensed vaccines against the common otopathogen, Streptococcus pneumoniae, target the bacterial capsular polysaccharide and confer no protection against non-encapsulated strains or capsular types outside of vaccine coverage. Mucosal infections such as acute otitis media remain prevalent, even those caused by vaccine-covered serotypes. Here we report that a protein-based vaccine, a fusion construct of epitopes of CbpA to pneumolysin toxoid, confers effective protection against pneumococcal acute otitis media for non-PCV-13 serotypes and enhances protection for PCV-13 serotypes when co-administered with PCV-13. Having crossreactive epitopes, the fusion protein also induces potent antibody responses against non-typeable Haemophilus influenzae and S. pneumoniae, engendering protection against acute otitis media caused by emerging unencapsulated otopathogens. These data suggest that augmenting capsule-based vaccination with conserved, cross-reactive protein-based vaccines may broaden and enhance protection against acute otitis media.