Amino acid starvation enhances vaccine efficacy by augmenting neutralizing antibody production.

Amino acid starvation enhances vaccine efficacy by augmenting neutralizing antibody production. Sci Signal. 2019 Nov 12;12(607): Authors: Afroz S, Shama, Battu S, Matin S, Solouki S, Elmore JP, Minhas G, Huang W, August A, Khan N Abstract Specific reduction in the intake of proteins or amino acids (AAs) offers enormous health benefits, including increased life span, protection against age-associated disorders, and improved metabolic fitness and immunity. Cells respond to conditions of AA starvation by activating the amino acid starvation response (AAR). Here, we showed that mimicking AAR with halofuginone (HF) enhanced the magnitude and affinity of neutralizing, antigen-specific antibody responses in mice immunized with dengue virus envelope domain III protein (DENVrEDIII), a potent vaccine candidate against DENV. HF enhanced the formation of germinal centers (GCs) and increased the production of the cytokine IL-10 in the secondary lymphoid organs of vaccinated mice. Furthermore, HF promoted the transcription of genes associated with memory B cell formation and maintenance and maturation of GCs in the draining lymph nodes of vaccinated mice. The increased abundance of IL-10 in HF-preconditioned mice correlated with enhanced GC responses and may promote the establishment of long-lived plasma cells that secrete antigen-specific, high-affinity antibodies. Thus, these data suggest that mimetics of AA starvation could provide an alternative strategy to augmen...
Source: Science Signaling - Category: Biomedical Science Authors: Tags: Sci Signal Source Type: research

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Canadian Journal of Microbiology, e-First Articles. Zika virus (ZIKV) is a mosquito-borne virus that was first isolated from Zika forest, Uganda, in 1947. Since its inception, major and minor outbreaks have been documented from several parts of world. Aedes spp. mosquitoes are the primary vectors of ZIKV, but the virus can also be transmitted through sexual practices, materno-fetal transmission, and blood transfusion. The clinical presentations of symptomatic ZIKV infections are similar to dengue and chikungunya, including fever, headache, arthralgia, retro-orbital pain, conjunctivitis, and rash. ZIKV often causes mild ill...
Source: Canadian Journal of Microbiology - Category: Microbiology Authors: Source Type: research
Eliciting broadly neutralizing antibodies (bNAbs) against the four dengue virus serotypes (DENV1-4) that are spreading into new territories is an important goal of vaccine design. To define bNAb targets, we characterized 28 antibodies belonging to expanded and hypermutated clonal families identified by transcriptomic analysis of single plasmablasts from DENV-infected individuals. Among these, we identified J9 and J8, two somatically related bNAbs that potently neutralized DENV1-4. Mutagenesis studies showed that the major recognition determinants of these bNAbs are in E protein domain I, distinct from the only known class ...
Source: eLife - Category: Biomedical Science Tags: Immunology and Inflammation Microbiology and Infectious Disease Source Type: research
Abstract Dengue is one of the most serious mosquito-borne viral diseases occurring in humans. From their complexity of 4 serotypes, the ideal vaccine for dengue should be able to stimulate cross-neutralizing antibodies. Recently, genetic-based immune response have been studied for guiding of vaccine design for several viral pathogens. Despite a recent approval of dengue vaccine, the information of genetics-based immune response against dengue virus (DENV) are still limited. Consequently, we aimed to determine the profiles of immunoglobulin heavy chain gene from DENV2 infected patients. The immunoglobulin heavy cha...
Source: Japanese Journal of Infectious Diseases - Category: Infectious Diseases Authors: Tags: Jpn J Infect Dis Source Type: research
Source: ScienceNOW - Category: Science Authors: Tags: letters Source Type: news
(Cornell University) In a new paper in Science Signaling, researchers at the University of Hyderabad in India and the Cornell University College of Veterinary Medicine show that a plant-based compound called halofuginone improves the immune response to a potential vaccine against dengue virus.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
Conclusion: The study highlights the importance of behavioral change for knowledge and attitude to have significant effect to practices against DF. Thus, we recommend two comprehensive health programs, Communication for Behavioral Impact (COMBI) and Health Belief Model (HBM).
Source: International Journal of Environmental Research and Public Health - Category: Environmental Health Authors: Tags: Article Source Type: research
An additional six months of data from a late-stage trial of Takeda Pharmaceutical Co's experimental dengue vaccine again showed it failed to protect against one of the four types of the virus in an important patient group, researchers said on Saturday.
Source: Reuters: Health - Category: Consumer Health News Tags: healthNews Source Type: news
Publication date: Available online 21 November 2019Source: The Brazilian Journal of Infectious DiseasesAuthor(s): Gilma Sánchez-Burgos, Carla Herrera-Nájera, Roberto Cedillo-Rivera, Eric DumonteilAbstractThe antigenic potential of seven immunogenic peptides of the dengue virus was evaluated in the sera of patients with dengue confirmed by IgM/IgG serology. Antibodies IgM and IgG against dengue virus peptides were analyzed by ELISA in 31 dengue sero-positive and 20 sero-negative patients. The P5 peptide showed significant IgG immunoreactivity mostly in the sera of patients with dengue without warning signs in ...
Source: The Brazilian Journal of Infectious Diseases - Category: Infectious Diseases Source Type: research
Dumonteil E Abstract The antigenic potential of seven immunogenic peptides of the dengue virus was evaluated in the sera of patients with dengue confirmed by IgM/IgG serology. Antibodies IgM and IgG against dengue virus peptides were analyzed by ELISA in 31 dengue sero-positive and 20 sero-negative patients. The P5 peptide showed significant IgG immunoreactivity mostly in the sera of patients with dengue without warning signs in comparison with patients with dengue with warning signs, correlating with mild disease. This finding suggests that the low antibody response against P5 epitope could be a risk factor for h...
Source: Braz J Infect Dis - Category: Infectious Diseases Authors: Tags: Braz J Infect Dis Source Type: research
Understanding T  cell responses to dengue infection is important for developing effective vaccines. Chng et al. used high-dimensional CyTOF profiling and peptide-HLA tetramer screening to track dengue-specific T cell activation and differentiation into memory cells in naturally infected patients. They found that dengue infection causes broad immune cell activation and that dengue-specific T cells differentiate into two major cell fates.
Source: Immunity - Category: Allergy & Immunology Authors: Tags: Resource Source Type: research
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