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Site: http://phys.org/biology-news/

Funded by grants from the National Institutes of Health, scientists at Blood Systems Research Institute (BSRI) in San Francisco and the Washington University School of Medicine in St. Louis have found that neutralizing antibodies that engage epitopes including residue E2-W64 are highly potent at inhibiting the virus in mice, due to the importance of E2-W64 in pathogenicity. Furthermore, these antibodies prevent CHIKV from both entering and exiting cells, whereas prior studies of neutralizing antibodies to CHIKV and multiple other classes of viruses have focused on the capacity to block viruses from entering a cell. The research was published today in Cell Reports. Dr. Graham Simmons, associate investigator at BSRI and the lead researcher on the project, together with Dr. Jing Jin, a postdoctoral fellow in his laboratory, view these recent discoveries in the scope of a greater body of work that he and other researchers are doing to understand and combat CHIKV and other viruses. "Inhibiting chikungunya virus, both at the points of entry and release from cells, is another important piece in the puzzle that could lead to new approaches in therapeutics and vaccines to fight infectious diseases," explains Simmons. Last month, a team led by Dr. Michael Diamond of the Washington University School of Medicine in St. Louis and that included Drs. Simmons and Jin, published related research in the journal Cell. Diamond's team found that a panel of cross-neutralizing monoclonal antibodies can potently inhibit both entry and release of more than one alphavirus. This result, effectively a method for blocking the spread of alphaviruses between cells, is one that could eventually lead to a single vaccine that protects against multiple viruses. Such a vaccine would represent a major milestone in global infectious disease prevention. "But for chikungunya specifically," continues Simmons, "more research is still needed to know whether the virus can be transmitted via blood transfusion and if the recipient of the infected blood develops symptoms." In the past decade, CHIKV, a mosquito-borne virus, has spread from endemic areas of Africa and Asia to Europe and the Americas, infecting millions. Infection causes high fever, often accompanied by severe joint pain, which can lead to chronic arthritis. It is not yet known if CHIKV is transmitted through blood transfusion from an infected donor; no cases of transfusion-transmitted CHIKV have been reported to date. Currently, there is no FDA-approved vaccine or blood screening test for CHIKV, and research continues. "Our mission is to ensure the safety of the world's blood supplies and to prevent the transmission of viruses like chikungunya through blood transfusions," explains Dr. Michael Busch, senior vice president and director of BSRI. To better understand chikungunya infection rates in the blood supply, BSRI, in collaboration with the U.S. Centers for Disease Control, Puerto Rico Blood Banks, Creative Testing Solutions and Hologic, a company that manufactures blood screening assays, recently completed a large study that documented very high rates of infected donations during the 2014 outbreak in Puerto Rico which infected nearly 25% of the territory's population. Data from that study were presented at the 2015 meeting of the American Society of Tropical Medicine and Hygiene (ASTMH) in October and are expected to be submitted in the next month for publication. BSRI, together with colleagues in the Recipient Epidemiology and Donor Evaluation Study-III Brazil team and Hologic, also recently received supplemental funding from the National Heart, Lung and Blood Institute of the National Institutes of Health to conduct a study in São Paolo, Brazil, to establish whether transfusion transmission of chikungunya occurs, and if so, the clinical consequences of infection in transfusion recipients. The study will begin in 2016 or 2017, in response to further CHIKV outbreaks in Brazil.

Plourde A.R.,University of California at San Francisco | Bloch E.M.,Johns Hopkins University | Bloch E.M.,Blood Systems Research Institute
Emerging Infectious Diseases | Year: 2016

Zika virus is a mosquitoborne flavivirus that is the focus of an ongoing pandemic and public health emergency. Previously limited to sporadic cases in Africa and Asia, the emergence of Zika virus in Brazil in 2015 heralded rapid spread throughout the Americas. Although most Zika virus infections are characterized by subclinical or mild influenza-like illness, severe manifestations have been described, including Guillain-Barre syndrome in adults and microcephaly in babies born to infected mothers. Neither an effective treatment nor a vaccine is available for Zika virus; therefore, the public health response primarily focuses on preventing infection, particularly in pregnant women. Despite growing knowledge about this virus, questions remain regarding the virus’s vectors and reservoirs, pathogenesis, genetic diversity, and potential synergistic effects of co-infection with other circulating viruses. These questions highlight the need for research to optimize surveillance, patient management, and public health intervention in the current Zika virus epidemic. © 2016, Centers for Disease Control and Prevention (CDC). All rights reserved. Source

Jackman R.P.,Blood Systems Research Institute
Blood | Year: 2013

In the Trial to Reduce Alloimmunization to Platelets (TRAP) study, 101 of 530 participants became refractory to platelet transfusions without evidence of HLA or human platelet antigen (HPA) antibodies. We used a more sensitive bead-based assay to detect and quantify HLA antibodies and a qualitative solid-phase enzyme-linked immunosorbet assay for HPA to determine whether low-level antibodies could predict refractoriness in longitudinal panels from 170 lymphocytotoxicity assay (LCA)(-) and 20 LCA(+) TRAP participants. All TRAP recipients who previously tested LCA(+) were HLA antibody(+), using the bead-based system. Levels of HLA or HPA antibodies did not predict refractoriness among LCA(-) recipients, although higher levels of HLA antibodies were associated with refractoriness among LCA(+) recipients. These data demonstrate that weak to moderate HLA antibody levels detectable by modern binding assays are not associated with platelet refractoriness. Source

BACKGROUND: HLA antibodies might contribute to the pathogenesis of transfusion-related acute lung injury (TRALI). HLA antibody detection methods include ELISA, flow cytometry, and multiplex bead-based assays, as well as the older lymphocytotoxicity assay, and it is not obvious how to compare results across platforms. STUDY DESIGN AND METHODS: Five hundred twenty-five serum samples were selected from 7841 donors in the Leukocyte Antibody Prevalence Study (LAPS) repository based on risk for the development of HLA antibodies, using the number of pregnancies as the risk factor. Subjects included 81 males and females with 0 (n = 187), 1 (n = 67), or 2+ pregnancies (n = 190). Replicate frozen serum aliquots were sent blinded to four different HLA antibody assay manufacturers for detection using five different assays. RESULTS: The flow cytometry and multiplex bead based-assays typically resulted in a larger proportion of HLA antibody positive samples compared with ELISA based assays. Latent variable analysis was used to derive a new set of consensus cutoffs, which yielded similar sensitivities across test platforms and increased concordance amongst assays. Assay agreement was higher in ever pregnant females than in males and never-pregnant females. CONCLUSIONS: Different assays resulted in varied positivity rates when the manufacturer's suggested cutoffs were used, demonstrating that care needs to be taken when comparing clinical outcomes data generated using different HLA antibody assays and testing platforms. The method used here, involving latent variable analysis, presents one possible approach to calculating comparable cutoffs that result in broad agreement across assays with respect to positivity designation. © 2010 American Association of Blood Banks. Source

Jackman R.P.,Blood Systems Research Institute
Current Opinion in Anaesthesiology | Year: 2013

Purpose of Review: Traumatic injury is a major human health problem, with many injured people supported by transfusion of allogeneic blood. Although trauma and transfusion have both been known to have immunomodulatory effects for some time, little is known about their combined effects or the scope and kinetics of such responses. Recent Findings: Traumatic injury has a profound immunomodulatory effect on the patient, affecting a broad array of immunological components. This can be further complicated by transfusion, though the contribution of transfusion relative to the massive response triggered by trauma is small. The response to trauma involves a strong immunosuppressive component, which, contrary to the systemic inflammatory response syndrome/compensatory anti-inflammatory response syndrome model, occurs at the earliest time points examined and overlaps with proinflammatory and antimicrobial elements. This response is remarkably similar in a wide range of patients with different types and severities of injury. Summary: The response to trauma and transfusion involves a massive and rapid reorganization of the immune system that can put the patient at increased risk of infection, tissue damage, and organ failure. The scope of the response presents challenges to the development of treatments to control this dysregulation. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

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