A High-Dimensional Atlas of Human T Cell Diversity Reveals Tissue-Specific Trafficking and Cytokine Signatures.
Immunity 45(2):442 (2016)
Depending on the tissue microenvironment, T cells can differentiate into highly diverse subsets expressing unique trafficking receptors and cytokines. Studies of human lymphocytes have primarily focused on a limited number of parameters in blood, representing an incomplete view of the human immu...
Low antibody titers 5 years after vaccination with the CYD-TDV dengue vaccine in both pre-immune and naïve vaccinees.
Human Vaccines & Immunotherapeutics 12(5):1265 (2016)
Globally, dengue virus (DENV) is one of the most widespread vector-borne viruses. Dengue disease affects populations in endemic areas and, increasingly, tourists who travel to these countries, but there is currently no approved vaccine for dengue. A phase 3 efficacy trial with Sanofi-Pasteur's r...
Tetravalent dengue DIIIC protein together with alum and ODN elicits a Th1 response and neutralizing antibodies in mice.
Vaccine 33(12):1474 (2015)
Dengue disease is a global challenge for healthcare systems particularly during outbreaks, and millions of dollars are spent every year for vector control. An efficient and safe vaccine that is cost-effective could resolve the burden that dengue virus imposes on affected countries. We describe h...
Selective susceptibility of human skin antigen presenting cells to productive dengue virus infection.
PLoS Pathogens 10(12):e1004548 (2014)
Dengue is a growing global concern with 390 million people infected each year. Dengue virus (DENV) is transmitted by mosquitoes, thus host cells in the skin are the first point of contact with the virus. Human skin contains several populations of antigen-presenting cells which could drive the im...
Kinome siRNA screen identifies novel cell-type specific dengue host target genes.
Antiviral Research 110:20 (2014)
Dengue is a global emerging infectious disease, with no specific treatment available. To identify novel human host cell targets important for dengue virus infection and replication, an image-based high-throughput siRNA assay screening of a human kinome siRNA library was conducted using human hep...
Human regulatory B cells combine phenotypic and genetic hallmarks with a distinct differentiation fate.
Journal of Immunology 193(5):2258 (2014)
Regulatory B cells (B-reg) produce IL-10 and suppress inflammation in both mice and humans, but limited data on the phenotype and function of these cells have precluded detailed assessment of their contribution to host immunity. In this article, we report that human B-reg cannot be defined based...
Type I interferon signals in macrophages and dendritic cells control dengue virus infection: implications for a new mouse model to test dengue vaccines.
Journal of Virology 88(13):7276 (2014)
Dengue virus (DENV) infects an estimated 400 million people every year, causing prolonged morbidity and sometimes mortality. Development of an effective vaccine has been hampered by the lack of appropriate small animal models; mice are naturally not susceptible to DENV and only become infected i...
Flavivirus RNA methylation.
Journal of General Virology 95(Pt 4):763 (2014)
The 5' end of eukaryotic mRNA contains the type-1 (m7GpppNm) or type-2 (m7GpppNmNm) cap structure. Many viruses have evolved various mechanisms to develop their own capping enzymes (e.g. flavivirus and coronavirus) or to 'steal' caps from host mRNAs (e.g. influenza virus). Other viruses have dev...
A three-dimensional atlas of human dermal leukocytes, lymphatics, and blood vessels.
Journal of Investigative Dermatology 134(4):965 (2014)
Dendritic cells (DCs), macrophages (Mφ), and T cells are major components of the skin immune system, but their interstitial spatial organization is poorly characterized. Using four-channel whole-mount immunofluorescence staining of the human dermis, we demonstrated the three-dimensional distribu...
Live attenuated vaccine: the first clinically approved dengue vaccine?
Expert Review of Vaccines 13(2):185 (2014)
Dengue virus (DENV) is the most prevalent mosquito-borne viral pathogen in humans. There are 390 million human infections each year, with 96 million infections exhibiting disease symptoms. Currently, there is no clinically approved vaccine and antiviral for DENV. The four serotypes of DENV (DENV...
Activation of peripheral blood mononuclear cells by dengue virus infection depotentiates balapiravir.
Journal of Virology 88(3):1740 (2014)
In a recent clinical trial, balapiravir, a prodrug of a cytidine analog (R1479), failed to achieve efficacy (reducing viremia after treatment) in dengue patients, although the plasma trough concentration of R1479 remained above the 50% effective concentration (EC(50)). Here, we report experiment...
Dengue serotype cross-reactive, anti-e protein antibodies confound specific immune memory for 1 year after infection.
Frontiers in Immunology 5:388 (2014)
Dengue virus has four serotypes and is endemic globally in tropical countries. Neither a specific treatment nor an approved vaccine is available, and correlates of protection are not established. The standard neutralization assay cannot differentiate between serotype-specific and serotype cross-...
Rational design of a live attenuated dengue vaccine: 2'-o-methyltransferase mutants are highly attenuated and immunogenic in mice and macaques.
PLoS Pathogens 9(8):e1003521 (2013)
Dengue virus is transmitted by Aedes mosquitoes and infects at least 100 million people every year. Progressive urbanization in Asia and South-Central America and the geographic expansion of Aedes mosquito habitats have accelerated the global spread of dengue, resulting in a continuously increas...
Plasmablasts generated during repeated dengue infection are virus glycoprotein-specific and bind to multiple virus serotypes.
Journal of Immunology 189(12):5877 (2012)
Dengue virus immune protection is specific to the serotype encountered and is thought to persist throughout one's lifetime. Many serotype cross-reactive memory B cells isolated from humans with previous dengue infection are specific for the nonstructural and the prM structural viral proteins, an...
Electrochemical impedance spectroscopy characterization of nanoporous alumina dengue virus biosensor.
Bioelectrochemistry 88:15 (2012)
The Faradaic electrochemical impedance technique is employed to characterize the impedance change of a nanoporous alumina biosensor in response towards the specific binding of dengue serotype 2 (Denv2) viral particles to its serotype 2-specific immunoglobulin G antibody within the thin alumina l...
Human poly- and cross-reactive anti-viral antibodies and their impact on protection and pathology.
Immunologic Research 53(1-3):148 (2012)
Anti-viral immune responses have been studied extensively in order to inform rational vaccine design. Following viral infection, the balance of pathologic and protective antibody responses in the host can critically influence clinical outcomes. Comparisons of the different classes of antibodies ...
Susceptibility and response of human blood monocyte subsets to primary dengue virus infection.
PLoS ONE 7(5):e36435 (2012)
Human blood monocytes play a central role in dengue infections and form the majority of virus infected cells in the blood. Human blood monocytes are heterogeneous and divided into CD16(-) and CD16(+) subsets. Monocyte subsets play distinct roles during disease, but it is not currently known if m...
Origin and Function of Circulating Plasmablasts during Acute Viral Infections.
Frontiers in Immunology 3:78 (2012)
Activated B cells proliferate and differentiate into antibody-producing cells, long-lived plasma cells, and memory B cells after immunization or infection. Repeated encounter of the same antigen triggers the rapid re-activation of pre-existing specific memory B cells, which then potentially ente...
Dengue virus activates polyreactive, natural IgG B cells after primary and secondary infection.
PLoS ONE 6(12):e29430 (2011)
Dengue virus is transmitted by mosquitoes and has four serotypes. Cross-protection to other serotypes lasting for a few months is observed following infection with one serotype. There is evidence that low-affinity T and/or B cells from primary infections contribute to the severe syndromes often ...
Contribution of herpesvirus specific CD8 T cells to anti-viral T cell response in humans.
PLoS Pathogens 6(8):e1001051 (2010)
Herpesviruses infect most humans. Their infections can be associated with pathological conditions and significant changes in T cell repertoire but evidences of symbiotic effects of herpesvirus latency have never been demonstrated. We tested the hypothesis that HCMV and EBV-specific CD8 T cells c...