- Influenza Virus Research Studies
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- interferon and immune responses
- Respiratory viral infections research
- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
- Viral gastroenteritis research and epidemiology
- Monoclonal and Polyclonal Antibodies Research
- Viral-associated cancers and disorders
- Virus-based gene therapy research
- SARS-CoV-2 and COVID-19 Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Diabetes and associated disorders
- Pancreatic function and diabetes
- Xenotransplantation and immune response
- Reproductive System and Pregnancy
- Animal Virus Infections Studies
- Cytokine Signaling Pathways and Interactions
- Complement system in diseases
- Animal Disease Management and Epidemiology
- vaccines and immunoinformatics approaches
- Viral Infections and Vectors
Centers for Disease Control and Prevention
2015-2024
National Center for Immunization and Respiratory Diseases
2014-2024
Center for Disease Control
2019
Emory University
2003-2013
Centers for Disease Control and Prevention
2011
Emory Healthcare
2006-2008
Weatherford College
2008
National Influenza Center
2006
Washington University in St. Louis
2002-2004
National Center for Infectious Diseases
2004
ABSTRACT Highly pathogenic avian H5N1 influenza viruses are now widespread in poultry Asia and have recently spread to some African European countries. Interspecies transmission of these humans poses a major threat public health. To better understand the basis pathogenesis viruses, we investigated role proinflammatory cytokines transgenic mice deficient interleukin-6 (IL-6), macrophage inflammatory protein 1 alpha (MIP-1α), IL-1 receptor (IL-1R), or tumor necrosis factor (TNFR1) by use two A...
The molecular composition and binding epitopes of the immunoglobulin G (IgG) antibodies that circulate in blood plasma after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are unknown. Proteomic deconvolution IgG repertoire to spike glycoprotein convalescent subjects revealed response is directed predominantly (>80%) against residing outside receptor domain (RBD). In one subject, just four lineages accounted for 93.5% response, including an amino (N)-terminal...
Corneal infection with herpes simplex virus-1 in immunocompetent mice induces an immunopathologic response termed herpetic stromal keratitis (HSK). The earliest sign of disease is neutrophil infiltration, which lasts for 48 to 72 h and then disappears. However, a secondary this time more massive, occurs, beginning 8 9 days postinfection, HSK becomes clinically evident. role neutrophils expression was investigated by eliminating such cells using specific mAb (RB6-8C5). In neutrophil-depleted...
Many chronic viral infections are marked by pathogen persistence and a generalized immunosuppression. The exact mechanisms which this occurs still unknown. Using mouse model of persistent lymphocytic choriomeningitis virus (LCMV) infection, we demonstrate targeting fibroblastic reticular cells (FRC) in the lymphoid organs. FRC stromal networks critical for proper architecture function. High numbers were infected LCMV clone 13, causes whereas few acute strain, Armstrong. function conduit...
Abstract Tunneling nanotubes (TNTs) represent a novel route of intercellular communication. While previous work has shown that TNTs facilitate the exchange viral or prion proteins from infected to naïve cells, it is not clear whether genome also transferred via this mechanism and further, transfer can result in productive replication infectious agents recipient cell. Here we present evidence lung epithelial cells are connected by TNTs, spite presence neutralizing antibodies an antiviral...
Protein energy malnutrition (PEM), a common cause of secondary immune deficiency in children, is associated with an increased risk infections. Very few studies have addressed the relevance PEM as factor for influenza.
Abstract Background Enhanced influenza vaccines may improve protection for older adults, but comparative immunogenicity data are limited. Our objective was to examine immune responses enhanced vaccines, compared standard-dose in community-dwelling adults. Methods Community-dwelling adults aged 65–82 years Hong Kong were randomly allocated (October 2017–January 2018) receive 2017–2018 Northern hemisphere formulations of a quadrivalent vaccine, MF59-adjuvanted trivalent high-dose or...
After a brief period of antigenic stimulation, T cells become committed to program autonomous expansion and differentiation. We investigated the role antigen-specific cell precursor frequency as possible cell-extrinsic factor impacting programming in model allogeneic tissue transplantation. Using an adoptive transfer system incrementally raise CD8(+) cells, we found that donor-reactive primed at low exhibited increased cellular division, decreased development multifunctional effector...
Sirolimus is a potent antiproliferative agent used clinically to prevent renal allograft rejection. However, little known about the effects of maintenance immunosuppressive agents on immune response potentially protective vaccines. Here we show that sirolimus paradoxically increases magnitude and quality CD8+ T-cell vaccinia vaccination in nonhuman primates, fostering more robust recall responses compared untreated tacrolimus-treated controls. Enhancement both central effector memory...
Widespread distribution of highly pathogenic avian H5N1 influenza viruses in domesticated and wild birds continues to pose a threat public health, as interspecies transmission virus has resulted increasing numbers human disease cases. Although the mechanism(s) not been fully elucidated, it suggested that ability evade host innate responses, such type I interferon response, may contribute virulence these mammals. We investigated role interferons (alpha/beta [IFN-alpha/beta]) might play...
ABSTRACT Pattern recognition receptors (PRR) sense certain molecular patterns uniquely expressed by pathogens. Retinoic-acid-inducible gene I (RIG-I) is a cytosolic PRR that senses viral nucleic acids and induces innate immune activation secretion of type interferons (IFNs). Here, using influenza vaccine antigens, we investigated the consequences activating RIG-I pathway for antigen-specific adaptive responses. We found mice immunized with antigens coadministered 5′ppp-double-stranded RNA...
SUMMARY Although humoral immunity is essential for control of SARS-CoV-2, the molecular composition, binding epitopes and effector functions immunoglobulin G (IgG) antibodies that circulate in blood plasma following infection are unknown. Proteomic deconvolution circulating IgG repertoire (Ig-Seq 1 ) to spike ectodomain (S-ECD 2 four convalescent study subjects revealed response oligoclonal directed predominantly (>80%) S-ECD lie outside receptor domain (RBD). When comparing either RBD,...
Abstract Repeat vaccination with egg-based influenza vaccines could preferentially boost antibodies targeting the egg-adapted epitopes and reduce immunogenicity to circulating viruses. In this randomized trial (Clinicaltrials.gov: NCT03722589), sera pre- post-vaccination quadrivalent inactivated (IIV4), cell culture-based (ccIIV4), recombinant (RIV4) were collected from healthcare personnel (18-64 years) in 2018−19 ( N = 723) 2019−20 684) seasons. We performed an exploratory analysis....
Many γ-herpesviruses encode candidate oncogenes including homologues of host bcl-2 and cyclin proteins (v-bcl-2, v-cyclin), but the physiologic roles these genes during infection are not known. We show for first time in any virus system role v-bcl-2. A γ-herpesvirus v-bcl-2 was essential efficient ex vivo reactivation from latent infection, both persistent replication virulence chronic immunocompromised (interferon [IFN]-γ−/−) mice. The v-cyclin also critical same stages pathogenesis....
In this report we investigated whether induction of IL-12 occurs in response to herpes simplex virus (HSV) infection the mouse eye, which may serve regulate nature subsequent immune response. The data show early and continued maintenance (p40) mRNA cornea draining lymph node upon ocular with HSV. Using a very sensitive radioimmunoassay technique, protein also was detected HSV infection. Unfractionated splenocytes enriched populations dendritic cells, macrophages, neutrophils all responded...
Abstract Blockade of the CD40/CD154 signaling pathway using anti-CD154 Abs has shown promise in attenuating alloimmune response and promoting long-term graft survival murine model systems, although side effects observed humans have hampered its progression through clinical trials. Appropriately designed anti-CD40 may provide a suitable alternative. We investigated two isoforms novel monoclonal rat anti-mouse CD40 Ab (7E1) for characteristics mirroring those anti-CD154: 7E1-G1 (an IgG1...
Abstract Myeloid dendritic cells (mDCs) have long been thought to function as classical APCs for T cell responses. However, we demonstrate that influenza viruses induce rapid differentiation of human monocytes into mDCs. Unlike the classic mDCs, virus-induced mDCs failed upregulate DC maturation markers and were unable allogeneic lymphoproliferation. Virus-induced secreted little, if any, proinflammatory cytokines; however, they a substantial amount chemoattractants (MCP-1 IP-10)....
The NLR protein, NLRC5 is an important regulator of MHC class I gene expression, however, the role in other innate immune responses less well defined. In present study, we report that binds RIG-I and this interaction critical for robust antiviral against influenza virus. Overexpression human lung epithelial cell line, A549, normal bronchial cells resulted impaired replication virus A/Puerto Rico/8/34 (PR8) enhanced IFN-β expression. Influenza leads to induction drives expression host cells....
The vaccine efficacy of standard-dose seasonal inactivated influenza vaccines (S-IIV) can be improved by the use with higher antigen content or adjuvants. We conducted a randomized controlled trial in older adults to compare cellular and antibody responses S-IIV versus enhanced (eIIV): MF59-adjuvanted (A-eIIV), high-dose (H-eIIV), recombinant-hemagglutinin (HA) (R-eIIV). All induced comparable H3-HA-specific IgG elevated antibody-dependent cytotoxicity (ADCC) activity at day 30 post...
Abstract Herpes simplex virus infection of mouse corneas can lead to the development an immunopathological lesion, termed herpetic stromal keratitis (HSK). Such lesions also occur in TCR-transgenic mice backcrossed SCID (TgSCID) that are unable mount detectable HSV-specific immune responses. The present study demonstrates lesion expression such depends on continuous viral replication, whereas immunocompetent mice, occurred even if replication was terminated at 4 days after infection. TgSCID...
Herpetic stromal keratitis (HSK) is a CD4+ T cell-controlled immunopathologic lesion in the eye that results from infection with herpes simplex virus (HSV). Target Ags involved HSK remain undefined. In this study, we determined if could be induced animals genetically incapable of generating HSV Ag-specific cells. Mice bearing transgenic TCR specific to OVA peptide 323-339 (DO11.10) were crossed SCID mice whose offspring (Tg-SCID) possessed cells, >98% which expressed peptide-specific TCR....