A5042974567- Viral-associated cancers and disorders
- Monoclonal and Polyclonal Antibodies Research
- HIV Research and Treatment
- Cytomegalovirus and herpesvirus research
- Immune Cell Function and Interaction
- SARS-CoV-2 and COVID-19 Research
- Viral gastroenteritis research and epidemiology
- Animal Virus Infections Studies
- Hepatitis C virus research
- Lymphoma Diagnosis and Treatment
- Chemokine receptors and signaling
- Influenza Virus Research Studies
- Hepatitis B Virus Studies
- T-cell and B-cell Immunology
- Glycosylation and Glycoproteins Research
- Mosquito-borne diseases and control
- Respiratory viral infections research
- Herpesvirus Infections and Treatments
- Immunotherapy and Immune Responses
- Systemic Lupus Erythematosus Research
- Toxin Mechanisms and Immunotoxins
- interferon and immune responses
- Clostridium difficile and Clostridium perfringens research
- Virology and Viral Diseases
- Protein purification and stability
Visterra (United States)
2015-2024
University of Massachusetts Chan Medical School
2004-2021
Carle Foundation Hospital
2021
Saint Louis University
2009
National Center for Immunization and Respiratory Diseases
2007
Centers for Disease Control and Prevention
2007
AlphaVax (United States)
2007
Triangle
2007
Harvard University
2001-2004
Dana-Farber Cancer Institute
2002-2004
Angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV, the novel coronavirus that causes severe acute respiratory syndrome [Li, W. Moore, M. J., Vasilieva, N., Sui, Wong, S. K., Berne, A., Somasundaran, M., Sullivan, J. L., Luzuriaga, Greenough, T. C., et al. (2003) Nature 426, 450–454]. We have identified different human cellular glycoprotein can serve as an alternative SARS-CoV. A lung cDNA library in vesicular stomatitis virus G pseudotyped retrovirus was transduced into...
When Epstein-Barr virus (EBV) infects B cells in vitro, the result is a proliferating lymphoblast that expresses at least nine latent proteins. It generally believed these are rigorously controlled vivo by cytotoxic T cells. Consistent with this, latently infected peripheral blood of healthy carriers not lymphoblasts. Rather, they resting memory probably subject to direct immunosurveillance lymphocytes (CTLs). patients become immunosuppressed, viral load increases blood. The expansion...
Epstein-Barr (EBV) is a powerful immortalizing virus for human B lymphocytes in vitro and associated with several neoplasias vivo. Previously, we have shown that the majority of EBV-infected cells peripheral blood healthy, persistently infected individuals do not express activated phenotype, e.g., high levels cell surface CD23 CD80 (B7), characteristically expressed on vitro-immortalized cells. Here, show > or = 90% CD23-, virus-infected are G0 therefore resting. The remaining may be G1...
Clostridium difficile is the leading cause of nosocomial antibiotic-associated diarrhea, and recent outbreaks strains with increased virulence underscore importance identifying novel approaches to treat prevent relapse difficile-associated diarrhea (CDAD). CDAD pathology induced by two exotoxins, toxin A B, which have been shown be cytotoxic and, in case A, enterotoxic. In this report we describe fully human monoclonal antibodies (HuMAbs) that neutralize these toxins disease hamsters....
A novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), has recently been identified as the causative agent of (SARS). SARS-CoV appears similar to other coronaviruses in both virion structure and genome organization. It is known for that spike (S) glycoprotein required viral attachment permissive cells fusion envelope with host cell membrane. Here we describe construction expression a soluble codon-optimized S comprising first 1,190 amino acids native (S(1190)). The...
CXCR4, a member of the G protein-coupled receptor family proteins, is for stromal cell-derived factor (SDF-1 alpha) and principal coreceptor human immunodeficiency virus type 1 (HIV-1). CXCR4 has also been implicated in breast cancer metastasis. We examined ability to homomultimerize detergent-solubilized cell lysates membranes intact cells. was found multimerize containing detergents CHAPSO or Cymal-7 but not other that have shown disrupt native conformation CXCR4. expression levels did...
The chemokine receptor CXCR4 plays critical roles in development, immune function, and human immunodeficiency virus type 1 (HIV-1) entry. Here we demonstrate that, like the CC-chemokine receptors CCR5 CCR2b, is posttranslationally modified by sulfation of its amino-terminal tyrosines. sulfate group at tyrosine 21 contributes substantially to ability bind ligand, stromal derived factor 1α. Tyrosine a less significant role CXCR4-dependent HIV-1 entry than CCR5-dependent In some cell lines,...
Nearly all livers transplanted into hepatitis C virus (HCV)-positive patients become infected with HCV, and 10 to 25% of reinfected develop cirrhosis within 5 years. Neutralizing monoclonal antibody could be an effective therapy for the prevention infection in a transplant setting. To pursue this treatment modality, we developed human antibodies (HuMAbs) directed against HCV E2 envelope glycoprotein assessed capacity these HuMAbs neutralize broad panel genotypes. HuMAb were generated by...
Hepatitis C virus (HCV) infection is a leading cause of liver transplantation and there an urgent need to develop therapies reduce rates HCV transplanted livers. Approved therapeutics for are poorly tolerated limited efficacy in this patient population. Human monoclonal antibody HCV1 recognizes highly-conserved linear epitope the E2 envelope glycoprotein (amino acids 412–423) neutralizes broad range genotypes. In chimpanzee model, single dose 250 mg/kg delivered 30 minutes prior infusion...
Highlights•Structure-guided affinity enhancement of a cross-reactive dengue antibody•mAb neutralizes all four serotypes with low level viral-enhancing activity•Antibody demonstrates in vivo ability to resolve symptoms severe infection•Crystal structure antibody-antigen validates the predicted designsSummaryDengue is most common vector-borne viral disease, causing nearly 400 million infections yearly. Currently there are no approved therapies. Antibody epitopes that elicit weak humoral...
Long-term organ transplant survival remains suboptimal, and life-long immunosuppression predisposes recipients to an increased risk of infection, malignancy, kidney toxicity. Promoting the regulatory arm immune system by expanding Tregs may allow minimization improve long-term graft outcomes. While low-dose IL-2 treatment can expand Tregs, it has a short half-life off-target expansion NK effector T cells, limiting its clinical applicability. Here, we designed humanized mutein with high Treg...
Severe acute respiratory syndrome (SARS) remains a significant public health concern after the epidemic in 2003. Human monoclonal antibodies (MAbs) that neutralize SARS-associated coronavirus (SARS-CoV) could provide protection for exposed individuals.Transgenic mice with human immunoglobulin genes were immunized recombinant major surface (S) glycoprotein ectodomain of SARS-CoV. Epitopes 2 neutralizing MAbs derived from these mapped and evaluated murine model SARS-CoV infection.Both bound to...
Epstein–Barr virus (EBV) establishes a life-long persistent infection in most of the human population. In peripheral blood, EBV is restricted to memory B cells that are resting and express limited genetic information. We have proposed these site long-term infection. now show tonsil genes for nuclear antigen 1 (EBNA1) (from Qp promoter), latent membrane protein (LMP1), LMP2a but do not EBNA2 or EBNA3s. This pattern gene expression has only been seen previously EBV-associated tumors such as...
Rapid allograft infection complicates liver transplantation (LT) in patients with hepatitis C virus (HCV). Pegylated interferon-α and ribavirin therapy after LT has significant toxicity limited efficacy. The effect of a human monoclonal antibody targeting the HCV E2 glycoprotein (MBL-HCV1) on viral clearance was examined randomized, double-blind, placebo-controlled pilot study infected genotype 1a undergoing LT. Subjects received 11 infusions 50 mg/kg MBL-HCV1 (n=6) or placebo (n=5)...
Engineering of antibodies for improved pharmacokinetics through enhanced binding to the neonatal Fc receptor (FcRn) has been demonstrated in transgenic mice, non-human primates and humans. Traditionally, such approaches have largely relied on random mutagenesis display formats, which fail address related critical attributes antibody, as effector functions or biophysical stability. We developed a structure- network-based framework interrogate engagement IgG with multiple receptors (FcRn, C1q,...
Significance Emerging influenza subtypes, such as the recently identified H7N9 strains, are of considerable public health concern. Although vaccines an important countermeasure, tend to be subtype- and strain-specific, that they may not widely available in event human adaptation spread unanticipated strain or subtype. Additionally, strains have demonstrated ability develop resistance existing antivirals, including oseltamivir. As such, there is a need for novel interventions can treat and/or...
In this paper we demonstrate, for the first time, that Epstein-Barr virus (EBV)-infected cells expressing lymphoblastoid growth program are present in healthy carriers of virus. Previously observed latently infected naive B tonsils only when viral replication is detected, suggesting these may represent newly cells. We have tested idea by performing a reverse transcription-PCR analysis expression latent genes (EBNA2 and EBNA3s) characteristically expressed latency program. EBNA2 regularly...
Abstract EBV is found preferentially in IgD− B cells the peripheral blood. This has led to proposal that recirculating memory cell pool site of long-lived persistent infection. In this paper we have used CD27, a newly identified specific marker for cells, test hypothesis. We show tightly restricted its expression. Less than 1 1000 infected blood are naive (IgD+, CD27−) and <1 250 IgD+ cells. Furthermore, was undetectable self-renewing CD5+ or B1 subset not been through germinal...
Immunotherapy with monoclonal antibodies (MAbs) offers safe interventions for the prevention of infection in patients after organ transplantation and treatment cancers autoimmune diseases. MAb 201 is a severe acute respiratory syndrome-associated coronavirus (SARS-CoV)-specific that prevents establishment viral replication vitro vivo when administered prophylactically. The efficacy SARS was evaluated golden Syrian hamsters, an animal model supports SARS-CoV to high levels displays...