A5010907671- Herpesvirus Infections and Treatments
- Immunotherapy and Immune Responses
- Cytomegalovirus and herpesvirus research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Diabetes and associated disorders
- Immune Response and Inflammation
- Virus-based gene therapy research
- interferon and immune responses
- SARS-CoV-2 and COVID-19 Research
- Poxvirus research and outbreaks
- Animal Virus Infections Studies
- vaccines and immunoinformatics approaches
- Xenotransplantation and immune response
- Pancreatic function and diabetes
- Diabetes Management and Research
- RNA Interference and Gene Delivery
- Celiac Disease Research and Management
- Ocular Surface and Contact Lens
- Monoclonal and Polyclonal Antibodies Research
- Systemic Lupus Erythematosus Research
- Viral-associated cancers and disorders
- Toxoplasma gondii Research Studies
- Liver Diseases and Immunity
- Atherosclerosis and Cardiovascular Diseases
University of California, Irvine
2012-2025
University of Pretoria
2022-2023
King Fahd Medical City
2011-2022
Université Mohammed VI des Sciences de la Santé
2017-2018
King Saud bin Abdulaziz University for Health Sciences
2012
University of California, Irvine Medical Center
2009-2011
National Eye Institute
2009
Montreal Children's Hospital
2002-2006
McGill University
2002-2006
European Union
1999
Since early 2020, several SARS-CoV-2 variants of concern (VOCs) continue to emerge, evading waning antibody mediated immunity produced by the current Spike-alone based COVID-19 vaccines. This caused a prolonged and persistent pandemic that is going enter its fifth year. Thus, need remains for innovative next generation vaccines would incorporate protective Spike-derived B-cell epitopes resist immune evasion. Towards goal, in this study we (i) Screened sequences Spike among many VOCs...
Type 1 diabetes results from autoimmune destruction of the insulin-producing pancreatic β-cells. Evidence our laboratory and others has suggested that IDDM2 locus determines susceptibility by modulating levels insulin expression in thymus: diabetes-protective class III alleles at a repeat polymorphism upstream gene are associated with higher than predisposing I. To directly demonstrate effect thymic on insulin-specific autoreactive T-cell selection, we have established mouse model which...
Abstract Exogenous glucocorticoid hormones are widely used as therapeutical agents, whereas endogenous glucocorticoids may act physiological immunosuppressants involved in the control of immune and inflammatory responses. The optimal activation T lymphocytes requires two distinct signals: major histocompatibility complex‐restricted presentation antigen an additional co‐stimulatory signal provided by antigen‐presenting cells. There is ample evidence that, among cells able to present antigen,...
Abstract Over the last two decades, there have been three deadly human outbreaks of coronaviruses (CoVs) caused by SARS-CoV, MERS-CoV, and SARS-CoV-2, which has current COVID-19 global pandemic. All CoVs originated from bats transmitted to humans via various intermediate animal reservoirs. It remains highly possible that other COVID pandemics will emerge in coming years yet another spillover a bat-derived SARS-like coronavirus (SL-CoV) into humans. Determining Ag B cells, CD4+ CD8+ T cell...
ABSTRACT The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) is the only HSV-1 gene abundantly expressed throughout latency. LAT null mutants have a significantly reduced reactivation phenotype. LAT's antiapoptosis activity major factor involved in supporting wild-type During latency, some ganglionic neurons are surrounded by CD8 T cells, and it has been proposed that these cells help maintain latency suppressing viral reactivations. Surprisingly, despite injection of...
Abstract Evidence obtained from both animal models and humans suggests that T cells specific for HSV-1 HSV-2 glycoprotein D (gD) contribute to protective immunity against herpes infection. However, knowledge of gD-specific human cell responses is limited CD4+ epitopes, with no CD8+ epitopes identified date. In this study, we screened the gD amino acid sequence HLA-A*0201-restricted using several predictive computational algorithms 10 high probability epitopes. Synthetic peptides...
We introduced a novel humanized HLA-A*0201 transgenic (HLA Tg) rabbit model to assess the protective efficacy of human CD8(+) T cell epitope-based vaccine against primary ocular herpes infection and disease. Each three immunodominant peptide epitopes from HSV-1 glycoprotein D (gD(53-61), gD(70-78), gD(278-286)) were joined with promiscuous CD4(+) epitope (gD(49-82)) construct separate pairs CD4-CD8 peptides. pair was then covalently linked an N(epsilon)-palmitoyl-lysine residue via...
Following ocular herpes simplex virus 1 (HSV-1) infection of C57BL/6 mice, HSV-specific (HSV-gB(498-505) tetramer(+)) CD8(+) T cells are induced, selectively retained in latently infected trigeminal ganglia (TG), and appear to decrease HSV-1 reactivation. The latency-associated transcript (LAT) gene, the only viral gene that is abundantly transcribed during latency, increases Previously we found latency with strain McKrae-derived viruses, more total TG resident CD8 expressed markers...
Background: Nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNPs) have emerged as a promising vaccine strategy, especially for COVID-19. While the LNPs protect from degradation and efficiently deliver to antigen-presenting cells, effect of composition on immunogenicity protective efficacy mRNA/LNP vaccines is not well characterized. Studies using platform largely focused nucleic acid cargo with less attention paid LNP vehicle. Whether biophysical properties impact performance...
The identification of "asymptomatic" (i.e., protective) epitopes recognized by T cells from herpes simplex virus (HSV)-seropositive healthy individuals is a prerequisite for an effective vaccine. Using the PepScan epitope mapping strategy, library 179 potential peptide (15-mers overlapping 10 amino acids) was identified HSV type 1 (HSV-1) glycoprotein B (gB), antigen that induces protective immunity in both animal models and humans. Eighteen groups (G1 to G18) adjacent peptides each were...
Evidence from C57BL/6 mice suggests that CD8(+) T cells, specific to the immunodominant HSV-1 glycoprotein B (gB) H-2(b)-restricted epitope (gB498-505), protect against ocular herpes infection and disease. However, possible role of HLA-restricted gB epitopes, in protective immunity seen HSV-1-seropositive asymptomatic (ASYMP) healthy individuals (who have never had clinical herpes) remains be determined. In this study, we used multiple prediction algorithms identify 10 potential...
ABSTRACT Herpes simplex virus 1 (HSV-1) and HSV-2 are medically significant pathogens. The development of an effective HSV vaccine remains a global public health priority. HSV-1 immunodominant “asymptomatic” antigens (ID-A-Ags), which strongly recognized by B T cells from seropositive healthy asymptomatic individuals, may be critical to included in immunotherapeutic vaccine. In contrast, “symptomatic” (ID-S-Ags) exacerbate herpetic disease therefore must excluded any the present study,...
Routine serodiagnosis of herpes simplex virus (HSV) infections is currently performed using recombinant glycoprotein G (gG) antigens from 1 (HSV-1) and HSV-2. This a single-antigen test has only one diagnostic application. Relatively little known about HSV antigenicity at the proteome-wide level, full potential mining antibody repertoire to identify with other useful properties candidate vaccine yet be realized. To this end we produced HSV-1 -2 proteome microarrays in Escherichia coli probed...
Abstract HSV type 1 (HSV-1) is a prevalent human pathogen that infects >3.72 billion individuals worldwide and can cause potentially blinding recurrent corneal herpetic disease. HSV-1 establishes latency within sensory neurons of trigeminal ganglia (TG), TG-resident CD8+ T cells play critical role in preventing its reactivation. The repertoire, phenotype, function protective are unknown. Bolstering the apparent feeble numbers TG remains challenge for immunotherapeutic strategies. In...
We created and tested multi-epitope DNA or protein vaccines with TLR4 ligand emulsion adjuvant (gluco glucopyranosyl lipid in a stable [GLA-SE]) for their ability to protect against Toxoplasma gondii HLA transgenic mice. Our constructs each included 5 of our best down-selected CD8+ T cell–eliciting epitopes, universal CD4+ helper lymphocyte epitope (PADRE), secretory signal, all arranged optimal MHC-I presentation. Their capacity elicit immune protective responses was studied using...
Both topical ocular and intranasal immunizations have been reported to stimulate the mucosal immune system (OMIS) systemic system. Nasolacrimal ducts (NLDs) are connecting bridges between OMIS nasal cavity-associated lymphoid tissue (NALT). These drain ocularly administrated solutions into inferior meatus of nose reach NALT. Inversely, NLDs also intranasally surface eye thus OMIS. This unique anatomical connection NALT systems provoked us test whether immunologically interdependent. In this...
Abstract Targeting of the mucosal immune system genital tract with subunit vaccines has failed to induce potent and durable local CD8+ T cell immunity, which is crucial for protection against many sexually transmitted viral pathogens, including HSV type 2 (HSV-2), causes herpes. In this study, we aimed investigate potential a novel lipopeptide/adenovirus 5 (Lipo/rAdv5) prime/boost vaccine induction immunity protect female from The lipopeptide rAdv5 express immunodominant HSV-2 epitope...