A5072931108- HIV Research and Treatment
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- SARS-CoV-2 and COVID-19 Research
- Viral gastroenteritis research and epidemiology
- Influenza Virus Research Studies
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- T-cell and B-cell Immunology
- Hepatitis B Virus Studies
- SARS-CoV-2 detection and testing
- vaccines and immunoinformatics approaches
- HIV/AIDS Research and Interventions
- Virology and Viral Diseases
- Animal Virus Infections Studies
- Cytomegalovirus and herpesvirus research
- Monoclonal and Polyclonal Antibodies Research
- COVID-19 Clinical Research Studies
- Mosquito-borne diseases and control
- Herpesvirus Infections and Treatments
- Respiratory viral infections research
- Viral Infections and Vectors
- HIV/AIDS drug development and treatment
- Transgenic Plants and Applications
- Immune Response and Inflammation
University of Washington
2016-2025
Oregon National Primate Research Center
2020-2023
Alpine Immune Sciences (United States)
2020-2021
Seattle University
2019
Gabrielle’s Angel Foundation for Cancer Research
2015
May Institute
2015
Fred Hutch Cancer Center
2015
Office of the Director
2015
Albany Medical Center Hospital
2009-2012
University of Pittsburgh
2001-2012
Plasmid DNAs expressing influenza virus hemagglutinin glycoproteins have been tested for their ability to raise protective immunity against lethal challenges of the same subtype. In trials using two inoculations from 50 300 micrograms purified DNA in saline, 67-95% test mice and 25-63% chickens protected a challenge. Parenteral routes inoculation that achieved good protection included intramuscular intravenous injections. Successful mucosal vaccination drops administered nares or trachea. By...
A safe, effective, and scalable vaccine is needed to halt the ongoing SARS-CoV-2 pandemic. We describe structure-based design of self-assembling protein nanoparticle immunogens that elicit potent protective antibody responses against in mice. The vaccines display 60 spike receptor-binding domains (RBDs) a highly immunogenic array induce neutralizing titers 10-fold higher than prefusion-stabilized despite 5-fold lower dose. Antibodies elicited by RBD nanoparticles target multiple distinct...
The coronavirus disease 2019 (COVID-19) pandemic, caused by infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is having a deleterious impact on health services and global economy, highlighting urgent need for an effective vaccine. Such vaccine would to rapidly confer protection after one or two doses be manufactured using components suitable scale up. Here, we developed
We developed a de novo protein design strategy to swiftly engineer decoys for neutralizing pathogens that exploit extracellular host proteins infect the cell. Our pipeline allowed design, validation, and optimization of human angiotensin-converting enzyme 2 (hACE2) neutralize severe acute respiratory syndrome coronavirus (SARS-CoV-2). The best monovalent decoy, CTC-445.2, bound with low nanomolar affinity high specificity receptor-binding domain (RBD) spike protein. Cryo-electron microscopy...
Abstract The observed role of CTL in the containment AIDS virus replication suggests that an effective HIV vaccine will be required to generate strong responses. Because epitope-based vaccines offer several potential advantages for inducing strong, multispecific responses, we tested ability DNA prime/modified vaccinia Ankara (MVA) boost induce responses against a single SIVgag epitope. As assessed using both 51Cr release assays and tetramer staining vitro stimulated PBMC, vaccinations...
ABSTRACT Producing a prophylactic vaccine for human immunodeficiency virus (HIV) has proven to be challenge. Most biological isolates of HIV are difficult neutralize, so that conventional subunit-based antibody-inducing vaccines unlikely very effective. In the rhesus macaque model, some protection was afforded by DNA/recombinant viral vector vaccines. However, these studies used as challenge SHIV-89.6P, which is neutralizable, making it determine whether observed due cellular immunity,...
A human growth hormone expression construct was delivered intracellularly into the abdominal skin of mice by particle bombardment-mediated gene transfer. Using this technology, in vivo delivery antigen-encoding vectors affixed to gold microprojectiles results de novo antigen production target and development specific antibody responses. In study, we examined contribution various parameters resultant protein related The highest levels both were correlated with epidermis while deliveries...
A New Twist on RNA Vaccines There are several strategies to elicit immunity with an vaccine; they all involve coaxing the host cell replicate and translate exogenous encoding vacc...
Cytokine release syndrome (CRS), commonly known as cytokine storm, is an acute systemic inflammatory response that a significant global health threat. Interleukin-6 (IL-6) and interleukin-1 (IL-1) are key pro-inflammatory cytokines involved in CRS hence critical therapeutic targets. Current antagonists, such tocilizumab anakinra, target IL-6R/IL-1R but have limitations due to their long half-life anti-inflammatory effects, making them less suitable for or localized treatments. Here we...
The potential for eliciting humoral and cytotoxic T lymphocyte (CTL) responses to HIV-1 gp120 by gene gunbased DNA immunization in mice was examined. We speculated that the induction of de novo antigen production epidermis BALB/c following particle bombardment-based delivery would result both MHC class I- II-mediated presentation elicitation CTL antibody responses, respectively. Following epidermal microgram quantities an expression plasmid, resulted appearance I-restricted, CD8+ responses....
Despite mass public health efforts, the SARS-CoV2 pandemic continues as of late 2021 with resurgent case numbers in many parts world. The emergence variants concern (VoCs) and evidence that existing vaccines were designed to protect from original strains SARS-CoV-2 may have reduced potency for protection infection against these VoC is driving continued development second-generation can multiple VoC. In this report, we evaluated an alphavirus-based replicating RNA vaccine expressing Spike...
Immunization with mosaic-8b (nanoparticles presenting 8 SARS-like betacoronavirus [sarbecovirus] receptor-binding domains [RBDs]) elicits more broadly cross-reactive antibodies than homotypic SARS-CoV-2 RBD-only nanoparticles and protects against sarbecoviruses. To investigate original antigenic sin (OAS) effects on efficacy, we evaluated the of prior COVID-19 vaccinations in non-human primates mice anti-sarbecovirus responses elicited by mosaic-8b, admix-8b (8 homotypics), or immunizations,...
Programmed cell death protein 1 (PD-1) is an immune checkpoint marker commonly expressed on memory T cells and enriched in latently HIV-infected CD4+ cells. We engineered anti-PD-1 chimeric antigen receptor (CAR) to assess the impact of PD-1 depletion viral reservoirs rebound dynamics SIVmac239-infected rhesus macaques (RMs). Adoptive transfer CAR was done 2 SIV-naive 4 SIV-infected RMs antiretroviral therapy (ART). In 3 6 RMs, expanded persisted for up 100 days concomitant with PD-1+ blood...
Naked DNA vaccines expressing the prM and E genes of two tick-borne flaviviruses, Russian spring summer encephalitis (RSSE) virus Central European (CEE) were evaluated in mice. The administered by particle bombardment DNA-coated gold beads Accell gene gun inoculation. Two immunizations 0.5 to 1 microg RSSE or CEE constructs/dose, delivered at 4-week intervals, elicited cross-reactive antibodies detectable enzyme-linked immunosorbent assay high-titer neutralizing virus. Cross-challenge...
ABSTRACT An effective vaccine against human immunodeficiency virus (HIV) should protect mucosal transmission of genetically divergent isolates. As a safe alternative to live attenuated vaccines, the immunogenicity and protective efficacy DNA containing simian (SIV) strain 17E-Fr (SIV/17E-Fr) gag-pol-env was analyzed in rhesus macaques. Significant levels cytotoxic T lymphocytes (CTL), but low undetectable serum antibody responses, were observed following multiple immunizations. SIV-specific...
Given the current difficulties generating vaccine-induced neutralizing antibodies to human immunodeficiency virus (HIV), focus of vaccine community has shifted toward creating cytotoxic-T-lymphocyte (CTL)-based vaccines. Recent reports CTL-based trials in macaques challenged with simian/human SHIV-89.6P have supported notion that such vaccines can ameliorate course disease. However, almost all these studies included Env as an immunogen and since is sensitive it difficult determine...