A5091303440- Influenza Virus Research Studies
- Immune Response and Inflammation
- Respiratory viral infections research
- Monoclonal and Polyclonal Antibodies Research
- Escherichia coli research studies
- Viral gastroenteritis research and epidemiology
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Glycosylation and Glycoproteins Research
- Animal Disease Management and Epidemiology
- SARS-CoV-2 and COVID-19 Research
- vaccines and immunoinformatics approaches
- Bacterial Infections and Vaccines
- Streptococcal Infections and Treatments
- Immune Cell Function and Interaction
- Salmonella and Campylobacter epidemiology
- Pneumonia and Respiratory Infections
- Clostridium difficile and Clostridium perfringens research
- Bacteriophages and microbial interactions
- Advanced Drug Delivery Systems
- Infective Endocarditis Diagnosis and Management
- Travel-related health issues
- Animal Virus Infections Studies
- Antimicrobial Resistance in Staphylococcus
- Neuroinflammation and Neurodegeneration Mechanisms
GlaxoSmithKline (United States)
2019-2025
GlaxoSmithKline (Canada)
2010-2014
GlaxoSmithKline (United Kingdom)
2011
Intel (United States)
2001
Walter Reed Army Institute of Research
1988-1998
Indiana University – Purdue University Indianapolis
1997
University Medical Center
1997
Uniformed Services University of the Health Sciences
1997
National Institutes of Health
1989-1992
National Cancer Institute
1986-1992
RNA vaccines have demonstrated efficacy against SARS-CoV-2 in humans, and the technology is being leveraged for rapid emergency response. In this report, we assessed immunogenicity and, first time, toxicity, biodistribution, protective preclinical models of a two-dose self-amplifying messenger (SAM) vaccine, encoding prefusion-stabilized spike antigen Wuhan-Hu-1 strain delivered by lipid nanoparticles (LNPs). mice, one immunization with SAM vaccine elicited robust spike-specific antibody...
Abstract We recently reported that application of cholera toxin (CT) to the skin results in transcutaneous immunization and induces a systemic Ab response both CT coadministered Ags. In this paper, we demonstrate antitoxin IgG IgA Abs sera, lung washes, stool samples from immunized mice as well broad spectrum subclasses (IgG1, IgG2a, IgG2b, IgG3) sera. Mice with by route exhibited significant protection intranasal challenge lethal dose CT. Thus, clinically relevant immunity against mucosal...
The neuraminidase inhibitor oseltamivir is currently used for treatment of patients infected with the pandemic A/H1N1 (pH1N1) influenza virus, although drug-resistant mutants can emerge rapidly and possibly be transmitted. We describe characteristics a pair oseltamivir-resistant oseltamivir-susceptible pH1N1 clinical isolates that differed by single change (H274Y) in protein. Viral fitness was assessed vitro determining replication kinetics MDCK alpha2,6 cells vivo performing experimental...
Seasonal influenza virus vaccines are generally effective at preventing disease, but need to be well matched circulating strains for maximum benefit. Influenza viruses constantly undergo antigenic changes because of their high mutation rate in the immunodominant haemagglutinin (HA) head domain, which necessitates annual re-formulation and re-vaccination continuing protection. In case pandemic outbreaks, new produced quickly distributed. Novel that redirect immune response towards more...
ABSTRACT We studied the safety and immunogenicity of a Shigella flexneri 2a vaccine comprising native S. lipopolysaccharide (LPS) complexed to meningococcal outer membrane proteins—proteosomes—in normal, healthy adults. A two-dose series immunizations was given by intranasal spray, doses 0.1, 0.4, 1.0, 1.5 mg (based on protein) were in dose-escalating design. The generally well tolerated. most common reactions included rhinorrhea nasal stuffiness, which clearly dose related ( P ≤ 0.05)....
A murine pulmonary model was used to study the mucosal immune response Shigella flexneri serotype 2a infection. Inoculation of BALB/cJ mice with shigellae via intranasal route resulted in bacterial invasion bronchial and alveolar epithelia concomitant development acute suppurative bronchiolitis subsequent lethal pneumonia. The pathology lesions resembled colitis that characterizes shigellosis humans primates. Significant protection against a dose S. observed previously infected two sublethal...
ABSTRACT Amino acid substitutions at residue I223 of the neuraminidase (NA) protein have been identified in 2009 pandemic influenza (pH1N1) variants with altered susceptibilities to NA inhibitors (NAIs). We used reverse genetics and site-directed mutagenesis generate recombinant A/Québec/144147/09 pH1N1 wild-type virus (WT) five (I223R, I223V, H275Y, I223V-H275Y, I223R-H275Y) mutants. A fluorimetry-based assay was determine 50% inhibitory concentrations (IC 50 s) oseltamivir, zanamivir,...
Abstract The high variation of the influenza virus hemagglutinin (HA), particularly its immunodominant head epitopes, makes it necessary to reformulate seasonal vaccines every year. Novel that redirect immune response toward conserved epitopes HA stalk domain should afford broad and durable protection. Sequential immunization with chimeric HAs (cHAs) express same distinct exotic heads has been shown elicit levels broadly cross-reactive Abs. In current mouse studies, we tested this strategy...
The RSVPreF3-AS01 vaccine, containing the respiratory syncytial virus (RSV) prefusion F protein and AS01 adjuvant, was previously shown to boost neutralization responses against historical RSV strains be efficacious in preventing RSV-associated lower tract diseases older adults. Although is highly conserved, variation does exist between strains. Here, we characterized variations major viral antigenic sites among contemporary sequences when compared with RSVPreF3 showed that, adults, broadly...
Mice immunized intransally or intragastrically with proteosome vaccines containing either Shigella sonnei S. flexneri 2a lipopolysaccharide were protected against lethal pneumonia caused by homologous organisms in an experimental murine intranasal challenge model of infection. Histopathological analysis demonstrated that immunization also the progressive lesions resulting from invasion pulmonary mucosa sonnei. These data show mucosal proteosome-lipopolysaccharide can protect bacterial and...
The Ig kappa complex locus of inbred mice found on chromosome 6 contains one constant (C kappa), five joining (J and 100 to 300 variable (V kappa) exons spans an estimated 500 2000 kbp DNA. V are organized into groups highly homologous coding regions (approximately bp) separated by approximately 10 intervening sequence. A group from 1 30 or more (exon refers uninterrupted region DNA which is capable encoding all part gene) that can be detected with specific probes in conjunction restriction...
We tested 49 BALB/c antilysozyme mAb from seven intervals during the immune response to lysozyme for patterns of specificity and avidity. found that antibody epitopes in composite covered at least 80% surface, their overlap suggest a continuum potential epitopes. Previously observed regional specificities, which emerged different times response, were more discretely defined late antibodies, when majority could be assigned one three functionally nonoverlapping complementation groups. The area...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern challenge the efficacy approved vaccines, emphasizing need for updated spike antigens. Here, we use an evolutionary-based design aimed at boosting protein expression levels S-2P and improving immunogenic outcomes in mice. Thirty-six prototype antigens were generated silico 15 produced biochemical analysis. S2D14, which contains 20 computationally designed mutations within S2 domain a rationally engineered D614G...
Influenza A/H3N2 viruses have caused the most severe epidemics since 1968 despite current immunization programs with inactivated vaccines. We undertook a side-by-side preclinical evaluation of different adjuvants (Alum, AS03, and Protollin) routes administration (intramuscular [i.m.] intranasal [i.n.]) for assessing their effect on immunogenicity cross-reactivity split vaccines (A/H3N2/New York/55/2004). Humoral T cell-mediated immune responses against homologous virus heterologous drifted...
During the 2009-2010 influenza pandemic, an adjuvanted, dose-sparing vaccine was recommended for most Canadians. We hypothesize that differences exist in responses to AS03-adjuvanted, low antigen (Ag) dose versus unadjuvanted, full-dose vaccines. investigated relationship between Ag and oil-in-water emulsion Adjuvant System AS03. BALB/c mice received two IM doses of AS03A or AS03B with exaggerated dilutions A/Uruguay/716/2007 H3N2 split virion Ag. Immune were assessed three weeks after...
Abstract Broad protection against diverse influenza viruses can be conferred by broadly neutralizing antibodies (bnAbs) targeting a conserved site on the hemagglutinin (HA) stem domain. However, low immunogenicity of this antigenic region hinders robust induction such antibodies. Here, we showcase structure-based immunogen design strategy focusing surface mimicry sites. By leveraging structural definition epitope, apply computational protein to develop epitope mimetics focus immune response...
Introduction A Proteosome-adjuvanted trivalent inactivated influenza vaccine (P-TIV) administered intra-nasally was shown to be safe, well tolerated and immunogenic in both systemic mucosal compartments, effective at preventing illness associated with evidence of infection. Methods In two separate studies using the human viral challenge model, subjects were selected immunologically naive A/Panama/2007/1999 (H3N2) virus then dosed via nasal spray one three regimens P-TIV or placebo. One...
Abstract Highly pathogenic avian influenza (HPAI) A(H5Nx) viruses continue to pose a pandemic threat. US national vaccine stockpiles are cornerstone of the preparedness plans. However, continual genetic and antigenic divergence requires development effective vaccination strategies using stockpiled vaccines adjuvants for preparedness. Human sera collected from healthy adults who received either homologous (2 doses AS03 A -adjuvanted A/turkey/Turkey/1/2005, A/Turkey), or heterologous (primed...
Licensed influenza virus vaccines target the head domain of hemagglutinin (HA) glycoprotein which undergoes constant antigenic drift. The highly conserved HA stalk is an attractive to increase immunologic breadth required for universal vaccines. We tested hypothesis that immunization with a pandemic vaccine boosts pre-existing anti-stalk antibodies. used chimeric cH6/1, full length H2 and H18 antigens in ELISA measure antibodies recipients participating clinical trials A/H1N1, A/H5N1 A/H9N2...