A5046329566- Influenza Virus Research Studies
- Respiratory viral infections research
- Escherichia coli research studies
- Viral gastroenteritis research and epidemiology
- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- Bacteriophages and microbial interactions
- Animal Virus Infections Studies
- COVID-19 Clinical Research Studies
- Bacterial Genetics and Biotechnology
- Antimicrobial Resistance in Staphylococcus
- RNA and protein synthesis mechanisms
- Tracheal and airway disorders
- Genomics and Phylogenetic Studies
- Glycosylation and Glycoproteins Research
- Biochemical and Structural Characterization
- Research on Leishmaniasis Studies
- SARS-CoV-2 detection and testing
- Carbohydrate Chemistry and Synthesis
- Viral Infections and Outbreaks Research
- Long-Term Effects of COVID-19
- COVID-19 epidemiological studies
- Virus-based gene therapy research
- interferon and immune responses
- Bacterial Identification and Susceptibility Testing
Center for Biologics Evaluation and Research
2017-2024
Virginia Commonwealth University
2015-2017
Understanding antibody epitope diversity and affinity generated by SARS-CoV-2 spike antigens in rabbits can aid COVID-19 vaccine development.
Hospitalized COVID-19 patients often present with a large spectrum of clinical symptoms. There is critical need to better understand the immune responses SARS-CoV-2 that lead either resolution or exacerbation disease. Here, we examine longitudinal plasma samples from hospitalized differential outcome. We perform immune-repertoire analysis including cytokine, hACE2-receptor inhibition, neutralization titers, antibody epitope repertoire, kinetics, isotype and affinity maturation against...
Several next-generation (universal) influenza vaccines and broadly neutralizing antibodies (bNAbs) are in clinical development. Some of these mediate inhibitions virus replication at the postentry stage or use Fc-dependent mechanisms. Nonneutralizing have potential to enhancement viral infection disease. In current study, two monoclonal (MAbs) 72/8 69/1, enhanced respiratory disease (ERD) mice following H3N2 challenge by demonstrating increased lung pathology changes cytokine/chemokine...
Limited knowledge exists on immune markers associated with disease severity or recovery in patients coronavirus 2019 (COVID-19). Here, we elucidated longitudinal evolution of SARS-CoV-2 antibody repertoire acute COVID-19. Differential kinetics was observed for immunoglobulin M (IgM)/IgG/IgA epitope diversity, binding, and affinity maturation "severe" versus "mild" COVID-19 patients. IgG profile demonstrated immunodominant antigenic sequences encompassing fusion peptide receptor binding...
Staphylococcus aureus pathogenicity islands (SaPIs), such as SaPI1, exploit specific helper bacteriophages, like 80α, for their high frequency mobilization, a process termed ‘molecular piracy’. SaPI1 redirects the helper’s assembly pathway to form small capsids that can only accommodate smaller genome, but not complete phage genome. encodes two proteins, CpmA and CpmB, are responsible this size redirection. We have determined structures of 80α procapsids near-atomic resolution by...
Abstract Currently, only Palivizumab and Nirsevimab that target the respiratory syncytical virus (RSV) fusion protein are licensed for pre-treatment of infants. Glycoprotein-targeting antibodies may also provide protection against RSV. In this study, we generate monoclonal from mice immunized with G proteins RSV-A2 RSV-B1 strains. These recognize six unique antigenic classes (G0-G5). None anti-G neutralize or in vitro. challenged either line 19 F RSV-B1, one day after treatment antibodies,...
Abstract In current study, we evaluated the safety and protective efficacy of recombinant unglycosylated RSV G protein ectodomain produced in E. coli (in presence absence oil-in-water adjuvant) a preclinical susceptible cotton rat challenge model compared to formaldehyde inactivated (FI-RSV) live experimental infection. The adjuvanted vaccine induced robust neutralization antibody responses comparable those generated by Importantly, significantly reduced viral loads both lungs nose at early...
Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract disease in infants. Previously, we elucidated antibody repertoire following primary RSV infection Whole genome-fragment phage display libraries (GFPDL) expressing linear and conformational epitopes from bound 100-fold more phages within attachment protein (G) infection. The G-reactive spanned N- C-termini G ectodomain, addition to central conserved domain (CCD). In current study, examined contribution antigenic...
Although viral-based influenza vaccines contain neuraminidase (NA or N) antigens from the recommended seasonal strains, NA is not extensively evaluated like hemagglutinin (H) during strain selection process. Here, we compared antigenicity of NAs recently H1N1 (2010-2021 seasons) and H3N2 (2015-2021 vaccine strains viruses that circulated between September 2019 December 2020. The was by measuring ferret antisera titers provide 50% inhibition activity in an enzyme-linked lectin assay. Our...
Virions are a common antigen source for many viral vaccines. One limitation to using virions is that the abundance determined by content of each protein in virus. This caveat especially applies viral-based influenza vaccines where low neuraminidase (NA) surface remains bottleneck improving NA antibody response. Our systematic analysis recent H1N1 vaccine antigens demonstrates hemagglutinin (HA) ratio can be improved exchanging backbone internal genes, segment encoding polymerase PB1 subunit....
For several decades, it has been proposed that influenza vaccines could be supplemented with recombinant neuraminidase (rNA) to improve efficacy. However, some key questions for manufacturing stable and immunogenic rNAs remain answered.
The leishmanin skin test was used for almost a century to detect exposure and immunity Leishmania, the causative agent of leishmaniasis, major neglected tropical disease. Due lack antigen intradermal injection, is no longer available. As leishmaniasis control programs are advancing new vaccines entering clinical trials, it essential re-introduce test. Here we establish Leishmania donovani strain describe production, under Good Laboratory Practice conditions, soluble induce in animal models...
In the tailed bacteriophages, DNA is packaged into spherical procapsids, leading to expansion angular, thin-walled mature capsids. many cases, this maturation accompanied by cleavage of major capsid protein (CP) and other capsid-associated proteins, including scaffolding (SP) that serves as a chaperone for assembly process. Staphylococcus aureus bacteriophage 80α capable high frequency mobilization mobile genetic elements called S. pathogenicity islands (SaPIs), such SaPI1. SaPI1 redirects...
ABSTRACT Multiple vaccine candidates against SARS-CoV-2 based on viral spike protein are under development. However, there is limited information the quality of antibody response generated following vaccination by these modalities. To better understand induced protein-based vaccines, we immunized rabbits with various antigens: S-ectodomain (S1+S2) (aa 16-1213), which lacks cytoplasmic and transmembrane domains (CT-TM), S1 domain 16-685), receptor-binding (RBD) 319-541), S2 686-1213 as...
Broadly neutralizing monoclonal antibodies (bNAbs) against conserved domains in the influenza hemagglutinin are clinical trials. Several next generation vaccines designed to elicit such bNAbs also development. One of common features isolated is use restricted IgVH repertoire. More than 80% stem-targeting express IgVH1-69, which may indicate genetic constraints on evolution antibodies. In current study, we evaluated a panel virus comparison with HIV-1 MAb 4E10 and anti-RSV Palivizumab...
Sialidases or neuraminidases are sialic-acid-cleaving enzymes that expressed by a broad spectrum of organisms, including pathogens. In nature, sialic acids monosaccharides with diverse structural variations, but the lack novel probes has made it difficult to determine how acid modifications impact recognition sialidases. Here, we used chemoenzymatic synthon strategy generate set α2–3- and α2–6-linked sialoside contain 7-N-acetyl 7,9-di-N-acetyl as structure mimics for those containing less...
Most seasonal influenza vaccines are produced using hemagglutinin (HA) surface antigens from inactivated virions. However, virions thought to be a suboptimal source for the less abundant neuraminidase (NA) antigen, which is also protective against severe disease. Here, we demonstrate that compatible with two modern approaches improving antibody responses NA. Using DBA/2J mouse model, show strong infection-induced NA inhibitory (NAI) only achieved by high dose immunizations of virions, likely...
Limited knowledge exists on the quality of polyclonal antibody response generated following Ebola virus (EBOV) infection compared with vaccination. Polyclonal repertoire in plasma EBOV survivors was ChAd3-MVA prime-boost human Higher binding and affinity to GP observed vaccinated that correlated neutralization. Surprisingly, a predominant IgM after vaccination, whereas demonstrated IgG-dominant response. induced more diverse epitope A strong antigenic sites fusion peptide another highly...
Reverse genetics (RG) systems have been instrumental for determining the molecular aspects of viral replication, pathogenesis, and development therapeutics. Here, we demonstrate that genes encoding influenza surface antigens hemagglutinin neuraminidase varying stability when cloned into a common RG plasmid transformed Escherichia coli. Using GFP as reporter, E. coli expresses target in at low levels. Incorporating lac operators or transcriptional terminator reduced expression stabilized to...
ABSTRACT Supplementing influenza vaccines with recombinant neuraminidase (rNA) remains a promising approach for improving the suboptimal efficacy. However, correlations among rNA designs, properties, and protection have not been systematically investigated. Here, we performed comparative analysis of several rNAs produced from different construct designs using baculovirus/insect cell system. The were designed tetramerization motifs NA domains recent H1N1 vaccine strain (A/Brisbane/02/2018)...
CHARACTERIZATION OF THE INTERACTIONS BETWEEN STAPHYLOCOCCAL PHAGE 80 ALPHA SCAFFOLD AND CAPSID PROTEINS
ABSTRACT Most seasonal influenza vaccines are produced using hemagglutinin (HA) surface antigens from inactivated virions. However, virions thought to be a suboptimal source for the less abundant NA antigen, which is also protective against severe disease. Here, we demonstrate that compatible with two modern approaches improving antibody responses. Using DBA/2J mouse model, confirmed strong infection-induced inhibitory (NAI) responses only achieved by high dose immunizations of virions,...
Journal Article Staphylococcus aureus Pathogenicity Islands: Hijackers on the Bacteriophage Assembly Pathway. Get access Terje Dokland, Dokland Department of Microbiology, University Alabama at Birmingham, AL, U.S.A Search for other works by this author on: Oxford Academic Google Scholar James L Kizziah, Kizziah Altaira D Dearborn, Dearborn National Institute Arthritis and Musculoskeletal Skin Diseases, Bethesda, MD, Keith A Manning, Manning Erin Wall, Wall Microbiology Immunology, Virginia...