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Principal Investigator: Aleksandra Elzbieta Sikora
Organization: OREGON STATE UNIVERSITY
Fiscal Year: 2022
Award: $703,672
Funding agency: National Institute of Allergy and Infectious Diseases
ABSTRACT
Neisseria gonorrhoeae (Ng), the gram-negative bacterium responsible for the sexually transmitted infection
gonorrhea, is categorized as a high-priority pathogen for research and development efforts. In the US, over 50%
of Ng isolates are resistant to at least one antimicrobial and the CDC has ranked Ng as one of the top 5 urgent
antibiotic resistant threats. Gonorrhea outcomes are especially devastating in sexual, gender, racial, and ethnic
minorities and resource-limited countries. Ng’s “superbug” status, its high morbidity, and the serious health and
psychological impacts of gonorrhea necessitate vaccine development. To address the urgent need for an
effective and safe vaccine against gonorrhea, we propose to use a powerful Virus-like-Particle (VLP) vaccine
platform with a highly effective split-protein conjugation system to deliver promising Ng antigens (Ag) as full-
length and natively folded proteins. We selected for this proposal six promising lipoproteins based on their: 1)
exceptional conservation in >5K sequenced Ng isolates worldwide; 2) surface-exposure; 3) ability to elicit
bactericidal antibodies (Abs); 4) expression in geographically and temporally diverse Ng strains, during different
in vitro conditions and Ng infection in the gonorrhea mouse model; and 5) important functions in Ng pathogenesis
and physiology. We will: 1) Design and produce antigen-VLP formulations; 2) Identify Ag-VLP and adjuvant
combinations that generate robust immune responses; and 3) Evaluate efficacy of promising vaccines and
elucidate the immune correlates of protection. Our approach presents conceptual and technical innovations in
the gonorrhea vaccine field by pioneering VLP-display of conserved, full-length Ng lipoproteins, which will be
comparatively assessed for efficacy and potential mechanisms of protection.
Terms: <2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><7S Gamma Globulin><Ab response><Address><Adjuvant><Alum Adjuvant><Antibiotic Resistance><Antibodies><Antibody Formation><Antibody Production><Antigen Targeting><Antigens><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Binding><Bio-Informatics><Bioinformatics><Blood Neutrophil><Blood Plasma><Blood Polymorphonuclear Neutrophil><Blood Serum><CDC><COVID-19 S protein><COVID-19 prevention><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID19 S protein><COVID19 prevention><COVID19 spike glycoprotein><COVID19 spike protein><Capsid Proteins><Cell Body><Cells><Centers for Disease Control><Centers for Disease Control and Prevention><Centers for Disease Control and Prevention (U.S.)><Clinical><Clinical Trials><Coat Proteins><Complement><Complement Proteins><Complex><Control Groups><Country><Coupling><Data><Development and Research><Disease><Disorder><Ensure><FDA approved><Female><Fimbriae Proteins><Formulation><Funding><Future><Geography><Germinal Center><Goals><Gonococcal Infection><Gonococcus><Gonorrhea><Gram-Negative Bacteria><HPV><HPV Vaccine><Health><Helper Cells><Helper T-Cells><Helper T-Lymphocytes><Helper-Inducer T-Cells><Helper-Inducer T-Lymphocyte><Human><Human Papilloma Virus><Human Papilloma Virus Vaccine><Human Papillomavirus><Human papillomavirus Vaccine><IgA><IgG><Immune><Immune Globulins><Immune response><Immune system><Immunes><Immunization><Immunize><Immunoglobulin A><Immunoglobulin G><Immunoglobulins><Immunologic Sensitization><Immunologic Stimulation><Immunological Sensitization><Immunological Stimulation><Immunological response><Immunology><Immunostimulation><In Vitro><Incidence><Inducer Cells><Inducer T-Lymphocytes><Infection><Infectious Human Wart Virus><Knock-out><Knockout><Lead><Length><Lipoproteins><Lymphatic Tissue><Lymphoid Tissue><Marrow Neutrophil><Measures><Memory><Metabolic Clearance Rate><Mice><Mice Mammals><Mining><Modern Man><Molecular Configuration><Molecular Conformation><Molecular Interaction><Molecular Stereochemistry><Morbidity><Morbidity - disease rate><Mucosa><Mucosal Tissue><Mucous Membrane><Multi-Drug Resistance><Multidrug Resistance><Multiple Drug Resistance><Multiple Drug Resistant><Murine><Mus><N gonorrhea><N gonorrhoeae><N. gonorrhea><N. gonorrhoeae><Neisseria gonorrhea><Neisseria gonorrhoeae><Neutrophilic Granulocyte><Neutrophilic Leukocyte><Outcome><Particulate><Pathogenesis><Pb element><Physiology><Pili Structural Proteins><Pilin><Plasma><Plasma Serum><Polymorphonuclear Cell><Polymorphonuclear Leukocytes><Polymorphonuclear Neutrophils><Protein Subunits><Proteins><Proteomics><Psychological Impact><Public Health><R & D><R&D><Recombinants><Reproductive Health><Research><Research Resources><Resistance><Resistance to Multi-drug><Resistance to Multidrug><Resistance to Multiple Drug><Resistance to antibiotics><Resistant to Multiple Drug><Resistant to antibiotics><Resistant to multi-drug><Resistant to multidrug><Resources><Reticuloendothelial System, Serum, Plasma><SARS-CoV-2 S protein><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV2 S protein><SARS-CoV2 spike glycoprotein><SARS-CoV2 spike protein><Serum><Severe acute respiratory syndrome coronavirus 2 S protein><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Sexually Transmitted Diseases><Sexually Transmitted Disorder><Sexually Transmitted Infection><Standardization><Structure of germinal center of lymph node><Subunit Vaccines><Superbug><Surface><System><T cell response><United States Centers for Disease Control><United States Centers for Disease Control and Prevention><Vaccines><Vagina><Vaginal><Venereal Diseases><Venereal Disorders><Venereal Infections><Viral Antigens><Viral Coat Proteins><Viral Outer Coat Protein><Virus-like particle><allergic/immunologic body system><allergic/immunologic organ system><alum><aluminum sulfate><anti-microbial><antibiotic drug resistance><antibiotic resistant><antibody biosynthesis><antigen-specific T cells><antimicrobial><bactericidal><bactericide><base><clearance rate><clinical development><cohort><comparative><conformation><conformational state><coronavirus disease 2019 S protein><coronavirus disease 2019 prevention><coronavirus disease 2019 spike glycoprotein><coronavirus disease 2019 spike protein><coronavirus disease-19 prevention><cost effective><density><design><designing><develop a vaccine><develop vaccines><development of a vaccine><efficacy analysis><efficacy assessment><efficacy evaluation><efficacy examination><efficacy study><ethnic minority><evaluate efficacy><evaluate vaccines><examine efficacy><gender minority><gonorrhea vaccine><heavy metal Pb><heavy metal lead><his6 tag><host response><immune system response><immunogen><immunogenicity><immunoglobulin biosynthesis><immunoresponse><innovate><innovation><innovative><male><mouse model><multi-drug resistant><multidrug resistant><murine model><neonatal health><neutrophil><new vaccines><newborn health><next generation vaccines><novel vaccines><pre-clinical efficacy><pre-clinical study><preclinical efficacy><preclinical study><prevent COVID-19><prevent COVID19><prevent coronavirus disease 2019><priority pathogen><protein folding><racial minority><receptor binding><receptor bound><research and development><resistant><response><self assembly><sexual minority><statistics><vaccine candidate><vaccine development><vaccine evaluation><vaccine platform><vaccine screening><vaccine testing><vaccinology><vaginal mucosa><virus antigen><virus-like nanoparticles><viruslike particle><wart virus>