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Principal Investigator: Aleksandra Elzbieta Sikora
Organization: OREGON STATE UNIVERSITY
Fiscal Year: 2024
Award: $737,096
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><Address><Adjuvant><Alum Adjuvant><Antibiotic Resistance><Antibodies><Antibody Response><Antigen Targeting><Antigens><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Binding><Bio-Informatics><Bioinformatics><Blocking Antibodies><Blood Neutrophil><Blood Plasma><Blood Polymorphonuclear Neutrophil><Blood Serum><COVID-19 S protein><COVID-19 prevention><COVID-19 spike><COVID-19 spike glycoprotein><COVID-19 spike protein><Capsid Proteins><Categories><Cell Body><Cells><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><Immunological response><Immunology><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><N. gonorrhoeae vaccine><Neisseria gonorrhea><Neisseria gonorrhoeae><Neisseria gonorrhoeae vaccine><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><SARS-CoV-2 S protein><SARS-CoV-2 spike><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 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><Vaccines><Vagina><Venereal Diseases><Venereal Disorders><Venereal Infections><Viral Antigens><Viral Coat Proteins><Viral Outer Coat Protein><Virus-like particle><alum><aluminum sulfate><anti-microbial><antibiotic drug resistance><antibiotic resistant><antigen-specific T cells><antimicrobial><bactericidal><bactericide><clearance rate><clinical development><cohort><comparative><complementation><conformation><conformational><conformational state><conformationally><conformations><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><determine efficacy><develop a vaccine><develop vaccines><development of a vaccine><efficacy analysis><efficacy assessment><efficacy determination><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 response to vaccination><immune response to vaccines><immune system response><immunogen><immunogenicity><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 coronavirus disease 2019><priority pathogen><protein folding><racial minority><receptor binding><receptor bound><research and development><resistant><response><self assembly><sexual minority><sexually acquired infection><spike proteins on SARS-CoV-2><statistics><vaccine against N. gonorrhoeae><vaccine against Neisseria gonorrhoeae><vaccine associated immune response><vaccine candidate><vaccine candidates for Neisseria gonorrhoeae><vaccine development><vaccine evaluation><vaccine immune response><vaccine immunogenicity><vaccine induced immune response><vaccine platform><vaccine screening><vaccine testing><vaccinology><vaginal mucosa><virus antigen><virus-like nanoparticles><viruslike particle><wart virus>