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Principal Investigator: Masaru Kanekiyo
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2024
Award: $1,272,981
Funding agency: National Institute of Allergy and Infectious Diseases
Our previous work has led to the development of vaccines against respiratory syncytial virus and Zika that have reached late phase clinical testing. While we are still performing exploratory studies on immune responses to RSV in humans, our work on emerging and resurgent viruses has shifted to focus on vaccines for paramyxoviruses (primarily measles and mumps), enteroviruses (primarily enterovirus D68 and A71), herpesviruses, and coronaviruses.
Vaccines currently licensed for measles and mumps contain live-attenuated viruses. While these vaccines have had a remarkable impact of disease burden, they have several shortcomings. Live-attenuated vaccines are neutralized by maternal antibodies, dampening responses in early life and to booster vaccinations. They also have several contraindications and have been associated with adverse events that contribute to vaccine hesitancy. As a result, measles and mumps are resurgent particularly in clusters of susceptible people. We have been working on optimized vaccine antigens based on viral surface glycoproteins. Structure-based design is used to stabilize the viral fusion proteins in the prefusion conformation and co-deliver with the attachment proteins, either separately or as chimeric fusion proteins. Vaccine candidates for measles and mumps have been shown to elicit neutralizing antibodies in mice and nonhuman primates, and provide a strong boost to immunity elicited by live-attenuated vaccines.
Enterovirus D68 is a respiratory enterovirus that causes biannual respiratory illnesses in pediatric populations and has been associated with outbreaks of acute flaccid myelitis (AFM). We are designing and evaluating virus-like particle (VLP) vaccines that expresses the structural proteins of EV-D68. We have demonstrated immunogenicity and the elicitation of cross-neutralizing antibodies across multiple virus subclades following VLP immunization. We have demonstrated that passively transferred antibodies confer protection from replication of mouse-adapted virus following respiratory challenge of susceptible immunodeficient AG129 mice. We are currently testing different doses and formulations in NHP, as well as evaluating gene-based approaches to vaccination. We aim to apply the knowledge from this project to develop an enterovirus vaccine platform that can be used for vaccines against related enteroviruses such as enterovirus A7, another enterovirus associated with AFM. EV-A71 VLP elicits neutralizing antibodies and when codelivered with EV-D68 VLP, there was no reduction in the response to either virus.
We are also evaluating nanoparticle-based candidates for next-generation or pan-coronavirus vaccines, and working on the development of vaccines for herpesviruses such as Epstein-Barr virus (EBV).
Terms: <Adverse Experience><Adverse event><Airway challenge><Antigens><Attenuated><Attenuated Vaccines><Booster Immunization><Burkitt Herpesvirus><Burkitt Lymphoma Virus><Cell Surface Glycoproteins><Childhood><Chimera Protein><Chimeric Proteins><Clinical Evaluation><Clinical Research><Clinical Study><Clinical Testing><Coronaviridae><Coronavirus><Disease Outbreaks><Dose><EB virus><EBV><EV-68><EV-71><EV-A71><EV-D68><Enterovirus><Enterovirus 68><Enterovirus 71><Enterovirus A71><Enterovirus D68><Epidemic Parotitis><Epstein Barr Virus><Family Picornaviridae><Formulation><Fusion Protein><Genes><Goals><HHV-4><HHV4><Health><Herpesviridae><Herpesvirus Vaccines><Herpesviruses><Human><Human Herpesvirus 4><Immune response><Immunity><Immunization><Immunochemical Immunologic><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><Infectious Mononucleosis Virus><Knowledge><Licensing><Life><Live-attenuated Vaccine><Maternal antibody><Measles><Membrane Glycoproteins><Messenger RNA><Mice><Mice Mammals><Modern Man><Molecular Configuration><Molecular Conformation><Molecular Stereochemistry><Mumps><Murine><Mus><Outbreaks><Paramyxoviridae><Paramyxovirus><Passive Antibody Transfers><Passive Transfer of Immunity><Persons><Phase><Picornaviridae><Picornaviruses><Pneumoviridae><Pneumovirinae><Pneumovirus><Population><Predisposition><Proteins><Respiratory syncytial virus><Rubeola><Secondary Immunization><Structural Protein><Structure><Surface Glycoproteins><Susceptibility><T-Cells><T-Lymphocyte><Testing><Vaccination><Vaccine Antigen><Vaccine Design><Vaccine Research><Vaccines><Viral><Viral Fusion Proteins><Virus><Virus-like particle><Work><ZIKA><acute flaccid myelitis><adaptive immune response><attenuate><attenuates><booster vaccination><burden of disease><burden of illness><candidate identification><clinical development><clinical test><conformation><conformational><conformational state><conformationally><conformations><corona virus><design><designing><develop a vaccine><develop vaccines><development of a vaccine><disease burden><epidemic parotiditis><evaluate vaccines><herpes virus><hesitant to vaccination><host response><hypoimmunity><immune deficiency><immune system response><immunodeficiency><immunogen><immunogenicity><immunoresponse><live vaccine><live vaccines><mRNA><morbilli><nano particle><nano-sized particle><nanoparticle><nanosized particle><neutralizing antibody><neutralizing vaccine><new vaccines><next generation><next generation vaccines><non-human primate><nonhuman primate><novel vaccines><pan CoV vaccine><pan coronavirus vaccine><panCoV vaccine><pancoronavirus vaccine><paramyxovirus vaccine><pediatric><pre-clinical study><preclinical study><research clinical testing><respiratory><respiratory challenge><response><thymus derived lymphocyte><universal CoV vaccine><universal coronavirus vaccine><vaccination hesitancy><vaccine candidate><vaccine development><vaccine evaluation><vaccine hesitancy><vaccine hesitant><vaccine platform><vaccine screening><vaccine testing><vaccine-related research><virus-like nanoparticles><viruslike particle>