Vaccine Research and Development for Endemic, Emerging, and Resurgent Viruses

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Principal Investigator: Masaru  Kanekiyo
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2022
Award: $955,000
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 some exploratory studies on vaccine-elicited immunity following RSV vaccination, the work of the Respiratory Viruses Core has shifted to focus on vaccines for paramyxoviruses (primarily measles and mumps) and enteroviruses (primarily enterovirus D68 and A71).

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 testing in nonhuman primates is underway.

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. A VLP vaccine candidate is currently being tested in nonhuman primates, and development at the Vaccine Production Program has been initiated. We aim to apply the knowledge from this project to develop an enterovirus vaccine platform that can be used for vaccines against related enteroviruses.

Terms: <Adverse Experience><Adverse event><Airway challenge><Antigens><Attenuated><Attenuated Vaccines><Booster Immunization><Cell Surface Glycoproteins><Childhood><Chimera Protein><Chimeric Proteins><Clinical Evaluation><Clinical Research><Clinical Study><Clinical Testing><Coronaviridae><Coronavirus><Development and Research><Disease Outbreaks><Enterovirus><Enterovirus 68><Enterovirus D68><Epidemic Parotitis><Family Picornaviridae><Fusion Protein><Genes><Goals><Health><Herpesviridae><Herpesviruses><Human><Immunity><Immunization><Immunochemical Immunologic><Immunologic><Immunologic Sensitization><Immunologic Stimulation><Immunological><Immunological Sensitization><Immunological Stimulation><Immunologically><Immunologics><Immunostimulation><Knowledge><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><Proteins><R & D><R&D><Respiratory syncytial virus><Rubeola><Secondary Immunization><Structural Protein><Structure><Surface Glycoproteins><T-Cells><T-Lymphocyte><Testing><Vaccination><Vaccine Antigen><Vaccine Design><Vaccine Production><Vaccine Research><Vaccines><Viral><Viral Fusion Proteins><Virus><Virus-like particle><Work><ZIKA><acute flaccid myelitis><adaptive immune response><base><booster vaccination><burden of disease><burden of illness><clinical development><clinical test><conformation><conformational state><corona virus><design><designing><develop a vaccine><develop vaccines><development of a vaccine><disease burden><epidemic parotiditis><evaluate vaccines><herpes virus><hesitant to vaccination><immunogen><immunogenicity><live vaccine><live vaccines><mRNA><morbilli><nano particle><nano-sized particle><nanoparticle><nanosized particle><neutralizing antibody><neutralizing vaccine><new vaccines><next generation vaccines><non-human primate><nonhuman primate><novel vaccines><paramyxovirus vaccine><pediatric><pre-clinical study><preclinical study><primate development><produce vaccines><programs><research and development><research clinical testing><respiratory><respiratory challenge><respiratory virus><response><thymus derived lymphocyte><vaccination hesitancy><vaccine candidate><vaccine development><vaccine evaluation><vaccine hesitancy><vaccine hesitant><vaccine platform><vaccine screening><vaccine testing><virus core><virus-like nanoparticles><viruslike particle><years of life lost to disability><years of life lost to disease>