TFH-TARGETING GENETIC ADJUVANTS TO PROMOTE DURABLE ANTI-INFLUENZA STEM ANTIBODIES IN OLDER ADULTS.
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Principal Investigator: KENTNER SINGLETON Organization: TENDEL THERAPIES INC. Fiscal Year: 2023 Award: $599,980 Funding agency: National Institute of Allergy and Infectious Diseases The project is focused on progressing BiTar-s3, a vaccine adjuvant agent. The project will develop a vaccine that targets HA stem epitopes shared across many flu-A strains, thereby addressing the difficulty of eliciting heterosubtypic neutralizing antibodies (nAb) against influenza. Specifically, the project’s aims are constructing immunogens fused to the BiTar-s3 adjuvant, to select a lead vaccine candidate; test safety and immunogenicity of the s3-adjuvanted candidate in mice; and test safety and immunogenicity of the s3-adjuvanted and unadjuvanted vaccine candidate in aged rhesus macaques. Methods will include testing expression and immunoreactivity with anti-HA antibodies of targeted candidate immunogens, engineering the selected immunogen into a high-capacity adenovector, testing the ability of s3 to drive anti-HA stem Tfh and antibody responses, testing safety of the s3-adjuvanted and unadjuvanted vaccines in aged rhesus macaques, evaluating adaptive immune responses, and examining the mechanisms of s3 adjuvant activity in germinal centers. Terms: <Ad vector><Address><Adenoviral Vector><Adenoviridae><Adenovirus Vector><Adenoviruses><Adjuvant><Antibodies><Antibody Response><Antigenic Determinants><Antigens><Binding Determinants><CD3><CD3 Antigens><CD3 Complex><CD3 molecule><Contractor><Elderly><Engineering><Epitopes><Genetic><Germinal Center><Grippe><Hemagglutinin><Human><Influenza><Influenza Vaccines><Lead><Licensing><M mulatta><M. mulatta><Macaca mulatta><Messenger RNA><Methods><Mice><Mice Mammals><Modern Man><Murine><Mus><NIH Vaccine Research Center><OKT3 antigen><Pb element><Rhesus Macaque><Rhesus Monkey><Safety><Serotyping><Structure of germinal center of lymph node><T3 Antigens><T3 Complex><T3 molecule><Testing><Transfer Agreement><Vaccine Adjuvant><Vaccine Research><Vaccines><Validation><adaptive immune response><adeno vector><adenovector><advanced age><aged><anti-flu><anti-influenza><antiflu><data exchange><data transfer><data transmission><develop a vaccine><develop vaccines><development of a vaccine><elders><flu><flu vaccine><flu virus vaccine><geriatric><heavy metal Pb><heavy metal lead><immunogen><immunogenicity><immunoreactivity><influenza virus vaccine><late life><later life><lipid based nanoparticle><lipid nanoparticle><mRNA><neutralizing antibody><older adult><older person><safety testing><senior citizen><stem><vaccine against flu><vaccine against influenza><vaccine candidate><vaccine development><vaccine platform><vaccine-related research><validations><vector>