Document text
Principal Investigator: Gregory Allan Smith
Organization: THYREOS, INC
Fiscal Year: 2023
Award: $297,493
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY
There is an unmet need for a herpes simplex virus (HSV) vaccine. We propose to
develop a live-attenuated HSV-2 vaccine based on our R2 technology platform. R2
vaccines show unprecedented safety and efficacy in animal models, and offer
antigenicity superior to subunit/mRNA and single-round vaccine designs. R2 vaccines
are also the first live-attenuated alphaherpesvirus vaccines that lack neuroinvasive
potential, and thereby are incapable of establishing life-long infections in the nervous
system. In phase I of this fast-track STTR application, we propose to: (i) produce a HSV-
2 self-excising infectious clone of a low-passage clinical isolate, (ii) use the clone to
produce a HSV-2 R2 recombinant, and (iii) characterize the R2 vaccine in culture side by
side with our existing HSV-1 R2 vaccine candidate. In phase II, the HSV-2 R2 vaccine
will be tested for safety, immunogenicity, and efficacy in mice and guinea pigs. This work
will provide the foundation to advance product development to clinical trials.
Terms: <0-4 weeks old><Ab-dependent cellular cytotoxicity><Ablation><Abscission><Animal Model><Animal Models and Related Studies><Antibodies><Attenuated><Attenuated Vaccines><Award><Axonal Transport><Axoplasmic Transport><BAC clone><BACs><Bacterial Artificial Chromosomes><Binding><Birth><Bleb><Blister><Body Tissues><Brain Inflammation><Bulla><Bullous Lesion><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><CNS Diseases><CNS disorder><Cavia><Cell Culture Techniques><Central Nervous System Diseases><Central Nervous System Disorders><Children's Hospital><Clinical><Clinical Trials><Code><Coding System><Congenital herpes simplex><Congenital herpes simplex infection><DNA Recombination><Dedications><Development><Development and Research><Disease><Disorder><Early-Stage Clinical Trials><Encephalitis><Excision><Extirpation><Failure><Foundations><Fred Hutchinson Cancer Research Center><Gene Expression><Genes><Genetic><Genetic Alteration><Genetic Change><Genetic Recombination><Genetic defect><Genital><Genital Organs><Genitalia><Goals><Guinea Pigs><Guinea Pigs Mammals><HHV-2><HHV2><HSV Vaccines><HSV infection in neonates><HSV-1><HSV-2><HSV1><HSV2><Herpes Simplex Type 1><Herpes Simplex Virus 1><Herpes Simplex Virus 2><Herpes Simplex Virus Type 1><Herpes Simplex Virus Type 2><Herpes Simplex Virus Vaccines><Herpesvirus 1><Herpesvirus 2 (alpha), Human><Herpesvirus progenitalis><Human (alpha) herpes virus 2><Human Herpesvirus 2><Human herpes simplex virus type 2><Immune response><Immunological response><Infection><Infectious Agent><Invaded><Life><Live-attenuated Vaccine><Marker Vaccines><Marketing><Measures><Medical center><Messenger RNA><Methods><Mice><Mice Mammals><Modeling><Molecular Interaction><Monitor><Mucosa><Mucosal Tissue><Mucous Membrane><Murine><Mus><Mutate><Mutation><Neonatal herpes simplex><Nervous System><Neurologic><Neurologic Body System><Neurologic Deficit><Neurologic Organ System><Neurological><Newborn Infant><Newborns><Pain><Painful><Parturition><Pediatric Hospitals><Persons><Phase><Phase 1 Clinical Trials><Phase I Clinical Trials><Phenotype><Population><Position><Positioning Attribute><Preparation><Proteins><R & D><R&D><Recombinants><Recombination><Recurrence><Recurrent><Removal><STTR><Safety><Serial Passage><Serology><Sexual Transmission><Sexually Transmitted Diseases><Sexually Transmitted Disorder><Sexually Transmitted Infection><Side><Simplexvirus Vaccines><Small Business Technology Transfer Research><Staining method><Stains><Surgical Removal><T cell response><T4 Cells><T4 Lymphocytes><T8 Cells><T8 Lymphocytes><Technology><Testing><Tissues><Transmission><Universities><Vaccine Design><Vaccines><Vagina><Vaginal><Validation><Venereal Diseases><Venereal Disorders><Venereal Infections><Vertical Disease Transmission><Vesication><Virulence><Virus><Virus Replication><Work><adaptive immune response><antibody dependent cell mediated cytotoxicity><antibody dependent cytotoxicity><antibody mediated cellular cytotoxicity><antibody-dependent cell cytotoxicity><antibody-dependent cellular cytotoxicity><antibody-dependent cellular phagocytosis><antibody-mediated cytotoxicity><attenuate><attenuates><attenuation><cell culture><cell cultures><congenital herpes simplex virus infection><cytokine><design><designing><develop a vaccine><develop vaccines><development of a vaccine><developmental><genital infection><genome mutation><guinea pig model><herpes simplex i><herpes simplex ii><herpes simplex-1><host response><human alphaherpesvirus 2><immune system response><immunogenicity><immunoresponse><infectious organism><latent infection><live vaccine><live vaccines><mRNA><model of animal><mother to child transmission><mouse model><murine model><mutant><neonatal HSV infection><neonatal herpes><neonate><neutralizing antibody><newborn child><newborn children><next generation><phase I protocol><pre-clinical><preclinical><preparations><product development><prototype><research and development><resection><safety testing><sexually transmitted><technology platform><technology system><transmission process><vaccine candidate><vaccine development><vaccine efficacy><validations><viral multiplication><viral replication><virus multiplication>