Animal Core

NIH Pandemic-Era Grants

Pandemic Era Grants

2021

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Principal Investigator: Barton F. Haynes
Organization: DUKE UNIVERSITY
Fiscal Year: 2021
Award: $2
Funding agency: National Institute of Allergy and Infectious Diseases

The overall goals of the Animal Models Core is to support all programs of the IPCAVD by performing
immunization studies in DH270 unmutated common ancestor (UCA) VH + VL knock-in (KI) mice with V3- Man9
glycopeptide primes and modified mRNA boosts (Project 1, Aim 2), by performing immunization studies with
the optimized V3-Man9 glycopeptide and modified mRNA regimen in rhesus macaques (Project 1, Aim 3),
and by performing immunization studies in DH270 UCA VH + VL KI mice and overseeing toxicity studies of
CGMP clinical trials material (CTM) mRNAs in collaboration with Project 2. The Specific Aims of this Animal
Models Core will include:
Aim 1. Perform immunization studies in DH270 unmutated common ancestor (UCA) VH + VL knock-in
(KI) mice with Man9-V3 glycopeptides and modified mRNAs in Project 1, Aim 2.
Aim 2. Perform immunization with the optimized Man9-V3 glycopeptide and modified mRNA regimen in
rhesus macaques (Project 1, Aim 3).
Aim 3. Perform immunization studies in DH270 UCA VH + VL KI mice and overseeing toxicity studies of
CGMP clinical trials material (CTM) mRNAs in collaboration with
This project will advance nucleoside-modified mRNA as a platform for HIV-1 Env immunization and establish
its immunogenicity in humanized mice and NHPs. Preliminary studies have demonstrated that the
extraordinary immunogenicity of modified mRNAs in mice translates to rhesus macaques in the setting of Zika
and HIV immunizations. Thus, we anticipate that mRNA will be both cost-effective and highly immunogenic and
therefore have the potential to be transformative to the HIV vaccine field as a vector.

Terms: <AIDS Virus><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Adjuvant><Animal Model><Animal Models and Related Studies><Animals><Antigens><Area><Assay><B blood cells><B cell><B cells><B-Cell Epitopes><B-Cells><B-Lymphocyte Epitopes><B-Lymphocytes><B-cell><Bioassay><Biologic Assays><Biological Assay><Cell Lineage><Clinical Treatment Moab><Clinical Trials><Collaborations><Complement><Complement Proteins><Data><Development><Envelope Protein><Glycans><Glycopeptides><Goals><HIV><HIV immunization><HIV vaccine><HIV-1><HIV-I><HIV/AIDS Vaccines><HIV1><Helper Cells><Helper T-Cells><Helper T-Lymphocytes><Helper-Inducer T-Cells><Helper-Inducer T-Lymphocyte><Human Immunodeficiency Virus Type 1><Human Immunodeficiency Viruses><Human immunodeficiency virus 1><Immunization><Immunize><Immunologic Sensitization><Immunologic Stimulation><Immunological Sensitization><Immunological Stimulation><Immunostimulation><Inducer Cells><Inducer T-Lymphocytes><KI mice><Knock-in Mouse><LAV-HTLV-III><Lymphadenopathy-Associated Virus><M mulatta><M. mulatta><Macaca><Macaca mulatta><Macaque><Messenger RNA><Mice><Mice Mammals><Monoclonal Antibodies><Murine><Mus><Nucleosides><Polysaccharides><Proteins><Regimen><Rhesus Macaque><Rhesus Monkey><SHIV><Statistical Data Analyses><Statistical Data Analysis><Statistical Data Interpretation><Technology><Testing><Toxic effect><Toxicities><Translating><Virus-HIV><Work><ZIKA><cost effective><data management><developmental><env Antigens><env Gene Products><env Polyproteins><env Protein><expectation><human immunodeficiency virus vaccine><humanized mice><humanized mouse><immunogen><immunogenic><immunogenicity><in vivo><knockin mice><mAbs><mRNA><model of animal><model organism><mouse model><murine model><neutralizing antibody><non-human primate><nonhuman primate><novel><programs><response><simian HIV><simian human immunodeficiency virus><statistical analysis><vector>