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Principal Investigator: Barton F. Haynes
Organization: DUKE UNIVERSITY
Fiscal Year: 2020
Award: $629,514
Funding agency: National Institute of Allergy and Infectious Diseases
The overall goal of the Animal Models Core is to support all programs of the IPCAVD by performing
immunization studies in CH58 unmutated common ancestor (UCA) VH + VL knock-in (KI) mice and rhesus
macaques, with ALVAC-C vCP2438 prime and modified mRNA encoding trivalent mosaic gp120s for induction
of polyfunctional anti-HIV-1 non-neutralizing antibodies (NNAbs) (Project 1, Aims 2 and 3), and by overseeing
toxicity studies using CGMP clinical trials material (CTM) mRNAs in collaboration with Project 2. This work will
be facilitated by recent innovative advances made in a number of complementing areas, including the
development of novel SHIV constructs expressing transmitted/founder HIV-1 envelopes, well-tolerated
adjuvants that substantially increase the immunogenicity of HIV-1 envelope protein immunogens and induce T
follicular helper cell (Tfh) responses, technology for reproducibly generating envelope-specific monoclonal
antibodies from immunized macaques, and use of the new CH58 VH and VL knock-in mouse that expresses
one of the NNAb ADCC-mediating antibodies from RV144, CH58 V2 antibody. The Specific Aims of this
Animal Models Core will include:
Aim 1. Perform immunization studies in CH58 unmutated common ancestor (UCA) homozygous
(hom)/heterozygous (het) VH + VL knock-in (KI) mice ALVAC-C vCP2438 prime and modified mRNA
encoding trivalent mosaic gp120s in Project 1, Aim 2.
Aim 2. Perform immunization studies with ALVAC-C vCP2438 prime and boosting with and boosting
with ALVAC-C plus modified mRNA encoding trivalent mosaic gp120s mRNAs in rhesus macaques
(RMs) (Project 1, Aim 3).
Aim 3. Perform immunization studies in CH58 UCA hom/het VH + VL KI mice to confirm CGMP clinical
trials materials immunogenicity, and oversee toxicity studies of ALVAC-C + CGMP mRNAs in
collaboration with Project 2.
Terms: <AIDS Virus><ALVAC><ALVAC Canarypox Vector><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Adjuvant><Animal Model><Animal Models and Related Studies><Antibodies><Antigens><Area><Assay><Bioassay><Biologic Assays><Biological Assay><Biometrics><Biometry><Biostatistics><Clinical Treatment Moab><Clinical Trials><Collaborations><Complement><Complement Proteins><Data><Development><Envelope Protein><Goals><HIV><HIV immunization><HIV-1><HIV-1 vaccine><HIV-I><HIV1><HIV1 vaccine><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><Mediating><Messenger RNA><Mice><Mice Mammals><Monoclonal Antibodies><Mosaicism><Murine><Mus><Nucleosides><Proteins><Rhesus Macaque><Rhesus Monkey><SHIV><Statistical Data Analyses><Statistical Data Analysis><Statistical Data Interpretation><Technology><Toxic effect><Toxicities><Translating><Virus-HIV><Work><ZIKA><data management><developmental><env Antigens><env Gene Products><env Polyproteins><env Protein><expectation><humanized mice><humanized mouse><immunogen><immunogenic><immunogenicity><in vivo><innovate><innovation><innovative><knockin mice><mAbs><mRNA><model of animal><model organism><mosaic disorders><non-human primate><nonhuman primate><novel><programs><response><simian HIV><simian human immunodeficiency virus><statistical analysis><vector>