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.
