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Principal Investigator: Barton F. Haynes
Organization: DUKE UNIVERSITY
Fiscal Year: 2024
Award: $3,169,510
Funding agency: National Institute of Allergy and Infectious Diseases
Nonhuman primate studies for development of a prototype HIV vaccine that induces
broadly neutralizing antibodies
Barton Haynes, MD- PI
Sampa Santra, PhD- Co-Investigator
The Duke CHAVD has had two major breakthroughs this year in our ability to use rhesus
macaques for the study of vaccine-induced bnAb B cell lineages. The first breakthrough was
discovering the rhesus VH gene VH1-105 as the rhesus ortholog of human VH1-46 that is used
for the VH1-46 class of CD4 mimicking, CD4 binding site (CD4bs) bnAbs.1 We have recently
induced rhesus macaque VH1-105 CD4 mimicking, CD4bs bnAb precursors by immunization
with the germline targeting Env, CH505M5 G458Y GNT1-.1
The second breakthrough was discovering the rhesus gene VH7-a*01 as the ortholog of
human VH7-4-1*02, the VH used by the MPER bnAbs in HVTN 133.2 In rhesus study 181, the
MPER peptide-liposome induced VH7-a*01 antibodies with the same MPER specificity and
structure as the VH7-4-1*02 DH1317.4 bnAb. Moreover, we have demonstrated boosting of the
previously primed MPER clone with an mRNA encoding the proximal and distal MPER epitopes
(called mRNA009).
Thus, in this supplement, we are requesting support for 6 NHP studies—two MPER, two CD4
binding site, and two V3 glycan bnAb immunization regimens in macaques—each designed to
answer questions that are critical to learning the optimal ways to induce bnAbs. Most of these
new NHP studies will use recycled monkeys.
Terms: <AIDS Virus><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Antibodies><Antigenic Determinants><Antigens><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Binding Determinants><Binding Sites><Cell Lineage><Clinical Evaluation><Clinical Testing><Combining Site><Development><Distal><Doctor of Philosophy><Epitopes><GNT1><Genes><Germ Lines><Glycans><Goals><HIV><HIV Vaccine Trials Network><HIV vaccine><HIV/AIDS Vaccines><HVTN><Human><Human Immunodeficiency Viruses><Immunization><Investigators><LAV-HTLV-III><Learning><Liposomal><Liposomes><Lymphadenopathy-Associated Virus><M mulatta><M. mulatta><Macaca><Macaca mulatta><Macaque><Messenger RNA><Modern Man><Monkeys><Ortholog><Orthologous Gene><Peptides><Persons><Ph.D.><PhD><Polysaccharides><Preventative vaccine><Preventive vaccine><Prophylactic vaccine><Reactive Site><Recycling><Regimen><Research Personnel><Researchers><Rhesus><Rhesus Macaque><Rhesus Monkey><Specificity><Structure><UDP glycosyltransferase 1 family, polypeptide A1 Gene><UDP glycosyltransferase gene 1><UGT1><UGT1A><UGT1A1><UGT1A1 gene><UGT1A5><Vaccines><Virus-HIV><clinical test><design><designing><developmental><human immunodeficiency virus vaccine><immunogen><mRNA><manufacture><neutralizing antibody><non-human primate><nonhuman primate><prototype><research clinical testing><vaccination study><vaccination trial><vaccine study><vaccine trial>