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Principal Investigator: Barton F. Haynes
Organization: DUKE UNIVERSITY
Fiscal Year: 2024
Award: $3,192,992
Funding agency: National Institute of Allergy and Infectious Diseases
Supplement request to DAIDS to Manufacture an mRNA/LNP encoding an HIV envelope
designed to bind and stimulate multiple V2 Apex broadly neutralizing antibody B cell
lineages
Barton Haynes, CHAVD PI
Thomas Denny, Investigator, manufacture team
This request is to produce GMP an mRNA immunogen that encodes an Env that binds to multiple
V2 apex broadly neutralizing antibody (bnAb) naïve B cell precursors that are required for the
acquisition of bnAb breadth against the V2 apex of HIV-1. This mRNA encodes a gp150
immunogen (OPT4.R189T “shielded”) targeting 6 V2 apex UCAs and will be tested both as a
prime and as an immunofocusing boost for induction of V2 apex bnAbs. The immunogen that this
mRNA will be compared with as a prime is a similar protein, OPT4 “unshielded” Env-ferritin
nanoparticle (NP), that targets 9 V2 apex UCAs. Moreover, since the mRNA OPT4.R189T
“shielded” Env can boost on-track V2 apex bnAbs in monkeys, it will be tested as a boosting
immunogen with the protein prime, OPT4 “unshielded” Env-ferritin nanoparticle (NP), that is also
requested to be manufactured in a separate CHAVD manufacturing supplement request. What
follows below is the rationale for requesting the production of the OPT4.R189T “shielded” Env
gp150 mRNA/LNP under GMP conditions in this Y6 CHAVD supplement.
Specific Aim 1. Demonstration batch production and analytical development of candidate
mRNAs.
Specific Aim 2. Deliver final drug substances and drug products for toxicology studies and
clinical testing
Specific Aim 3. Develop and deliver a regulatory strategy to enable Phase I proof of
concept clinical studies.
Terms: <AIDS Virus><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Antigens><Apical><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Binding><Cell Lineage><Clinical Evaluation><Clinical Research><Clinical Study><Clinical Testing><Development><Drugs><Early-Stage Clinical Trials><Ferritin><Goals><HIV><HIV Vaccine Trials Network><HIV envelope><HIV envelope protein><HIV-1><HIV-I><HIV1><HVTN><Human Immunodeficiency Virus Type 1><Human Immunodeficiency Viruses><Human immunodeficiency virus 1><Investigators><LAV-HTLV-III><Lymphadenopathy-Associated Virus><Medication><Messenger RNA><Molecular Interaction><Monkeys><Persons><Pharmaceutical Preparations><Phase><Phase 1 Clinical Trials><Phase I Clinical Trials><Preventative vaccine><Preventive vaccine><Production><Prophylactic vaccine><Proteins><Research Personnel><Researchers><Site><Testing><Toxicology><Virus-HIV><clinical test><design><designing><develop a vaccine><develop vaccines><development of a vaccine><developmental><drug/agent><immunogen><mRNA><manufacture><nano particle><nano-sized particle><nanoparticle><nanosized particle><neutralizing antibody><phase I protocol><research clinical testing><vaccine development>