Neutralizing Antibody Core

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Principal Investigator: Michael Scott Seaman
Organization: DANA-FARBER CANCER INST
Fiscal Year: 2024
Award: $300,463
Funding agency: National Institute of Allergy and Infectious Diseases

SUMMARY – CORE B
Neutralizing Antibody Core
Recent insights into HIV-1 Env structure and function are yielding a variety of new approaches aimed at
designing more advanced and novel immunogens for eliciting broadly neutralizing antibodies (bnAbs) through
vaccination. As improved immunogens enter detailed pre-clinical and clinical studies, it has become critical that
the in vitro assays used for making measurements of vaccine-elicited antibody responses have the ability to
distinguish incremental advances in magnitude, breadth, and durability. Core B (Neutralizing Antibody Core)
will provide standardized and validated GCLP-compliant neutralizing antibody assay services to assist
in the development and evaluation of novel mRNA-based immunogens advanced by this P01 program
and comparison of vaccine-elicited mAbs with existing and newly defined patient-derived bnAbs. These
services will provide critical data that will help guide immunogen design and strategies for vaccine formulation
and delivery proposed in Project 1 and Project 2. To accomplish these goals, we propose the following three
Specific Aims:
Specific Aim 1: Assess vaccine-elicited neutralizing antibody responses in wildtype and KI mice immunized
 with novel mRNA-based chimeric HIV-1 MPER-TM immunogens.
Specific Aim 2: Screen patient serum samples from HIV-1 infection cohorts to identify individuals with
 MPER-specific neutralizing activity for mAb cloning.
Specific Aim 3: Characterize the breadth and potency of neutralizing activity and ADCC for novel mAbs
 cloned from vaccinated animals and HIV-1 infected patients.

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