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.