# Nab evolution in humans and RMs > **NIH NIH P01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $689,877 ## Abstract Summary Project 2 will test the hypothesis that despite their complexity and tortuous nature, the somatic evolution of B cells to bNAb activity is deterministic. That is, generation of bNAbs will follow a common and reproducible pathway(s) of clonal evolution that is reproducible in response to SHIV infections with chimeric viruses bearing Envs from primary or transmitted/founder HIV-1 strains. This question is crucial to the potential utility of all HIV- 1 lineage design vaccine strategies: if bNAb responses are unique accidents of somatic evolution, lineage design vaccines based on the response of a single, rare human subject are unlikely to be generally applicable. In contrast, if clonal evolution to bNAb activity in individual humans and in RMs follows a shared evolutionary trajectory guided by serial antigen exposure, lineage design vaccines that guide clonal evolution will be potentially effective in many vaccinees. Project 2 comprises three Specific Aims. In Aims 1 and 2, we propose to characterize the germinal center (GC) and memory B-cell (Bmem) responses in RMs identically infected in Project 1 with molecularly cloned SHIV-CH848 (or other V3-glycan targeting SHIV) or SHIV-CAP256 (or other V1V2 targeting SHIV). The principal goal of these studies is to determine whether the NAb and bNAb responses of different outbred RMs are substantially similar in a SHIV Env-specific manner. In collaboration with Cores B and C, we will define the specificity, avidity, neutralization capacity, and somatic genetics of NAb and bNAb B cells elicited by SHIV infection. Similar B-cell responses, as defined by specificity and V(D)J selection, will demonstrate that deterministic factors control the somatic evolution of NAb and bNAb B cells elicited by SHIV infection. In Aim 3, we propose to follow the B cell responses of SHIV infected RMs that have been vaccinated by Project 3. In the event that any vaccine does not confer full and complete resistance to infection, Aim 3 will allow us to characterize the vaccine's effects on clonal selection, affinity maturation, and changes in the frequencies of NAb and bNAb B-cell clones elicited by SHIV infection. This information will allow Project 3 to “tune” vaccine strategies for maximal effect. 1 ## Key facts - **NIH application ID:** 10117177 - **Project number:** 5P01AI131251-05 - **Recipient organization:** UNIVERSITY OF PENNSYLVANIA - **Principal Investigator:** GARNETT H KELSOE - **Activity code:** P01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2021 - **Award amount:** $689,877 - **Award type:** 5 - **Project period:** 2017-03-07 → 2022-05-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10117177 ## Citation > US National Institutes of Health, RePORTER application 10117177, Nab evolution in humans and RMs (5P01AI131251-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10117177. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*