HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees.

Dr. Shen is an Associate Director and Deputy of the Laboratory for HIV and COVID-19 Vaccine Research & Development in the Department of Surgery, Division of Surgical Sciences at Duke University Medical Center. Her research interest focuses on the humoral immune response following virus infection or vaccination. During the past decade, she has worked intensively on the specificity and breadth of binding antibody responses against HIV.

Dr. Shen’s team developed assays and analytical tools for a peptide microarray assay for finely mapping of HIV-1 cross-subtype linear epitopes targeted by antibody responses in human specimens as well as animal models, and adopted a multiplex binding antibody assay for evaluating binding antibody responses. With these technologies, her team evaluated various clinical HIV-1 vaccine studies and NHP studies. Building upon the data generated by her team and other collaborators, Dr. Shen works with bioinformatics and biostatistics personnel on deciphering immune correlates in both human clinical trials and nonhuman primate studies. During the COVID-19 pandemic, her team expanded their research to SARS-COV-2 antibody responses.

In 2021, Dr. Shen became the Deputy Director of the Laboratory for HIV and COVID-19 Vaccine Research & Development, alongside Laboratory Director Dr. Montefiori.  The laboratory established a lentivirus-based pseudovirus SARS-CoV-2 neutralization assay that has been FDA-approved. The laboratory is assessing neutralizing antibody responses for multiple phase 3 COVID-19 vaccine trials. In addition to supporting clinical trials, the lab has a strong focus on characterizing SARS-CoV-2 variants for their neutralizing susceptibility and potential to escape from vaccine-elicited immune responses.

Meanwhile, Dr. Shen’s team remains highly active in HIV-1 vaccine research, evaluating neutralizing responses in preclinical and clinical HIV vaccine trials as a core laboratory for multiple networks including the HIV Vaccine Trials Network (HVTN), the Collaboration for AIDS Vaccine Discovery (CAVD) funded by Bill & Melinda Gates Foundation, as well as the NIH Nonhuman Primate Core Humoral Immunology Laboratory for AIDS Vaccine which Dr. Shen directs.

Research Interests. 

The Alam laboratory’s primary research is focused on understanding the biophysical properties of antigen-antibody binding and the molecular events of early B cell activation using the HIV-1 broadly neutralizing antibody (bnAb) lineage models. We are studying how HIV-1 Envelope proteins of varying affinities are sensed by B cells expressing HIV-1 bnAbs or their germline antigen receptors and initiate early signaling events for their activation. In the long-term these studies will facilitate design and pre-selection of immunogens for testing in animal models and accelerate HIV-1 vaccine development.
Current research include the following NIAID-funded projects   

Antigen recognition and activation of B cell antigen receptors with the specificity of HIV-1 broadly neutralizing antibodies. This project involves elucidating the early events on the B cell surface following antigen (Ag) engagement of the B cell antigen receptor (BCR) and to provide an assessment of the in vivo potential of an Ag to drive B cell activation. We are performing biophysical interactions analyses and using high-resolution microscopy to define the physico-chemical properties of BCR-Ag interactions that govern signaling and activation thresholds for BCR triggering and the BCR endocytic function in antigen internalization. The overall objective of these studies is to bridge the quantitative biophysical and membrane dynamics measurements of Ag-BCR interactions to ex-vivo and in-vivo B cell activation. This NIAID-funded research is a collaboration with co-investigators Professor Michael Reth (University of Freiburg, Germany) and Dr. Laurent Verkoczy (San Diego Biomedical Research Institute, CA).  

Dr. Montefiori is Professor and Director of the Laboratory for HIV and COVID-19 Vaccine Research & Development in the Department of Surgery, Division of Surgical Sciences at Duke University Medical Center. His major research interests are viral immunology and HIV and COVID-19 vaccine development, with a special emphasis on neutralizing antibodies.

Multiple aspects of HIV-1 neutralizing antibodies are studied in his laboratory, including mechanisms of neutralization and escape, epitope diversity among the different genetic subtypes and geographic distributions of the virus, neutralizing epitopes, requirements to elicit protective neutralizing antibodies by vaccination, optimal combinations of neutralizing antibodies for immunoprophylaxis, and novel vaccine designs for HIV-1. Dr. Montefiori also directs large vaccine immune monitoring programs funded by the NIH and the Bill & Melinda Gates Foundation that operate in compliance with Good Clinical Laboratory Practices and has served as a national and international resource for standardized assessments of neutralizing antibody responses in preclinical and clinical trials of candidate HIV vaccines since 1988.

At the onset of the COVID-19 pandemic he turned his attention to SARS-CoV-2, with a special interest in emerging variants and how they might impact transmission, vaccines and immunotherapeutics. His rapid response to emerging SARS-CoV-2 variants of concern provided some of the earliest evidence of the potential risk the variants pose to vaccines. In May 2020, his laboratory was recruited by the US Government to lead the national neutralizing antibody laboratory program for COVID-19 vaccines.

His laboratory utilizes FDA approved validated assay criteria to facilitate regulatory approvals of COVID-19 vaccines. He has published over 750 original research papers that have helped shape the scientific rationale for antibody-based vaccines.