About

S. Munir Alam is a Professor in Medicine and a Professor of Pathology at Duke University. He is a member of the Duke Human Vaccine Institute. His professional roles are based at Duke's Department of Medicine, with a research focus that includes vaccine development and infectious diseases. His work involves contributions to the understanding of immune responses and vaccine strategies, supporting Duke's mission in advancing medical research and education.

Research topics

• Immunology
• Biology
• Virology
• Medicine
• Neuroscience
• Genetics
• Anatomy
• Computational biology
• Molecular biology
• Cell biology

Selected publications

• An engineered immunogen activates diverse HIV broadly neutralizing antibody precursors and promotes acquisition of improbable mutations

  Science Translational Medicine · 2025-01-08 · 5 citations

  article

  Elicitation of HIV broadly neutralizing antibodies (bnAbs) by vaccination first requires the activation of diverse precursors, followed by successive boosts that guide these responses to enhanced breadth through the acquisition of somatic mutations. Because HIV bnAbs contain mutations in their B cell receptors (BCRs) that are rarely generated during conventional B cell maturation, HIV vaccine immunogens must robustly engage and expand B cells with BCRs that contain these improbable mutations. Here, we engineered an immunogen that activates diverse precursors of an HIV V3-glycan bnAb and promotes their acquisition of a functionally critical improbable mutation. This immunogen was validated biochemically, structurally, and in three different humanized immunoglobulin mouse models that were designed to test HIV immunogens. These results provide a blueprint for rationally designing priming immunogens that explicitly target the elicitation of antibodies with functional yet improbable mutations.

  PublisherDOI

• Studying Gαi/o-Coupled Receptor Mediated Sensitization of Adenylyl Cyclases in SH-SY5Y Neuroblastoma Cells Using Fluorescent cAMP Sensors and Live-Cell Imaging (Abstract ID: 165805)

  Journal of Pharmacology and Experimental Therapeutics · 2025-03-01

  article1st authorCorresponding
  PublisherDOI

• Cryptic-site-specific antibodies to the SARS-CoV-2 receptor binding domain can retain functional binding affinity to spike variants

  UNC Libraries · 2025-01-08

  articleOpen access

  IMPORTANCE: Multiple SARS-CoV-2 variants of concern have emerged and caused a significant number of infections and deaths worldwide. These variants of concern contain mutations that might significantly affect antigen-targeting by antibodies. It is therefore important to further understand how antibody binding and neutralization are affected by the mutations in SARS-CoV-2 variants. We highlighted how antibody epitope specificity can influence antibody binding to SARS-CoV-2 spike protein variants and neutralization of SARS-CoV-2 variants. We showed that weakened spike binding and neutralization of Beta (B.1.351) and Omicron (BA.1) variants compared to wildtype are not universal among the panel of antibodies and identified antibodies of a specific binding footprint exhibiting consistent enhancement of spike binding and retained neutralization to Beta variant. These data and analysis can inform how antigen-targeting by antibodies might evolve during a pandemic and prepare for potential future sarbecovirus outbreaks.

  PublisherDOI

• Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans

  Cell · 2025-11-01

  articleOpen access
  PublisherDOI

• TitrationAnalysis: a tool for high throughput binding kinetics data analysis for multiple label-free platforms

  Gates Open Research · 2024-06-28 · 1 citations

  preprintOpen accessCorresponding

  <ns4:p> Label-free techniques including Surface Plasmon Resonance (SPR) and Biolayer Interferometry (BLI) are biophysical tools widely used to collect binding kinetics data of bimolecular interactions. To efficiently analyze SPR and BLI binding kinetics data, we have built a new high throughput analysis tool named the <ns4:italic>TitrationAnalysis</ns4:italic> . It can be used as a package in the Mathematica scripting environment and ultilize the non-linear curve-fitting module of Mathematica for its core function. This tool can fit the binding time course data and estimate association and dissociation rate constants ( <ns4:italic>ka</ns4:italic> and <ns4:italic>kd</ns4:italic> respectively) for determining apparent dissociation constant ( <ns4:italic>KD</ns4:italic> ) values. The high throughput fitting process is automatic, requires minimal knowledge on Mathematica scripting and can be applied to data from multiple label-free platforms. We demonstrate that the <ns4:italic>TitrationAnalysis</ns4:italic> is optimal to analyze antibody-antigen binding data acquired on Biacore T200 (SPR), Carterra LSA (SPR imaging) and ForteBio Octet Red384 (BLI) platforms. The <ns4:italic>ka</ns4:italic> , <ns4:italic>kd</ns4:italic> and <ns4:italic>KD</ns4:italic> values derived using <ns4:italic>TitrationAnalysis</ns4:italic> very closely matched the results from the commercial analysis software provided specifically for these instruments. Additionally, the <ns4:italic>TitrationAnalysis</ns4:italic> tool generates user-directed customizable results output that can be readily used in downstream Data Quality Control associated with Good Clinical Laboratory Practice operations. With the versatility in source of data input source and options of analysis result output, the <ns4:italic>TitrationAnalysis</ns4:italic> high throughput analysis tool offers investigators a powerful alternative in biomolecular interaction characterization. </ns4:p>

  PublisherOA PDFDOI

• Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans

  Cell · 2024-05-17 · 47 citations

  articleOpen accessCorresponding

  A critical roadblock to HIV vaccine development is the inability to induce B cell lineages of broadly neutralizing antibodies (bnAbs) in humans. In people living with HIV-1, bnAbs take years to develop. The HVTN 133 clinical trial studied a peptide/liposome immunogen targeting B cell lineages of HIV-1 envelope (Env) membrane-proximal external region (MPER) bnAbs (NCT03934541). Here, we report MPER peptide-liposome induction of polyclonal HIV-1 B cell lineages of mature bnAbs and their precursors, the most potent of which neutralized 15% of global tier 2 HIV-1 strains and 35% of clade B strains with lineage initiation after the second immunization. Neutralization was enhanced by vaccine selection of improbable mutations that increased antibody binding to gp41 and lipids. This study demonstrates proof of concept for rapid vaccine induction of human B cell lineages with heterologous neutralizing activity and selection of antibody improbable mutations and outlines a path for successful HIV-1 vaccine development.

  PublisherOA PDFDOI

• Mutation-guided vaccine design: A process for developing boosting immunogens for HIV broadly neutralizing antibody induction

  Cell Host & Microbe · 2024-04-25 · 28 citations

  article
  PublisherDOI

• Dynamics and Activation of Membrane-Bound B Cell Receptor Assembly

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-07-13 · 1 citations

  preprintOpen access

  B-cell receptor complexes (BCR) are expressed on the surface of a B-cell and are critical in antigen recognition and modulating the adaptive immune response. Even though the relevance of antibodies has been known for almost a hundred years, the antigen-dependent activation mechanism of B-cells has remained elusive. Several models have been proposed for BCR activation, including cross-linking, conformation-induced oligomerization, and dissociation activation models. Recently, the first cryo-EM structures of the human B-cell antigen receptor of the IgM and IgG isotypes were published that validated the asymmetric organization of the BCR complex. Here, we have carried out extensive molecular dynamics simulations to probe the conformational changes upon antigen binding and the influence of the membrane lipids. We identified two critical dynamical events that could be associated with antigen-dependent activation of BCR. First, antigen binding caused increased flexibility in regions distal to the antigen binding site. Second, antigen binding altered the rearrangement of IgM transmembrane helices, including the relative interaction of Igα/Igβ that mediates intracellular signaling. Furthermore, these transmembrane rearrangements led to changes in localized lipid composition.

  PublisherOA PDFDOI

• An HIV-1 gp41 peptide-liposome vaccine elicits neutralizing epitope-targeted antibody responses in healthy individuals

  medRxiv · 2024-03-18 · 7 citations

  preprintOpen access

  Broadly neutralizing antibodies (bnAbs) that target the HIV gp41 membrane-proximal external region (MPER) have some of the highest neutralization breadth. An MPER peptide-liposome vaccine has been found to expand MPER bnAb precursors in monkeys. The HVTN133 phase 1 clinical trial (NCT03934541) studied the MPER peptide-liposome immunogen in 24 HIV-1 seronegative individuals. Participants were randomized in a dose-escalation design to either 500 mcg or 2000 mcg of the MPER-peptide liposome or placebo. Four intramuscular injections were planned at months 0, 2, 6, and 12. The trial was stopped prematurely due to an anaphylaxis reaction in one participant attributed to vaccine-associated polyethylene glycol. The immunogen induced MPER-specific serum antibodies and CD4+ T-cell responses in 95% and 85% of vaccinees, respectively, and 35% of vaccine recipients had circulating IgG+ memory B cells with an MPER-bnAb binding phenotype. Affinity purification of plasma MPER-specific IgG demonstrated tier 2 HIV-1 neutralizing activity in two of five participants after 3 immunizations and tier 2 HIV-1 neutralizing B cell clonal lineages were isolated from MPER-reactive B cells. These results demonstrate that the HIV gp41 MPER region is a promising target for induction of heterologous neutralizing antibodies by a candidate HIV vaccine. Trial Registration: http://www.clinicaltrials.gov/ Identifier: NCT03934541.

  PublisherOA PDFDOI

• Vaccine induction of CD4-mimicking HIV-1 broadly neutralizing antibody precursors in macaques

  Cell · 2024-01-01 · 55 citations

  articleOpen access
  PublisherOA PDFDOI

Recent grants

• NIH Grant U19AI067854

  NIH · $294.0M · 2013

Frequent coauthors

• Barton F. Haynes

  Duke University

  172 shared

• David C. Montefiori

  Duke University

  132 shared

• Hua‐Xin Liao

  104 shared

• Georgia D. Tomaras

  Duke University

  101 shared

• M. Anthony Moody

  Duke University

  96 shared

• Kevin Wiehe

  Duke University

  87 shared

• Kevin O. Saunders

  Duke University

  83 shared

• Guido Ferrari

  Duke Medical Center

  72 shared