Scholars@Duke
S. Munir Alam

S. Munir Alam

Professor in Medicine
Medicine, Duke Human Vaccine Institute
alam0004@mc.duke.edu
BOX103020, Durham, NC 27710
2 Genome Ct, MSRB II - Room 4004, Durham, NC 27710

Featured Works

HIV-1 antibodies and vaccine antigen selectively interact with lipid domains.

Journal article Biochim Biophys Acta · October 2014 Featured Publication The rare, broadly neutralizing antibodies, 4E10 and 2F5, that target the HIV-1 membrane proximal external region also associate with HIV-1 membrane lipids as part of a required first-step in HIV-1 neutralization. HIV-1 virions have high concentration of ch ... Full text Link to item Cite

HIV-1 envelope gp41 antibodies can originate from terminal ileum B cells that share cross-reactivity with commensal bacteria.

Journal article Cell Host Microbe · August 13, 2014 Featured Publication Monoclonal antibodies derived from blood plasma cells of acute HIV-1-infected individuals are predominantly targeted to the HIV Env gp41 and cross-reactive with commensal bacteria. To understand this phenomenon, we examined anti-HIV responses in ileum B ce ... Full text Open Access Link to item Cite

Vaccine-induced HIV-1 envelope gp120 constant region 1-specific antibodies expose a CD4-inducible epitope and block the interaction of HIV-1 gp140 with galactosylceramide.

Journal article J Virol · August 2014 Featured Publication UNLABELLED: Mucosal epithelial cell surface galactosylceramide (Galcer) has been postulated to be a receptor for HIV-1 envelope (Env) interactions with mucosal epithelial cells. Disruption of the HIV-1 Env interaction with such alternate receptors could be ... Full text Link to item Cite

HIV-1 vaccine-induced C1 and V2 Env-specific antibodies synergize for increased antiviral activities.

Journal article J Virol · July 2014 Featured Publication The RV144 ALVAC/AIDSVax HIV-1 vaccine clinical trial showed an estimated vaccine efficacy of 31.2%. Viral genetic analysis identified a vaccine-induced site of immune pressure in the HIV-1 envelope (Env) variable region 2 (V2) focused on residue 169, which ... Full text Link to item Cite

Enhanced antibody responses to an HIV-1 membrane-proximal external region antigen in mice reconstituted with cultured lymphocytes.

Journal article J Immunol · April 1, 2014 Featured Publication We have shown that the protective HIV-1 Ab, 2F5, avidly reacts with a conserved mammalian self-Ag, kynureninase, and that the development of B cells specific for the 2F5 epitope is constrained by immunological tolerance. These observations suggest that the ... Full text Link to item Cite

TCR affinity associated with functional differences between dominant and subdominant SIV epitope-specific CD8+ T cells in Mamu-A*01+ rhesus monkeys.

Journal article PLoS Pathog · April 2014 Featured Publication Many of the factors that contribute to CD8+ T cell immunodominance hierarchies during viral infection are known. However, the functional differences that exist between dominant and subdominant epitope-specific CD8+ T cells remain poorly understood. In this ... Full text Link to item Cite

Vaccine-induced Env V1-V2 IgG3 correlates with lower HIV-1 infection risk and declines soon after vaccination.

Journal article Sci Transl Med · March 19, 2014 Featured Publication HIV-1-specific immunoglobulin G (IgG) subclass antibodies bind to distinct cellular Fc receptors. Antibodies of the same epitope specificity but of a different subclass therefore can have different antibody effector functions. The study of IgG subclass pro ... Full text Link to item Cite

Toll-like receptor 7/8 (TLR7/8) and TLR9 agonists cooperate to enhance HIV-1 envelope antibody responses in rhesus macaques.

Journal article J Virol · March 2014 Featured Publication UNLABELLED: The development of a vaccine that can induce high titers of functional antibodies against HIV-1 remains a high priority. We have developed an adjuvant based on an oil-in-water emulsion that incorporates Toll-like receptor (TLR) ligands to test ... Full text Link to item Cite

Modulation of nonneutralizing HIV-1 gp41 responses by an MHC-restricted TH epitope overlapping those of membrane proximal external region broadly neutralizing antibodies.

Journal article J Immunol · February 15, 2014 Featured Publication A goal of HIV-1 vaccine development is to elicit broadly neutralizing Abs (BnAbs), but current immunization strategies fail to induce BnAbs, and for unknown reasons, often induce nonneutralizing Abs instead. To explore potential host genetic contributions ... Full text Link to item Cite

Surface plasmon resonance measurements of plasma antibody avidity during primary and secondary responses to anthrax protective antigen.

Journal article J Immunol Methods · February 2014 Featured Publication Establishment of humoral immunity against pathogens is dependent on events that occur in the germinal center and the subsequent induction of high-affinity neutralizing antibodies. Quantitative assays that allow monitoring of affinity maturation and duratio ... Full text Link to item Cite

Structure of an HIV-1-neutralizing antibody target, the lipid-bound gp41 envelope membrane proximal region trimer.

Journal article Proc Natl Acad Sci U S A · January 28, 2014 Featured Publication The membrane proximal external region (MPER) of HIV-1 glycoprotein (gp) 41 is involved in viral-host cell membrane fusion. It contains short amino acid sequences that are binding sites for the HIV-1 broadly neutralizing antibodies 2F5, 4E10, and 10E8, maki ... Full text Link to item Cite

Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV.

Journal article Nature · January 23, 2014 Featured Publication A major challenge for the development of a highly effective AIDS vaccine is the identification of mechanisms of protective immunity. To address this question, we used a nonhuman primate challenge model with simian immunodeficiency virus (SIV). We show that ... Full text Open Access Link to item Cite

Estimating the probability of polyreactive antibodies 4E10 and 2F5 disabling a gp41 trimer after T cell-HIV adhesion.

Journal article PLoS Comput Biol · January 2014 Featured Publication A few broadly neutralizing antibodies, isolated from HIV-1 infected individuals, recognize epitopes in the membrane proximal external region (MPER) of gp41 that are transiently exposed during viral entry. The best characterized, 4E10 and 2F5, are polyreact ... Full text Link to item Cite

Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV

Journal article Nature · January 1, 2014 Featured Publication A major challenge for the development of a highly effective AIDS vaccine is the identification of mechanisms of protective immunity. To address this question, we used a nonhuman primate challenge model with simian immunodeficiency virus (SIV). We show that ... Full text Open Access Cite

Estimating the Probability of Polyreactive Antibodies 4E10 and 2F5 Disabling a gp41 Trimer after T Cell-HIV Adhesion

Journal article Plos Computational Biology · January 1, 2014 Featured Publication A few broadly neutralizing antibodies, isolated from HIV-1 infected individuals, recognize epitopes in the membrane proximal external region (MPER) of gp41 that are transiently exposed during viral entry. The best characterized, 4E10 and 2F5, are polyreact ... Full text Cite

Reconstructing a B-Cell Clonal Lineage. II. Mutation, Selection, and Affinity Maturation.

Journal article Front Immunol · 2014 Featured Publication Affinity maturation of the antibody response is a fundamental process in adaptive immunity during which B-cells activated by infection or vaccination undergo rapid proliferation accompanied by the acquisition of point mutations in their rearranged immunogl ... Full text Open Access Link to item Cite

Recognition of synthetic glycopeptides by HIV-1 broadly neutralizing antibodies and their unmutated ancestors.

Journal article Proc Natl Acad Sci U S A · November 5, 2013 Featured Publication Current HIV-1 vaccines elicit strain-specific neutralizing antibodies. Broadly neutralizing antibodies (BnAbs) are not induced by current vaccines, but are found in plasma in ∼20% of HIV-1-infected individuals after several years of infection. One strategy ... Full text Link to item Cite

Tenascin-C is an innate broad-spectrum, HIV-1-neutralizing protein in breast milk.

Journal article Proc Natl Acad Sci U S A · November 5, 2013 Featured Publication Achieving an AIDS-free generation will require elimination of postnatal transmission of HIV-1 while maintaining the nutritional and immunologic benefits of breastfeeding for infants in developing regions. Maternal/infant antiretroviral prophylaxis can redu ... Full text Open Access Link to item Cite

Intestinal Commensal Bacteria Shape the Pre-transmission Antibody Repertoire to HIV-1 Infection

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · November 1, 2013 Featured Publication Link to item Cite

Chemical synthesis of highly congested gp120 V1V2 N-glycopeptide antigens for potential HIV-1-directed vaccines.

Journal article J Am Chem Soc · September 4, 2013 Featured Publication Critical to the search for an effective HIV-1 vaccine is the development of immunogens capable of inducing broadly neutralizing antibodies (BnAbs). A key first step in this process is to design immunogens that can be recognized by known BnAbs. The monoclon ... Full text Link to item Cite

Induction of HIV-1 broad neutralizing antibodies in 2F5 knock-in mice: selection against membrane proximal external region-associated autoreactivity limits T-dependent responses.

Journal article J Immunol · September 1, 2013 Featured Publication A goal of HIV-1 vaccine development is to elicit broadly neutralizing Abs (BnAbs). Using a knock-in (KI) model of 2F5, a human HIV-1 gp41 membrane proximal external region (MPER)-specific BnAb, we previously demonstrated that a key obstacle to BnAb inducti ... Full text Link to item Cite

Infectious virion capture by HIV-1 gp120-specific IgG from RV144 vaccinees.

Journal article J Virol · July 2013 Featured Publication The detailed examination of the antibody repertoire from RV144 provides a unique template for understanding potentially protective antibody functions. Some potential immune correlates of protection were untested in the correlates analyses due to inherent a ... Full text Open Access Link to item Cite

Structural basis for diverse N-glycan recognition by HIV-1-neutralizing V1-V2-directed antibody PG16.

Journal article Nat Struct Mol Biol · July 2013 Featured Publication HIV-1 uses a diverse N-linked-glycan shield to evade recognition by antibody. Select human antibodies, such as the clonally related PG9 and PG16, recognize glycopeptide epitopes in the HIV-1 V1-V2 region and penetrate this shield, but their ability to acco ... Full text Link to item Cite

Vaccine-induced plasma IgA specific for the C1 region of the HIV-1 envelope blocks binding and effector function of IgG.

Journal article Proc Natl Acad Sci U S A · May 28, 2013 Featured Publication Analysis of correlates of risk of infection in the RV144 HIV-1 vaccine efficacy trial demonstrated that plasma IgG against the HIV-1 envelope (Env) variable region 1 and 2 inversely correlated with risk, whereas HIV-1 Env-specific plasma IgA responses dire ... Full text Link to item Cite

Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus.

Journal article Nature · April 25, 2013 Featured Publication Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals, and details of their generation could provide ... Full text Open Access Link to item Cite

Mining the antibodyome for HIV-1-neutralizing antibodies with next-generation sequencing and phylogenetic pairing of heavy/light chains.

Journal article Proc Natl Acad Sci U S A · April 16, 2013 Featured Publication Next-generation sequencing of antibody transcripts from HIV-1-infected individuals with broadly neutralizing antibodies could provide an efficient means for identifying somatic variants and characterizing their lineages. Here, we used 454 pyrosequencing an ... Full text Link to item Cite

Antigenicity and immunogenicity of transmitted/founder, consensus, and chronic envelope glycoproteins of human immunodeficiency virus type 1.

Journal article J Virol · April 2013 Featured Publication Human immunodeficiency virus type 1 (HIV-1) vaccine development requires selection of appropriate envelope (Env) immunogens. Twenty HIV-1 Env glycoproteins were examined for their ability to bind human anti-HIV-1 monoclonal antibodies (MAbs) and then used ... Full text Link to item Cite

Characterization of host-cell line specific glycosylation profiles of early transmitted/founder HIV-1 gp120 envelope proteins.

Journal article J Proteome Res · March 1, 2013 Featured Publication Glycosylation plays an essential role in regulating protein function by modulating biological, structural, and therapeutic properties. However, due to its inherent heterogeneity and diversity, the comprehensive analysis of protein glycosylation remains a c ... Full text Link to item Cite

Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies.

Journal article J Exp Med · February 11, 2013 Featured Publication Many human monoclonal antibodies that neutralize multiple clades of HIV-1 are polyreactive and bind avidly to mammalian autoantigens. Indeed, the generation of neutralizing antibodies to the 2F5 and 4E10 epitopes of HIV-1 gp41 in man may be proscribed by i ... Full text Open Access Link to item Cite

Antigenicity and immunogenicity of RV144 vaccine AIDSVAX clade E envelope immunogen is enhanced by a gp120 N-terminal deletion.

Journal article J Virol · February 2013 Featured Publication An immune correlates analysis of the RV144 HIV-1 vaccine trial revealed that antibody responses to the gp120 V1/V2 region correlated inversely with infection risk. The RV144 protein immunogens (A244-rp120 and MN-rgp120) were modified by an N-terminal 11-am ... Full text Link to item Cite

Antibodies with high avidity to the gp120 envelope protein in protection from simian immunodeficiency virus SIV(mac251) acquisition in an immunization regimen that mimics the RV-144 Thai trial.

Journal article J Virol · February 2013 Featured Publication The recombinant canarypox vector, ALVAC-HIV, together with human immunodeficiency virus (HIV) gp120 envelope glycoprotein, has protected 31.2% of Thai individuals from HIV acquisition in the RV144 HIV vaccine trial. This outcome was unexpected, given the l ... Full text Link to item Cite

Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2.

Journal article Immunity · January 24, 2013 Featured Publication The RV144 HIV-1 trial of the canary pox vector (ALVAC-HIV) plus the gp120 AIDSVAX B/E vaccine demonstrated an estimated efficacy of 31%, which correlated directly with antibodies to HIV-1 envelope variable regions 1 and 2 (V1-V2). Genetic analysis of trial ... Full text Link to item Cite

Postnatally-transmitted HIV-1 Envelope variants have similar neutralization-sensitivity and function to that of nontransmitted breast milk variants.

Journal article Retrovirology · January 10, 2013 Featured Publication BACKGROUND: Breastfeeding is a leading cause of infant HIV-1 infection in the developing world, yet only a minority of infants exposed to HIV-1 via breastfeeding become infected. As a genetic bottleneck severely restricts the number of postnatally-transmit ... Full text Open Access Link to item Cite

Broad and potent neutralization of HIV-1 by a gp41-specific human antibody.

Journal article Nature · November 15, 2012 Featured Publication Characterization of human monoclonal antibodies is providing considerable insight into mechanisms of broad HIV-1 neutralization. Here we report an HIV-1 gp41 membrane-proximal external region (MPER)-specific antibody, named 10E8, which neutralizes ∼98% of ... Full text Link to item Cite

HIV-1 antibodies from infection and vaccination: insights for guiding vaccine design.

Journal article Trends Microbiol · November 2012 Featured Publication Attempts to formulate a protective HIV-1 vaccine through classic vaccine design strategies have not been successful. Elicitation of HIV-1-specific broadly neutralizing antibodies (bnAbs) at high titers that are present before exposure might be required to ... Full text Link to item Cite

CD4 T follicular helper cell dynamics during SIV infection.

Journal article J Clin Invest · September 2012 Featured Publication CD4 T follicular helper (TFH) cells interact with and stimulate the generation of antigen-specific B cells. TFH cell interaction with B cells correlates with production of SIV-specific immunoglobulins. However, the fate of TFH cells and their participation ... Full text Link to item Cite

HIV-1 gp120 vaccine induces affinity maturation in both new and persistent antibody clonal lineages.

Journal article J Virol · July 2012 Featured Publication Most antibodies that broadly neutralize HIV-1 are highly somatically mutated in antibody clonal lineages that persist over time. Here, we describe the analysis of human antibodies induced during an HIV-1 vaccine trial (GSK PRO HIV-002) that used the clade ... Full text Link to item Cite

Immune-correlates analysis of an HIV-1 vaccine efficacy trial.

Journal article N Engl J Med · April 5, 2012 Featured Publication BACKGROUND: In the RV144 trial, the estimated efficacy of a vaccine regimen against human immunodeficiency virus type 1 (HIV-1) was 31.2%. We performed a case-control analysis to identify antibody and cellular immune correlates of infection risk. METHODS: ... Full text Link to item Cite

Screening the interactions between HIV-1 neutralizing antibodies and model lipid surfaces.

Journal article J Immunol Methods · February 28, 2012 Featured Publication Our work is motivated by the observation that rare, broadly neutralizing antibodies (NAbs), 4E10 and 2F5, associate with HIV-1 lipids as part of a required first step in neutralization before binding to membrane-proximal antigens. Subsequently, induction o ... Full text Link to item Cite

Isolation of HIV-1-neutralizing mucosal monoclonal antibodies from human colostrum.

Journal article PLoS One · 2012 Featured Publication BACKGROUND: Generation of potent anti-HIV antibody responses in mucosal compartments is a potential requirement of a transmission-blocking HIV vaccine. HIV-specific, functional antibody responses are present in breast milk, and these mucosal antibody respo ... Full text Open Access Link to item Cite