Scholars@Duke
Andrew Neil Macintyre

Andrew Neil Macintyre

Associate Professor in Medicine
Medicine, Duke Human Vaccine Institute
a.n.macintyre@duke.edu
Box 103020, Rm 1033 GHRB, 909 S. LaSalle St., Durham, NC 27710

Selected Publications

Spatiotemporal Control of Immune Responses with Nucleic Acid Cocktail Vaccine

Journal Article Advanced Therapeutics · November 1, 2024 Nucleic acid vaccines play important roles in the prevention and treatment of diseases. However, limited immunogenicity remains a major obstacle for DNA vaccine applications in the clinic. To address the issue, the present study investigates a cocktail app ... Full text Cite

Development and Validation of Multiplex Assays for Mouse and Human IgG and IgA to Neisseria gonorrhoeae Antigens.

Journal Article J Infect Dis · October 16, 2024 There is an urgent need for vaccines against Neisseria gonorrhoeae, the causative agent of gonorrhea. Vaccination with an outer membrane vesicle-based Neisseria meningitidis vaccine provides some protection from N. gonorrhoeae; however, the mechanisms unde ... Full text Link to item Cite

Improved influenza vaccine responses after expression of multiple viral glycoproteins from a single mRNA.

Journal Article Nat Commun · October 8, 2024 Influenza viruses cause substantial morbidity and mortality every year despite seasonal vaccination. mRNA-based vaccines have the potential to elicit more protective immune responses, but for maximal breadth and durability, it is desirable to deliver both ... Full text Link to item Cite

Sources of variability in Luminex bead-based cytokine assays: Evidence from twelve years of multi-site proficiency testing.

Journal Article J Immunol Methods · August 2024 Bead array assays, such as those sold by Luminex, BD Biosciences, Sartorius, Abcam and other companies, are a well-established platform for multiplexed quantification of cytokines and other biomarkers in both clinical and discovery research environments. I ... Full text Link to item Cite

Comprehensive Flow Cytometric, Immunohistologic, and Molecular Assessment of Thymus Function in Rhesus Macaques.

Journal Article Immunohorizons · July 1, 2024 The critical importance of the thymus for generating new naive T cells that protect against novel infections and are tolerant to self-antigens has led to a recent revival of interest in monitoring thymic function in species other than humans and mice. Nonh ... Full text Link to item Cite

Vaccination with antigenically complex hemagglutinin mixtures confers broad protection from influenza disease.

Journal Article Sci Transl Med · May 2024 Current seasonal influenza virus vaccines induce responses primarily against immunodominant but highly plastic epitopes in the globular head of the hemagglutinin (HA) glycoprotein. Because of viral antigenic drift at these sites, vaccines need to be update ... Full text Link to item Cite

A Narrative Review on Spontaneous Clearance of Urogenital Chlamydia trachomatis: Host, Microbiome, and Pathogen-Related Factors.

Journal Article Sex Transm Dis · February 1, 2024 Chlamydia trachomatis (CT) is the most commonly reported sexually transmitted infection in the United States. Untreated urogenital infection in women can result in adverse sequelae such as pelvic inflammatory disease and infertility. Despite national scree ... Full text Link to item Cite

The TLR2/TLR6 ligand FSL-1 mitigates radiation-induced hematopoietic injury in mice and nonhuman primates.

Journal Article Proc Natl Acad Sci U S A · December 12, 2023 Thrombocytopenia, hemorrhage, anemia, and infection are life-threatening issues following accidental or intentional radiation exposure. Since few therapeutics are available, safe and efficacious small molecules to mitigate radiation-induced injury need to ... Full text Link to item Cite

Transient inhibition of lysosomal functions potentiates nucleic acid vaccines.

Journal Article Proc Natl Acad Sci U S A · October 31, 2023 Nucleic acid vaccines have shown promising results in the clinic against infectious diseases and cancers. To robustly improve the vaccine efficacy and safety, we developed an approach to increase the intracellular stability of nucleic acids by transiently ... Full text Link to item Cite

Development and validation of an automated assay for anti-drug-antibodies in rat serum.

Journal Article SLAS Technol · October 2023 The potential immunogenicity of therapeutic human and humanized monoclonal antibodies (mAb) is a significant concern, and so preclinical testing of therapeutic mAbs routinely includes assessment of anti-drug antibody (ADA) induction. Here, we report the de ... Full text Link to item Cite

Neonatal SHIV infection in rhesus macaques elicited heterologous HIV-1-neutralizing antibodies.

Journal Article Cell Rep · March 28, 2023 Infants and children infected with human immunodeficiency virus (HIV)-1 have been shown to develop neutralizing antibodies (nAbs) against heterologous HIV-1 strains, characteristic of broadly nAbs (bnAbs). Thus, having a neonatal model for the induction of ... Full text Link to item Cite

Long-Term Immunological Consequences of Radiation Exposure in a Diverse Cohort of Rhesus Macaques.

Journal Article Int J Radiat Oncol Biol Phys · March 15, 2023 PURPOSE: The aim of this study was to develop an improved understanding of the delayed immunologic effects of acute total body irradiation (TBI) using a diverse cohort of nonhuman primates as a model for an irradiated human population. METHODS AND MATERIAL ... Full text Link to item Cite

Meningococcal Detoxified Outer Membrane Vesicle Vaccines Enhance Gonococcal Clearance in a Murine Infection Model.

Journal Article J Infect Dis · February 15, 2022 BACKGROUND: Despite decades of research efforts, development of a gonorrhea vaccine has remained elusive. Epidemiological studies suggest that detoxified outer membrane vesicle (dOMV) vaccines from Neisseria meningitidis (Nm) may protect against infection ... Full text Link to item Cite

Targeting Glycolysis in Alloreactive T Cells to Prevent Acute Graft-Versus-Host Disease While Preserving Graft-Versus-Leukemia Effect.

Journal Article Front Immunol · 2022 Alloreactive donor T cells undergo extensive metabolic reprogramming to become activated and induce graft-versus-host disease (GVHD) upon alloantigen encounter. It is generally thought that glycolysis, which promotes T cell growth and clonal expansion, is ... Full text Link to item Cite

Vaginal cytokine profile and microbiota before and after lubricant use compared with condomless vaginal sex: a preliminary observational study.

Journal Article BMC Infect Dis · September 18, 2021 BACKGROUND: Limited data suggest that personal lubricants may damage the vaginal mucosal epithelium, alter the vaginal microbiota, and increase inflammation. We compared vaginal cytokine profiles and microbiota before and after vaginal lubricant use and co ... Full text Link to item Cite

Preclinical Testing of Vaccines and Therapeutics for Gonorrhea in Female Mouse Models of Lower and Upper Reproductive Tract Infection.

Journal Article J Infect Dis · August 16, 2021 Murine models of Neisseria gonorrhoeae lower reproductive tract infection are valuable systems for studying N. gonorrhoeae adaptation to the female host and immune responses to infection. These models have also accelerated preclinical testing of candidate ... Full text Link to item Cite

In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies.

Journal Article Cell · August 5, 2021 SARS-CoV-2-neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) or the N-terminal domain (NTD) of SA ... Full text Open Access Link to item Cite

Bacteremia in solid organ transplant recipients as compared to immunocompetent patients: Acute phase cytokines and outcomes in a prospective, matched cohort study.

Journal Article Am J Transplant · June 2021 We undertook a prospective, matched cohort study of patients with Staphylococcus aureus bacteremia (SAB) and gram-negative bacteremia (GNB) to compare the characteristics, outcomes, and chemokine and cytokine response in transplant recipients to immunocomp ... Full text Open Access Link to item Cite

T cell-depleted cultured pediatric thymus tissue as a model for some aspects of human age-related thymus involution.

Journal Article Geroscience · June 2021 Human age-related thymus involution is characterized by loss of developing thymocytes and the thymic epithelial network that supports them, with replacement by adipose tissue. The mechanisms that drive these changes are difficult to study in vivo due to co ... Full text Open Access Link to item Cite

Data and Code from: T Cell-Depleted Cultured Pediatric Thymus Tissue as a Model for Some Aspects of Human Age-Related Thymus Involution

Dataset · January 4, 2021 Human age-related thymus involution is characterized by loss of developing thymocytes and the thymic epithelial network that supports them, with replacement by adipose tissue. The mechanisms that drive these changes are difficult to study in vivo due to co ... Full text Cite

Long-Term Recovery of the Adaptive Immune System in Rhesus Macaques After Total Body Irradiation.

Journal Article Adv Radiat Oncol · 2021 PURPOSE: Ionizing radiation causes acute damage to hematopoietic and immune cells, but the long-term immunologic consequences of irradiation are poorly understood. We therefore performed a prospective study of the delayed immune effects of radiation using ... Full text Link to item Cite

Altering the Immunogenicity of Hemagglutinin Immunogens by Hyperglycosylation and Disulfide Stabilization.

Journal Article Front Immunol · 2021 Influenza virus alters glycosylation patterns on its surface exposed glycoproteins to evade host adaptive immune responses. The viral hemagglutinin (HA), in particular the H3 subtype, has increased its overall surface glycosylation since its introduction i ... Full text Link to item Cite

Cervicovaginal Microbiota Predicts Neisseria gonorrhoeae Clinical Presentation.

Journal Article Front Microbiol · 2021 Neisseria gonorrhoeae infection of the female lower genital tract can present with a spectrum of phenotypes ranging from asymptomatic carriage to symptomatic cervical inflammation, or cervicitis. The factors that contribute to the development of asymptomat ... Full text Link to item Cite

The serogroup B meningococcal outer membrane vesicle-based vaccine 4CMenB induces cross-species protection against Neisseria gonorrhoeae.

Journal Article PLoS Pathog · December 2020 There is a pressing need for a gonorrhea vaccine due to the high disease burden associated with gonococcal infections globally and the rapid evolution of antibiotic resistance in Neisseria gonorrhoeae (Ng). Current gonorrhea vaccine research is in the stag ... Full text Link to item Cite

Multi-omics analyses of radiation survivors identify radioprotective microbes and metabolites.

Journal Article Science · October 30, 2020 Ionizing radiation causes acute radiation syndrome, which leads to hematopoietic, gastrointestinal, and cerebrovascular injuries. We investigated a population of mice that recovered from high-dose radiation to live normal life spans. These "elite-survivors ... Full text Link to item Cite

Monocyte Polarization is Altered by Total-Body Irradiation in Male Rhesus Macaques: Implications for Delayed Effects of Acute Radiation Exposure.

Journal Article Radiat Res · August 2019 Radiation-induced fibrosis (RIF) is a common delayed effect of acute ionizing radiation exposure (DEARE) affecting diverse tissues including the heart, lungs, liver and skin, leading to reduced tissue function and increased morbidity. Monocytes, which may ... Full text Link to item Cite

Antigen receptor control of methionine metabolism in T cells.

Journal Article Elife · March 27, 2019 Immune activated T lymphocytes modulate the activity of key metabolic pathways to support the transcriptional reprograming and reshaping of cell proteomes that permits effector T cell differentiation. The present study uses high resolution mass spectrometr ... Full text Link to item Cite

Acetalated Dextran Microparticles for Codelivery of STING and TLR7/8 Agonists.

Journal Article Mol Pharm · November 5, 2018 Vaccines are the most effective tool for preventing infectious diseases; however, subunit vaccines, considered the safest type, suffer from poor immunogenicity and require adjuvants to create a strong and sustained immune response. As adjuvants, pathogen-a ... Full text Link to item Cite

AMPK Is Essential to Balance Glycolysis and Mitochondrial Metabolism to Control T-ALL Cell Stress and Survival.

Journal Article Cell Metab · April 12, 2016 T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy associated with Notch pathway mutations. While both normal activated and leukemic T cells can utilize aerobic glycolysis to support proliferation, it is unclear to what extent these ce ... Full text Link to item Cite

Phosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T Cell Responses.

Journal Article Cell · September 10, 2015 Activated T cells engage aerobic glycolysis and anabolic metabolism for growth, proliferation, and effector functions. We propose that a glucose-poor tumor microenvironment limits aerobic glycolysis in tumor-infiltrating T cells, which suppresses tumoricid ... Full text Link to item Cite

Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation.

Journal Article J Clin Invest · January 2015 Activation of CD4+ T cells results in rapid proliferation and differentiation into effector and regulatory subsets. CD4+ effector T cell (Teff) (Th1 and Th17) and Treg subsets are metabolically distinct, yet the specific metabolic differences that modify T ... Full text Open Access Link to item Cite

Glucose transporter 1-mediated glucose uptake is limiting for B-cell acute lymphoblastic leukemia anabolic metabolism and resistance to apoptosis.

Journal Article Cell Death Dis · October 16, 2014 The metabolic profiles of cancer cells have long been acknowledged to be altered and to provide new therapeutic opportunities. In particular, a wide range of both solid and liquid tumors use aerobic glycolysis to supply energy and support cell growth. This ... Full text Link to item Cite

The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function.

Journal Article Cell Metab · July 1, 2014 CD4 T cell activation leads to proliferation and differentiation into effector (Teff) or regulatory (Treg) cells that mediate or control immunity. While each subset prefers distinct glycolytic or oxidative metabolic programs in vitro, requirements and mech ... Full text Link to item Cite

Metabolic reprogramming of macrophages: glucose transporter 1 (GLUT1)-mediated glucose metabolism drives a proinflammatory phenotype.

Journal Article J Biol Chem · March 14, 2014 Glucose is a critical component in the proinflammatory response of macrophages (MΦs). However, the contribution of glucose transporters (GLUTs) and the mechanisms regulating subsequent glucose metabolism in the inflammatory response are not well understood ... Full text Link to item Cite

Metabolic reprogramming towards aerobic glycolysis correlates with greater proliferative ability and resistance to metabolic inhibition in CD8 versus CD4 T cells.

Journal Article PLoS One · 2014 T lymphocytes (T cells) undergo metabolic reprogramming after activation to provide energy and biosynthetic materials for growth, proliferation and differentiation. Distinct T cell subsets, however, adopt metabolic programs specific to support their needs. ... Full text Link to item Cite

Engineering a BCR-ABL-activated caspase for the selective elimination of leukemic cells.

Journal Article Proc Natl Acad Sci U S A · February 5, 2013 Increased understanding of the precise molecular mechanisms involved in cell survival and cell death signaling pathways offers the promise of harnessing these molecules to eliminate cancer cells without damaging normal cells. Tyrosine kinase oncoproteins p ... Full text Open Access Link to item Cite

Activated lymphocytes as a metabolic model for carcinogenesis.

Journal Article Cancer Metab · January 23, 2013 Metabolic reprogramming is a key event in tumorigenesis to support cell growth, and cancer cells frequently become both highly glycolytic and glutamine dependent. Similarly, T lymphocytes (T cells) modify their metabolism after activation by foreign antige ... Full text Link to item Cite

Akt-dependent glucose metabolism promotes Mcl-1 synthesis to maintain cell survival and resistance to Bcl-2 inhibition.

Journal Article Cancer Res · August 1, 2011 Most cancer cells utilize aerobic glycolysis, and activation of the phosphoinositide 3-kinase/Akt/mTOR pathway can promote this metabolic program to render cells glucose dependent. Although manipulation of glucose metabolism may provide a means to specific ... Full text Link to item Cite

PKM2 and the tricky balance of growth and energy in cancer.

Journal Article Mol Cell · June 24, 2011 In this issue of Molecular Cell, Lv et al. (2011) identify a novel feedback mechanism in which increased glycolysis induces the acetylation and chaperone-mediated autophagic degradation of the glycolytic regulator PKM2, revealing a novel metabolic feedback ... Full text Link to item Cite

Autophagy is essential to suppress cell stress and to allow BCR-Abl-mediated leukemogenesis.

Journal Article Oncogene · April 21, 2011 Hematopoietic cells normally require cell extrinsic signals to maintain metabolism and survival. In contrast, cancer cells can express constitutively active oncogenic kinases such as BCR-Abl that promote these processes independent of extrinsic growth fact ... Full text Link to item Cite

Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets.

Journal Article J Immunol · March 15, 2011 Stimulated CD4(+) T lymphocytes can differentiate into effector T cell (Teff) or inducible regulatory T cell (Treg) subsets with specific immunological roles. We show that Teff and Treg require distinct metabolic programs to support these functions. Th1, T ... Full text Open Access Link to item Cite

Protein kinase B controls transcriptional programs that direct cytotoxic T cell fate but is dispensable for T cell metabolism.

Journal Article Immunity · February 25, 2011 In cytotoxic T cells (CTL), Akt, also known as protein kinase B, is activated by the T cell antigen receptor (TCR) and the cytokine interleukin 2 (IL-2). Akt can control cell metabolism in many cell types but whether this role is important for CTL function ... Full text Link to item Cite

LKB1 is essential for the proliferation of T-cell progenitors and mature peripheral T cells.

Journal Article Eur J Immunol · January 2010 The serine/threonine kinase LKB1 has a conserved role in Drosophila and nematodes to co-ordinate cell metabolism. During T lymphocyte development in the thymus, progenitors need to synchronize increased metabolism with the onset of proliferation and differ ... Full text Link to item Cite

Discovery and characterization of human antibody inhibitors of pregnancy-associated plasma protein-A.

Journal Article Biol Chem · May 2007 Pregnancy-associated plasma protein-A (PAPP-A) is a metalloprotease that cleaves insulin-like growth factor-binding proteins (IGFBPs) to release bioactive levels of free insulin-like growth factor. Specific and potent inhibitors of PAPP-A may further eluci ... Full text Link to item Cite

Compartmentalization of cAMP-dependent signaling by phosphodiesterase-4D is involved in the regulation of vasopressin-mediated water reabsorption in renal principal cells.

Journal Article J Am Soc Nephrol · January 2007 The cAMP/protein kinase A (PKA)-dependent insertion of water channel aquaporin-2 (AQP2)-bearing vesicles into the plasma membrane in renal collecting duct principal cells (AQP2 shuttle) constitutes the molecular basis of arginine vasopressin (AVP)-regulate ... Full text Link to item Cite