Derek Wilson Cain

Journal Article J Clin Invest · November 12, 2024 Human cytomegalovirus (HCMV) profoundly impacts host T and natural killer (NK) cells across the lifespan, yet how this common congenital infection modulates developing fetal immune cell compartments remains underexplored. Using cord blood from neonates wit ... Full text Link to item Cite

Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies.

Journal Article Nat Commun · November 3, 2024 Vaccine development targeting rapidly evolving pathogens such as HIV-1 requires induction of broadly neutralizing antibodies (bnAbs) with conserved paratopes and mutations, and in some cases, the same Ig-heavy chains. The current trial-and-error search for ... Full text Link to item Cite

Comparison of the immunogenicity of mRNA-encoded and protein HIV-1 Env-ferritin nanoparticle designs.

Journal Article J Virol · September 17, 2024 Nucleoside-modified mRNA technology has revolutionized vaccine development with the success of mRNA COVID-19 vaccines. We used modified mRNA technology for the design of envelopes (Env) to induce HIV-1 broadly neutralizing antibodies (bnAbs). However, unli ... Full text Link to item Cite

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

Journal Article Cell · June 6, 2024 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/liposom ... Full text Link to item Cite

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

Journal Article Cell Host Microbe · May 8, 2024 A major goal of HIV-1 vaccine development is the induction of broadly neutralizing antibodies (bnAbs). Although success has been achieved in initiating bnAb B cell lineages, design of boosting immunogens that select for bnAb B cell receptors with improbabl ... Full text Link to item Cite

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

Journal Article Cell · January 4, 2024 The CD4-binding site (CD4bs) is a conserved epitope on HIV-1 envelope (Env) that can be targeted by protective broadly neutralizing antibodies (bnAbs). HIV-1 vaccines have not elicited CD4bs bnAbs for many reasons, including the occlusion of CD4bs by glyca ... Full text Link to item Cite

Engineered immunogens to elicit antibodies against conserved coronavirus epitopes.

Journal Article Nat Commun · November 30, 2023 Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing residues 815 ... Full text Link to item Cite

Conjugation of HIV-1 envelope to hepatitis B surface antigen alters vaccine responses in rhesus macaques.

Journal Article NPJ Vaccines · November 24, 2023 An effective HIV-1 vaccine remains a critical unmet need for ending the AIDS epidemic. Vaccine trials conducted to date have suggested the need to increase the durability and functionality of vaccine-elicited antibodies to improve efficacy. We hypothesized ... Full text Open Access Link to item Cite

International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.

Journal Article Pharmacol Rev · November 2023 The NR superfamily comprises 48 transcription factors in humans that control a plethora of gene network programs involved in a wide range of physiologic processes. This review will summarize and discuss recent progress in NR biology and drug development 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

A Germline-Targeting Chimpanzee SIV Envelope Glycoprotein Elicits a New Class of V2-Apex Directed Cross-Neutralizing Antibodies.

Journal Article mBio · February 28, 2023 HIV-1 and its SIV precursors share a broadly neutralizing antibody (bNAb) epitope in variable loop 2 (V2) at the envelope glycoprotein (Env) trimer apex. Here, we tested the immunogenicity of germ line-targeting versions of a chimpanzee SIV (SIVcpz) Env in ... Full text Link to item Cite

Breadth of SARS-CoV-2 neutralization and protection induced by a nanoparticle vaccine.

Journal Article Nat Commun · October 23, 2022 Coronavirus vaccines that are highly effective against current and anticipated SARS-CoV-2 variants are needed to control COVID-19. We previously reported a receptor-binding domain (RBD)-sortase A-conjugated ferritin nanoparticle (scNP) vaccine that induced ... Full text Open Access Link to item Cite

Stabilized HIV-1 envelope immunization induces neutralizing antibodies to the CD4bs and protects macaques against mucosal infection.

Journal Article Sci Transl Med · September 7, 2022 A successful HIV-1 vaccine will require induction of a polyclonal neutralizing antibody (nAb) response, yet vaccine-mediated induction of such a response in primates remains a challenge. We found that a stabilized HIV-1 CH505 envelope (Env) trimer formulat ... Full text Open Access Link to item Cite

Mouse and human antibodies bind HLA-E-leader peptide complexes and enhance NK cell cytotoxicity.

Journal Article Commun Biol · March 28, 2022 The non-classical class Ib molecule human leukocyte antigen E (HLA-E) has limited polymorphism and can bind HLA class Ia leader peptides (VL9). HLA-E-VL9 complexes interact with the natural killer (NK) cell receptors NKG2A-C/CD94 and regulate NK cell-media ... Full text Link to item Cite

mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralize heterologous HIV-1 isolates in mice.

Journal Article Cell Rep · March 15, 2022 The success of nucleoside-modified mRNAs in lipid nanoparticles (mRNA-LNP) as COVID-19 vaccines heralded a new era of vaccine development. For HIV-1, multivalent envelope (Env) trimer protein nanoparticles are superior immunogens compared with trimers alon ... Full text Link to item Cite

Strategies for eliciting multiple lineages of broadly neutralizing antibodies to HIV by vaccination.

Journal Article Curr Opin Virol · December 2021 A prophylactic vaccine would be a powerful tool in the fight against HIV. Passive immunization of animals with broadly neutralizing antibodies (bnAbs) affords protection against viral challenge, and recent data from the Antibody Mediated Prevention clinica ... 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

HIV envelope antigen valency on peptide nanofibers modulates antibody magnitude and binding breadth.

Journal Article Sci Rep · July 14, 2021 A major challenge in developing an effective vaccine against HIV-1 is the genetic diversity of its viral envelope. Because of the broad range of sequences exhibited by HIV-1 strains, protective antibodies must be able to bind and neutralize a widely mutate ... Full text Link to item Cite

HIV mRNA Vaccines-Progress and Future Paths.

Journal Article Vaccines (Basel) · February 7, 2021 The SARS-CoV-2 pandemic introduced the world to a new type of vaccine based on mRNA encapsulated in lipid nanoparticles (LNPs). Instead of delivering antigenic proteins directly, an mRNA-based vaccine relies on the host's cells to manufacture protein immun ... Full text Link to item Cite

RAB11FIP5-Deficient Mice Exhibit Cytokine-Related Transcriptomic Signatures.

Journal Article Immunohorizons · November 10, 2020 Rab11 recycling endosomes are involved in immunological synaptic functions, but the roles of Rab11 family-interacting protein 5 (Rab11Fip5), one of the Rab11 effectors, in the immune system remain obscure. Our previous study demonstrated that RAB11FIP5 tra ... Full text Link to item Cite

After 62 years of regulating immunity, dexamethasone meets COVID-19.

Journal Article Nat Rev Immunol · October 2020 Six months into the COVID-19 pandemic, effective treatments have been frustratingly sparse. The RECOVERY clinical trial, however, revealed that treatment with dexamethasone, a classic synthetic glucocorticoid, enhanced survival of critically ill patients w ... Full text Link to item Cite

Murine Glucocorticoid Receptors Orchestrate B Cell Migration Selectively between Bone Marrow and Blood.

Journal Article J Immunol · August 1, 2020 Glucocorticoids promote CXCR4 expression by T cells, monocytes, macrophages, and eosinophils, but it is not known if glucocorticoids regulate CXCR4 in B cells. Considering the important contributions of CXCR4 to B cell development and function, we investig ... Full text Link to item Cite

Conditional antibody expression to avoid central B cell deletion in humanized HIV-1 vaccine mouse models.

Journal Article Proc Natl Acad Sci U S A · April 7, 2020 HIV-1 vaccine development aims to elicit broadly neutralizing antibodies (bnAbs) against diverse viral strains. In some HIV-1-infected individuals, bnAbs evolved from precursor antibodies through affinity maturation. To induce bnAbs, a vaccine must mediate ... Full text Link to item Cite

Immune checkpoint modulation enhances HIV-1 antibody induction.

Journal Article Nat Commun · February 19, 2020 Eliciting protective titers of HIV-1 broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development, but current vaccine strategies have yet to induce bnAbs in humans. Many bnAbs isolated from HIV-1-infected individuals are encoded by immun ... Full text Open Access Link to item Cite

Neonatal Rhesus Macaques Have Distinct Immune Cell Transcriptional Profiles following HIV Envelope Immunization.

Journal Article Cell Rep · February 4, 2020 HIV-1-infected infants develop broadly neutralizing antibodies (bnAbs) more rapidly than adults, suggesting differences in the neonatal versus adult responses to the HIV-1 envelope (Env). Here, trimeric forms of HIV-1 Env immunogens elicit increased gp120- ... Full text Open Access Link to item Cite

Targeted selection of HIV-specific antibody mutations by engineering B cell maturation.

Journal Article Science · December 6, 2019 INTRODUCTION: A major goal of HIV-1 vaccine development is the design of immunogens that induce broadly neutralizing antibodies (bnAbs). However, vaccination of humans has not resulted in the induction of affinity-matured and potent HIV-1 bnAbs. To devise ... Full text Link to item Cite

Simian-Human Immunodeficiency Virus SHIV.CH505-Infected Infant and Adult Rhesus Macaques Exhibit Similar Env-Specific Antibody Kinetics, despite Distinct T-Follicular Helper and Germinal Center B Cell Landscapes.

Journal Article J Virol · August 1, 2019 Global elimination of pediatric human immunodeficiency virus (HIV) infections will require the development of novel immune-based approaches, and understanding infant immunity to HIV is critical to guide the rational design of these intervention strategies. ... Full text Link to item Cite

Characterization of HIV-1 Nucleoside-Modified mRNA Vaccines in Rabbits and Rhesus Macaques.

Journal Article Mol Ther Nucleic Acids · April 15, 2019 Despite the enormous effort in the development of effective vaccines against HIV-1, no vaccine candidate has elicited broadly neutralizing antibodies in humans. Thus, generation of more effective anti-HIV vaccines is critically needed. Here we characterize ... Full text Link to item Cite

Endogenous glucocorticoids prevent gastric metaplasia by suppressing spontaneous inflammation.

Journal Article J Clin Invest · March 1, 2019 In the stomach, chronic inflammation causes metaplasia and creates a favorable environment for the evolution of gastric cancer. Glucocorticoids are steroid hormones that repress proinflammatory stimuli, but their role in the stomach is unknown. In this stu ... Full text Link to item Cite

RAB11FIP5 Expression and Altered Natural Killer Cell Function Are Associated with Induction of HIV Broadly Neutralizing Antibody Responses.

Journal Article Cell · October 4, 2018 HIV-1 broadly neutralizing antibodies (bnAbs) are difficult to induce with vaccines but are generated in ∼50% of HIV-1-infected individuals. Understanding the molecular mechanisms of host control of bnAb induction is critical to vaccine design. Here, we pe ... Full text Link to item Cite

Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses.

Journal Article J Exp Med · June 4, 2018 T follicular helper (Tfh) cells are required to develop germinal center (GC) responses and drive immunoglobulin class switch, affinity maturation, and long-term B cell memory. In this study, we characterize a recently developed vaccine platform, nucleoside ... Full text Link to item Cite

Vaccine Induction of Heterologous Tier 2 HIV-1 Neutralizing Antibodies in Animal Models.

Journal Article Cell Rep · December 26, 2017 The events required for the induction of broad neutralizing antibodies (bnAbs) following HIV-1 envelope (Env) vaccination are unknown, and their induction in animal models as proof of concept would be critical. Here, we describe the induction of plasma ant ... Full text Link to item Cite

Irgm1 coordinately regulates autoimmunity and host defense at select mucosal surfaces.

Journal Article JCI Insight · August 17, 2017 The pathogenesis of primary Sjogren's syndrome (SS), an autoimmune disease that targets the mucosa of exocrine tissues, is poorly understood. Although several mouse models have been developed that display features of SS, most of these are within the larger ... Full text Link to item Cite

Immune regulation by glucocorticoids.

Journal Article Nat Rev Immunol · April 2017 Endogenous glucocorticoids are crucial to various physiological processes, including metabolism, development and inflammation. Since 1948, synthetic glucocorticoids have been used to treat various immune-related disorders. The mechanisms that underlie the ... Full text Link to item Cite

The GS Protein-coupled A2a Adenosine Receptor Controls T Cell Help in the Germinal Center.

Journal Article J Biol Chem · January 27, 2017 T follicular helper (TFH) cells have been shown to be critically required for the germinal center (GC) reaction where B cells undergo class switch recombination and clonal selection to generate high affinity neutralizing antibodies. However, detailed knowl ... Full text Link to item Cite

Germinal Center Hypoxia Potentiates Immunoglobulin Class Switch Recombination.

Journal Article J Immunol · November 15, 2016 Germinal centers (GCs) are anatomic sites where B cells undergo secondary diversification to produce high-affinity, class-switched Abs. We hypothesized that proliferating B cells in GCs create a hypoxic microenvironment that governs their further different ... Full text Link to item Cite

T-cell development of resistance to apoptosis is driven by a metabolic shift in carbon source and altered activation of death pathways.

Journal Article Cell Death Differ · May 2016 We developed a model system to investigate apoptotic resistance in T cells using osmotic stress (OS) to drive selection of death-resistant cells. Exposure of S49 (Neo) T cells to multiple rounds of OS followed by recovery of surviving cells resulted in the ... Full text Link to item Cite

The Concise Guide to PHARMACOLOGY 2015/16: Overview.

Journal Article Br J Pharmacol · December 2015 The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), ... Full text Link to item Cite

Specificity and sensitivity of glucocorticoid signaling in health and disease.

Journal Article Best Pract Res Clin Endocrinol Metab · August 2015 Endogenous glucocorticoids regulate a variety of physiologic processes and are crucial to the systemic stress response. Glucocorticoid receptors are expressed throughout the body, but there is considerable heterogeneity in glucocorticoid sensitivity and in ... Full text Link to item Cite

Immunogenicity of membrane-bound HIV-1 gp41 membrane-proximal external region (MPER) segments is dominated by residue accessibility and modulated by stereochemistry.

Journal Article J Biol Chem · November 1, 2013 Structural characterization of epitope-paratope pairs has contributed to the understanding of antigenicity. By contrast, few structural studies relate to immunogenicity, the process of antigen-induced immune responses in vivo. Using a lipid-arrayed membran ... Full text Link to item Cite

Identification of a tissue-specific, C/EBPβ-dependent pathway of differentiation for murine peritoneal macrophages.

Journal Article J Immunol · November 1, 2013 Macrophages and dendritic cells (DC) are distributed throughout the body and play important roles in pathogen detection and tissue homeostasis. In tissues, resident macrophages exhibit distinct phenotypes and activities, yet the transcriptional pathways th ... 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 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

Disparate adjuvant properties among three formulations of "alum".

Journal Article Vaccine · January 11, 2013 Aluminum adjuvants, commonly referred to as "alum," are the most widespread immunostimulants in human vaccines. Although the mechanisms that promote humoral responses to alum-adsorbed antigens are still enigmatic, alum is thought to form antigen depots and ... Full text Link to item Cite

NUR who? An orphan transcription factor holds promise for monomaniacs.

Journal Article Nat Immunol · July 19, 2011 Full text Link to item Cite

Activation-induced cytidine deaminase mediates central tolerance in B cells.

Journal Article Proc Natl Acad Sci U S A · July 12, 2011 The Aicda gene product, activation-induced cytidine deaminase (AID), initiates somatic hypermutation, class-switch recombination, and gene conversion of Ig genes by the deamination of deoxycytidine, followed by error-prone mismatch- or base-excision DNA re ... Full text Link to item Cite

Inflammation triggers emergency granulopoiesis through a density-dependent feedback mechanism.

Journal Article PLoS One · 2011 Normally, neutrophil pools are maintained by homeostatic mechanisms that require the transcription factor C/EBPα. Inflammation, however, induces neutrophilia through a distinct pathway of "emergency" granulopoiesis that is dependent on C/EBPβ. Here, we sho ... Full text Open Access Link to item Cite

A new guise for hyper-IgM syndrome.

Journal Article Blood · December 23, 2010 Full text Link to item Cite

Distinct granuloma responses in C57BL/6J and BALB/cByJ mice in response to pristane.

Journal Article Int J Exp Pathol · October 2010 Granuloma formation is an inflammatory response of the host against invading pathogens or indigestible substances. We generated mesenteric oil granulomas by injecting pristane into the peritoneal cavity (PC) of mice, and compared oil granuloma formation in ... Full text Link to item Cite

Surfactant protein-A inhibits mycoplasma-induced dendritic cell maturation through regulation of HMGB-1 cytokine activity.

Journal Article J Immunol · October 1, 2010 During pulmonary infections, a careful balance between activation of protective host defense mechanisms and potentially injurious inflammatory processes must be maintained. Surfactant protein A (SP-A) is an immune modulator that increases pathogen uptake a ... Full text Link to item Cite

IL-1R type I-dependent hemopoietic stem cell proliferation is necessary for inflammatory granulopoiesis and reactive neutrophilia.

Journal Article J Immunol · May 15, 2009 Infections and inflammation trigger neutrophilias that are supported by a hematopoietic program of accelerated granulopoiesis known as emergency granulopoiesis. The intrinsic factors that drive reactive neutrophilias and emergency granulopoiesis have been ... Full text Link to item Cite

Effects of acute and chronic inflammation on B-cell development and differentiation.

Journal Article J Invest Dermatol · February 2009 Recently, our understanding of hematopoiesis and the development of the immune system has fundamentally changed, leading to significant discoveries with important clinical relevance. Hematopoiesis, once described in terms of irreversible and discrete devel ... Full text Link to item Cite

Ex vivo glycan engineering of CD44 programs human multipotent mesenchymal stromal cell trafficking to bone.

Journal Article Nat Med · February 2008 The capacity to direct migration ('homing') of blood-borne cells to a predetermined anatomic compartment is vital to stem cell-based tissue engineering and other adoptive cellular therapies. Although multipotent mesenchymal stromal cells (MSCs, also termed ... Full text Link to item Cite

Shear flow-dependent integration of apical and subendothelial chemokines in T-cell transmigration: implications for locomotion and the multistep paradigm.

Journal Article Blood · February 15, 2007 Lymphocyte extravasation requires that emigrating cells process chemoattractant signals, typically mediated by chemokines, encountered on endothelial surface (apical) and subendothelial (basal) compartments. These signals are delivered under conditions of ... Full text Link to item Cite

The peritoneal cavity provides a protective niche for B1 and conventional B lymphocytes during anti-CD20 immunotherapy in mice.

Journal Article J Immunol · April 1, 2005 Although anti-CD20 immunotherapy effectively treats human lymphoma and autoimmune disease, the in vivo effect of immunotherapy on tissue B cells and their subsets is generally unknown. To address this, anti-mouse CD20 mAbs were used in a mouse model in whi ... Full text Link to item Cite