Derek W. Cain
A5057722534- HIV Research and Treatment
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- vaccines and immunoinformatics approaches
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cytomegalovirus and herpesvirus research
- RNA Interference and Gene Delivery
- Cell Adhesion Molecules Research
- Chemokine receptors and signaling
- Estrogen and related hormone effects
- Viral gastroenteritis research and epidemiology
- Animal Virus Infections Studies
- COVID-19 Clinical Research Studies
- Adrenal Hormones and Disorders
- Immunodeficiency and Autoimmune Disorders
- Mesenchymal stem cell research
- Blood disorders and treatments
- Macrophage Migration Inhibitory Factor
- Viral Infections and Outbreaks Research
- Neutropenia and Cancer Infections
- Phagocytosis and Immune Regulation
Duke University
2016-2025
Duke Medical Center
2005-2024
International Vaccine Institute
2013-2023
National Institutes of Health
2015-2023
Durham Technical Community College
2022
Duke University Hospital
2005-2022
National Institute of Environmental Health Sciences
2015-2020
Emory University
2011
Harvard University
2006-2008
Brigham and Women's Hospital
2006-2008
T follicular helper (Tfh) cells are required to develop germinal center (GC) responses and drive immunoglobulin class switch, affinity maturation, long-term B cell memory. In this study, we characterize a recently developed vaccine platform, nucleoside-modified, purified mRNA encapsulated in lipid nanoparticles (mRNA-LNPs), that induces high levels of Tfh GC cells. Intradermal vaccination with nucleoside-modified mRNA-LNPs encoding various viral surface antigens elicited polyfunctional,...
Engineering better bnAbs A highly effective HIV vaccine has been the goal of vaccinologists for nearly 35 years. successful would need to induce broadly neutralizing antibodies (bnAbs) that are capable multiple strains (see Perspective by Agazio and Torres). Steichen et al. report a strategy in which first shot can lead immune responses generate desired bnAbs. By combining knowledge human antibody repertoires structure guide design, they validated candidate immunogens through functional...
A critical roadblock to HIV vaccine development is the inability induce B cell lineages of broadly neutralizing antibodies (bnAbs) in humans. In people living with HIV-1, bnAbs take years develop. The HVTN 133 clinical trial studied a peptide/liposome immunogen targeting HIV-1 envelope (Env) membrane-proximal external region (MPER) (NCT03934541). Here, we report MPER peptide-liposome induction polyclonal mature and their precursors, most potent which neutralized 15% global tier 2 strains 35%...
Although anti-CD20 immunotherapy effectively treats human lymphoma and autoimmune disease, the in vivo effect of on tissue B cells their subsets is generally unknown. To address this, anti-mouse CD20 mAbs were used a mouse model which extent kinetics cell depletion could be assessed vivo. mAb treatment depleted most mature within 2 days, with 95-98% bone marrow, blood, spleen, lymph nodes, gut-associated lymphoid tissues by day 7, including marginal zone follicular cells. The few spleen...
Many human monoclonal antibodies that neutralize multiple clades of HIV-1 are polyreactive and bind avidly to mammalian autoantigens. Indeed, the generation neutralizing 2F5 4E10 epitopes gp41 in man may be proscribed by immune tolerance because mice expressing VH VL regions have a block B cell development is characteristic central tolerance. This developmental blockade implies presence tolerizing autoantigens mimicked membrane-proximal external region gp41. We identify kynureninase (KYNU)...
Macrophages and dendritic cells (DC) are distributed throughout the body play important roles in pathogen detection tissue homeostasis. In tissues, resident macrophages exhibit distinct phenotypes activities, yet transcriptional pathways that specify tissue-specific largely unknown. We investigated functions origins of two peritoneal macrophage populations mice: small large (SPM LPM, respectively). SPM LPM differ their ability to phagocytose apoptotic cells, as well production cytokines...
Abstract Germinal centers (GCs) are anatomic sites where B cells undergo secondary diversification to produce high-affinity, class-switched Abs. We hypothesized that proliferating in GCs create a hypoxic microenvironment governs their further differentiation. Using molecular markers, we found be predominantly hypoxic. Compared normoxia (21% O2), culture conditions (1% O2) vitro accelerated class switching and plasma cell formation enhanced expression of GL-7 on CD4+ T cells. Reversal GC...
Highlights•HIV-1 vaccine-induced broadly neutralizing antibodies targeted the V1V2-glycan site•V1V2-glycan arose when host factors limited CD4 binding site antibodies•V-region secondary rearrangement was a mechanism for generating antibodiesSummaryThe events required induction of broad (bnAbs) following HIV-1 envelope (Env) vaccination are unknown, and their in animal models as proof concept would be critical. Here, we describe plasma capable heterologous primary (tier 2) strains one macaque...
Despite the enormous effort in development of effective vaccines against HIV-1, no vaccine candidate has elicited broadly neutralizing antibodies humans. Thus, generation more anti-HIV is critically needed. Here we characterize immune responses induced by nucleoside-modified and purified mRNA-lipid nanoparticle (mRNA-LNP) encoding clade C transmitted/founder HIV-1 envelope (Env) 1086C. Intradermal vaccination with 1086C Env mRNA-LNPs high levels gp120-specific rabbits rhesus macaques....
HIV-1 broadly neutralizing antibodies (bnAbs) are difficult to induce with vaccines but generated in ∼50% of HIV-1-infected individuals. Understanding the molecular mechanisms host control bnAb induction is critical vaccine design. Here, we performed a transcriptome analysis blood mononuclear cells from 47 individuals who made bnAbs and 46 did not identified upregulation RAB11FIP5, encoding Rab effector protein associated recycling endosomes. Natural killer (NK) had highest differential...
Summary SARS-CoV-2 neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding is whether they mediate disease enhancement. Here, we isolated NAbs the receptor-binding domain (RBD) and N-terminal (NTD) of spike from individuals with acute or convalescent a history SARS-CoV-1 infection. Cryo-electron microscopy RBD NTD demonstrated function-specific modes binding. Select also Fc receptor-γ (FcγR)-mediated enhancement virus infection in vitro , while five non-neutralizing...
Abstract Coronavirus vaccines that are highly effective against current and anticipated SARS-CoV-2 variants needed to control COVID-19. We previously reported a receptor-binding domain (RBD)-sortase A-conjugated ferritin nanoparticle (scNP) vaccine induced neutralizing antibodies pre-emergent sarbecoviruses protected non-human primates (NHPs) from WA-1 infection. Here, we find the RBD-scNP in NHPs pseudoviruses of SARS-CoV including 614G, Beta, Delta, Omicron BA.1, BA.2, BA.2.12.1,...
Infections and inflammation trigger neutrophilias that are supported by a hematopoietic program of accelerated granulopoiesis known as emergency granulopoiesis. The intrinsic factors drive reactive have been inferred but not demonstrated. Here, we show alum cannot elicit in IL-1R type I (IL-1RI)(-/-) mice, whereas other inflammatory responses, including eosinophilia Ab production, remain intact. Analysis this specific impairment revealed an unanticipated role for IL-1RI supporting increased...
The Aicda gene product, activation-induced cytidine deaminase (AID), initiates somatic hypermutation, class-switch recombination, and conversion of Ig genes by the deamination deoxycytidine, followed error-prone mismatch- or base-excision DNA repair. These processes are crucial for generation genetically diverse, high affinity antibody robust humoral immunity, but exact significant genetic damage promote cell death. In mice, physiologically AID expression was thought to be restricted...
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 is dependent on C/EBPβ. Here, we show in mice alum triggers emergency IL-1RI-dependent induction G-CSF. G-CSF/G-CSF-R neutralization impairs proliferative responses hematopoietic stem and progenitor cells (HSPC) to alum, but also abrogates acute mobilization BM neutrophils,...