A5024848676- Immunodeficiency and Autoimmune Disorders
- Pneumonia and Respiratory Infections
- Immunotherapy and Immune Responses
- HIV Research and Treatment
- T-cell and B-cell Immunology
- Pneumocystis jirovecii pneumonia detection and treatment
- Immune Cell Function and Interaction
- Diabetes and associated disorders
- Monoclonal and Polyclonal Antibodies Research
- Malaria Research and Control
- Animal Virus Infections Studies
- Viral gastroenteritis research and epidemiology
- Respiratory viral infections research
- Glycosylation and Glycoproteins Research
- Blood groups and transfusion
- Mosquito-borne diseases and control
- Viral Infections and Outbreaks Research
- Complement system in diseases
- Hepatitis B Virus Studies
- Bacterial Infections and Vaccines
- SARS-CoV-2 and COVID-19 Research
- Virology and Viral Diseases
- Cytomegalovirus and herpesvirus research
- vaccines and immunoinformatics approaches
- Viral Infections and Vectors
National Institutes of Health
2017-2024
National Institute of Allergy and Infectious Diseases
2017-2024
Walter Reed Army Institute of Research
2023-2024
University of Toledo
2012-2016
Wayne State University
2008
Broadly neutralizing antibodies (bnAbs) can protect against HIV infection but have not been induced by human vaccination. A key barrier to bnAb induction is vaccine priming of rare bnAb-precursor B cells. In a randomized, double-blind, placebo-controlled phase 1 clinical trial, the vaccine-priming candidate eOD-GT8 60mer adjuvanted with AS01
The engineered outer domain germline targeting version 8 (eOD-GT8) 60-mer nanoparticle was designed to prime VRC01-class HIV-specific B cells that would need be matured, through additional heterologous immunizations, into are able produce broadly neutralizing antibodies. CD4 T cell help will critical for the development of such high-affinity antibody responses. Thus, we assessed induction and epitope specificities vaccine-specific from IAVI G001 phase 1 clinical trial tested immunization...
Vaccine priming immunogens that activate germline precursors for broadly neutralizing antibodies (bnAbs) have promise development of precision vaccines against major human pathogens. In a clinical trial the eOD-GT8 60mer germline-targeting immunogen, higher frequencies vaccine-induced VRC01-class bnAb-precursor B cells were observed in high dose compared to low group. Through immunoglobulin heavy chain variable (IGHV) genotyping, statistical modeling, quantification IGHV1-2 allele usage and...
Durable humoral immunity is mediated by long-lived plasma cells (LLPCs) that reside in the bone marrow. It remains unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein vaccination able to elicit and maintain LLPCs. Here, we describe a sensitive method identify isolate antigen-specific LLPCs tethering antibodies secreted these onto cell surface. Using this method, found two doses of adjuvanted SARS-CoV-2 are induce protein–specific LLPC reservoirs...
The phenotype of B cells that respond to vaccination with the purified pneumococcal polysaccharide (PPS) has been a topic debate. We have recently identified from healthy young volunteers as CD27+IgM+ cells. However, PPS-responding B-cell population not yet in high-risk populations, such elderly individuals. Previous studies shown individuals lower percentage immunoglobulin M memory than adults. In this study, we directly characterized PPS-specific before and after PPS vaccine (PPV) adults,...
Zika virus (ZIKV) is an emerging pathogen that causes devastating congenital defects. The overlapping epidemiology and immunologic cross-reactivity between ZIKV dengue (DENV) pose complex challenges to vaccine design, given the potential for antibody-dependent enhancement of disease. Therefore, classification ZIKV-specific antibody targets notable value. From a ZIKV-infected rhesus macaque, we identify ZIKV-reactive B cells isolate potent neutralizing monoclonal antibodies (mAbs) with no...
Abstract Vaccine priming immunogens that activate germline precursors for broadly neutralizing antibodies (bnAbs) have promise development of precision vaccines against major human pathogens. In a clinical trial the eOD-GT8 60mer germline-targeting immunogen, higher frequencies vaccine-induced VRC01-class bnAb-precursor B cells were observed in high dose compared to low group. Through immunoglobulin heavy chain variable (IGHV) genotyping, statistical modeling, quantification IGHV1-2 allele...
Newly diagnosed HIV-positive individuals are 35 to 100-fold more susceptible Streptococcus pneumoniae infection compared non-infected individuals. Therefore, the 23-valent pneumococcal polysaccharide vaccine (PPV23) has previously been recommended, though efficacy and effectiveness of vaccination remains controversial. Early severe B cell dysfunction is a central feature HIV infection. The specific nature immune cells involved in production protective antigen-specific antibodies be...
Streptococcus pneumoniae continues to cause serious infections in HIV-positive individuals the era of highly active anti-retroviral therapy. This led recommendation revaccinate with PPV23 five years after primary vaccination. The benefits revaccination and impact long term therapy (HAART) on antigen-specific B cell reconstitution have remained unclear thus far were investigated.We assessed antibody levels, opsonophagocytic activity phenotype pneumococcal polysaccharide (PPS) specific-B cells...
Cytokines have been used extensively as adjuvants in vaccines. However, practical considerations limit their use; diffusion from antigen, short half-lives and additional production costs. To address these problems we developed a technology that efficiently produces inactivated, whole-virus influenza vaccine bearing membrane-bound cytokines. provide "proof of principle," chose chicken interleukin-2 (IL-2) granulocyte-macrophage colony-stimulating factor. Fusion constructs were generated which...
The number of aging human immunodeficiency virus-infected (HIV+) individuals living in the United States has substantially grown over past two decades. Advanced age and HIV infection both increase susceptibility to Streptococcus pneumoniae due B cell dysfunction. combined impact these factors on pneumococcal vaccine responses remains unknown.We assessed serum immunoglobulin (Ig) G IgM levels opsonophagocytic killing assay (OPA) titers serotypes 14 23F HIV+ subjects HIV-uninfected (HIV-)...
Shorter prophylactic vaccine schedules may offer more rapid protection against Ebola in resource-limited settings.
Background Members of the Tumor Necrosis Factor (TNF)-superfamily have speculated roles in response against T-independent type II antigens (TI-II) including pneumococcal polysaccharides (PPS). Dysregulation their expression is associated with an enhanced risk for disease neonates but other high-risk populations HIV-positive individuals remains to be elucidated. Objective To investigate signals that contribute towards PPS-response and identify potential anomalies may account diminished...
Abstract The RV144 HIV-1 vaccine trial has been the only clinical to date that shown any degree of efficacy and associated with presence vaccine-elicited envelope-specific binding antibody CD4+ T-cell responses. This also showed a vector-prime protein boost combined strategy was better than when used alone. Here we have studied three different priming vectors—plasmid DNA, recombinant MVA, VSV, all encoding clade C transmitted/founder Env 1086 gp140, for groups six non-human primates each,...
Natural antibodies serve as the body’s first line of defense against pneumococcal challenge. Polyreactive human polysaccharide IgG have not been extensively studied. We analyzed polyreactive that bind multiple polysaccharides, including PPS14 and PPS23F. These were isolated from single specific B cells allowing for analysis immunoglobulins with natively paired variable regions. Although individually, these demonstrated similar characteristics. Most possessed a light chain CDR3 length made up...
The lymph node (LN) is a critical biological site for immune maturation after vaccination as it includes several cell populations priming the antibody response. Here, we present protocol sampling LN and isolating to evaluate immunogens targeting germline cells. We describe steps media tube preparation sample collection using an ultrasound-guided fine-needle aspiration procedure. This safe, quick, low-cost, less invasive than excisional biopsy. For complete details on use execution of this...
Abstract HIV infection is characterized by profound changes in the B cell compartment, which includes, impaired antigen specific response and a significant loss of IgM memory cells, amongst other defects. Despite HAART’s success reducing incidence opportunistic infections, invasive pneumococcal disease infected population continues to be high. PPV-23 vaccine recommended as prophylactic measure HAART treated population; however, its serological benefit currently unclear. Although, has been...
Abstract The peripheral blood of newly diagnosed HIV infected individuals is subjected to high uncontrolled viral titers. decimation both T and B cells thus leaves these highly susceptible opportunistic infections, including Streptococcus pneumoniae, despite the availability vaccines. We have previously shown using directly labeled fluorescent pneumococcal polysaccharides that majority polysaccharide-specific in healthy were IgM+ memory cells. Using this method, we identified specific...