A5019180077- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- Neonatal Respiratory Health Research
- SARS-CoV-2 and COVID-19 Research
- Immune responses and vaccinations
- Hemophilia Treatment and Research
- T-cell and B-cell Immunology
- Platelet Disorders and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Complement system in diseases
- Immune Cell Function and Interaction
- Respiratory viral infections research
- interferon and immune responses
- COVID-19 Clinical Research Studies
- Influenza Virus Research Studies
- Pneumonia and Respiratory Infections
- Epigenetics and DNA Methylation
- Immunodeficiency and Autoimmune Disorders
- CAR-T cell therapy research
- Immune cells in cancer
- vaccines and immunoinformatics approaches
- COVID-19 Impact on Reproduction
- Diabetes and associated disorders
- Chronic Myeloid Leukemia Treatments
- Tuberculosis Research and Epidemiology
Boston Children's Hospital
2016-2025
Harvard University
2014-2024
The Coordinating Center
2024
Princess Margaret Hospital for Children
2024
The University of Western Australia
2024
Boston Children's Museum
2021
Lemuel Shattuck Hospital
2016
Sanquin
2007-2013
Fats and Proteins Research Foundation
2013
University of Amsterdam
2011
Systems biology can unravel complex but has not been extensively applied to human newborns, a group highly vulnerable wide range of diseases. We optimized methods extract transcriptomic, proteomic, metabolomic, cytokine/chemokine, and single cell immune phenotyping data from <1 ml blood, volume readily obtained newborns. Indexing baseline applying innovative integrative computational reveals dramatic changes along remarkably stable developmental trajectory over the first week life. This is...
Global deployment of vaccines that can provide protection across several age groups is still urgently needed to end the COVID-19 pandemic, especially in low- and middle-income countries. Although against SARS-CoV-2 based on mRNA adenoviral vector technologies have been rapidly developed, additional practical scalable are required meet global demand. Protein subunit formulated with appropriate adjuvants represent an approach address this urgent need. The receptor binding domain (RBD) a key...
STAT family members have been implicated in regulating the balance between B cell lymphoma (BCL)6 and lymphocyte induced maturation protein (BLIMP)1 to control plasma differentiation. We previously showed that STAT5 induces BCL6 block differentiation extend life span of human cells. The heterogeneity activation by cytokines their effects on prompted us investigate effect STAT3 First stimulation with IL-21, which promotes differentiation, robust prolonged primary then investigated direct...
Newborns display distinct immune responses, leaving them vulnerable to infections and impairing immunization. Targeting newborn dendritic cells (DCs), which integrate vaccine signals into adaptive might enable development of age-specific formulations overcome suboptimal immunization.Small-molecule imidazoquinoline Toll-like receptor (TLR) 8 agonists robustly activate DCs but can result in reactogenicity when delivered soluble form. We used rational engineering age- species-specific modeling...
Neonatal administration of BCG vaccine rapidly increases neutrophil production to reduce mortality from sepsis.
Infection is the most common cause of mortality in early life, and immunization promising biomedical intervention to reduce this burden. However, newborns fail respond optimally vaccines. Adjuvantation a key approach enhancing vaccine immunogenicity, but responses human newborn leukocytes candidate adjuvants, including TLR agonists, are functionally distinct. Herein, we demonstrate that 3M-052 locally acting lipidated imidazoquinoline TLR7/8 agonist adjuvant mice, which, when properly...
Bacille Calmette-Guérin (BCG), the live attenuated tuberculosis vaccine, is manufactured under different conditions across globe generating formulations that may differ in clinical efficacy. Innate immune recognition of BCG contributes to immunogenicity suggesting differences viability contribute divergent activity licensed formulations.We compared BCG-Denmark (DEN), -Japan (JPN), -India (IND), -Bulgaria (BUL) and -USA vitro with respect a) as measured by colony-forming units (CFU),...
Abstract Due to functionally distinct cell-mediated immunity, newborns and infants are highly susceptible infection with intracellular pathogens. Indeed, neonatal Ag-presenting dendritic cells (DCs) demonstrate impaired Th1 responses many candidate adjuvants, including most TLR agonists (TLRAs). Combination adjuvantation systems may provide enhanced immune activation but have typically been developed without regard the age of target population. We posited that combinations TLRAs C-type...
Activation of T-helper cells is dependent upon the appropriate presentation antigen-derived peptides on MHC class II molecules expressed antigen presenting cells. In current study we explored repertoire presented human monocyte derived dendritic (moDCs) from four HLA-typed healthy donors. II-bound could be routinely recovered small cultures containing 5 × 10(6) A fraction identified were proteins localized in plasma membrane, endosomes, and lysosomes, but majority that originate other...
Adjuvants are vaccine components that can boost the type, magnitude, breadth, and durability of an immune response. We have previously demonstrated certain adjuvant combinations act synergistically to enhance shape immunogenicity including promotion Th1 cytotoxic T-cell development. These also promoted protective immunity in vulnerable populations such as newborns. In this study, we employed combined antigen-specific human vitro models identify could promote expansion vaccine-specific CD4+...
Background Newborns and young infants are at higher risk for infections than adults, manifest suboptimal vaccine responses, motivating a search novel immunomodulators and/or adjuvants effective in early life. In contrast to most TLR agonists (TLRA), TLR8 such as imidazoquinolines (IMQs) induce adult-level Th1-polarizing cytokine production from human neonatal cord blood monocytes candidate life adjuvants. We assessed whether TLR8-activating IMQ congeners may differ potency efficacy inducing...
Vaccines have generally been developed with limited insight into their molecular impact. While systems vaccinology enables characterization of mechanisms action, these tools yet to be applied infants, who are at high risk infection and receive the most vaccines. Bacille Calmette-Guérin (BCG) protects infants against disseminated tuberculosis (TB) TB-unrelated infections via incompletely understood mechanisms. We employ mass-spectrometry-based metabolomics blood plasma profile BCG-induced...
Abstract Respiratory syncytial virus is a leading cause of morbidity and mortality in children, due part to their distinct immune system, characterized by impaired induction Th 1 immunity. Here we show application cationic adjuvant formulation CAF08, liposomal vaccine tailored induce immunity early life via synergistic engagement Toll-like Receptor 7/8 the C-type lectin receptor Mincle. We apply quantitative phosphoproteomics human dendritic cells reveal role for Protein Kinase C-δ enhanced...
Neonatal innate immunity is distinct from that of adults, which may contribute to increased susceptibility infection and limit vaccine responses. B cells play critical roles in protection detect PAMPs via TLRs, that, when co-activated with CD40, can drive B-cell proliferation Ab production. We characterized the expression TLRs circulating newborns evaluated TLR- CD40-mediated naïve class-switch recombination (CSR) cytokine Gene levels most was similar between newborn adult cells, except...
Neonates have heightened susceptibility to infections. The biological mechanisms are incompletely understood but thought be related age-specific adaptations in immunity due resource constraints during immune system development and growth. We present here an extended analysis of our proteomics study peripheral blood-plasma from a healthy full-term newborns delivered vaginally, collected at the day birth on life (DOL) 1, 3, or 7, cover first week life. plasma proteome was characterized by...