Current Environment:

Overview

 

The Levy Lab's research focuses on the ontogeny of innate and adaptive immunity as it impacts age-specific vaccinology. 

Lab’s Current Projects

Adjuvant Discovery Program

  • Funding: NIH (NIAID)
  • Project Leader: David Dowling, PhD
  • Description: Small molecule screen vs human leukocytes to ID new adjuvants active vs newborns and elderly
  • Comment: This $10 million contract is generating lead adjuvants for enabling efficient immunization in early life and in the elderly. It is also generating substantial IP for BCH/TIDO. 

Development and validation of a neonatal tissue construct

  • Funding: Gates Foundation
  • Project Leader: Guzman Sanchez-Schmitz, MSc, PhD
  • Description: Microphysiologic tissue engineering to model age-specific vaccine-induced immune responses in vitro
  • Comment: Cutting edge in vitro platform to accelerate and de-risk age-specific vaccine development

Dissecting the mechanism of age-specific adjuvant synergy in vitro and in vivo

  • Funding: NIH (NIAID), U01 MMCA (Molecular mechanism of Combination Adjuvants).
  • Project Leader: Simon van Haren, PhD
  • Description: The aim of this project is to characterize the mechanisms underlying the synergistic activity of a recently identified agonist combination. R848 (activates Toll-like Receptors 7/8) and Trehalose-6,6-dibehenate (TDB, activates the C-type Lectin Receptor Mincle) are able to synergistically induce Th1 immunity in newborn cells. In this project we will evaluate the ability of this agonist combination to induce protective immune responses against Respiratory Syncitial Virus (RSV), using RSV pre-fusion protein as a model antigen.
  • Comment: The unique age-specific synergy between specific Toll-like Receptor-C-type Lectin receptor agonist combinations suggests a new paradigm for identification of adjuvantation systems tailored to enhance development of early life vaccines.

Identification of Innate and Adaptive Immune Pathway Defects in the Preterm Newborn 

  • Funding: BCH-DOM funds to the Precision Vaccines Program
  • Project Leader: Annette Scheid, MD
  • Description: The aim of this project is to identify potential targets of immunomodulatory therapies to prevent and treat infection in the preterm newborn and infant. Ultimately, we hope to contribute to optimization of tailored vaccines for the preterm as well as immunomodulatory therapies for the septic preterm. 
  • Comment: Sepsis remains one of the leading causes of mortality in the preterm. New therapeutic modalities to prophylactically prevent and treat sepsis are urgently needed for this vulnerable population.

 

 

 

 

 

 

MBL

 

 

  • Funding: Shire
  • Project Leader: Annette Scheid, MD
  • Description: Use of Levy Lab in vitro blood assay to determine whether addition of recombinant MBL enhances microbicidal activity of newborn blood tested in vitro
  • Comment: Preclinical /translational project to inform/de-risk a human clinical trial

 

 

 

 

 

 

 

 

 

Modeling of BCG responses

 

  • Funding: BCH-DOM funds to the Precision Vaccines Program
  • Project Leader: Asimenia Angelidou, MD, PhD, Simon van Haren, PhD, Guzman Sanchez Schmitz, MSc, PhD
  • Description: Comparison of the innate immune activating effects of distinct formulations of BCG vaccines
  • Comment: BCG is the most commonly given vaccine in the world yet its production is variable leading to heterogeneity of immune effects that are poorly understood

 

Technology Development Fund

  • Funding: BCH (TIDO)
  • Project Leader: Guzman Sanchez-Schmitz, MSc, PhD
  • Description: PCV13 vs. Pneumovax peptide Ag- specific CD4 T cell responses 
  • Comment: Effort to validate that that the in vitro tissue construct demonstrates reduced responses for vaccines that are poorly immunogenic in the newborn