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Neonatal Immunization against Pertussis

Research Team

  • Technicians:  Jill van Kessel, Rachelle Buchanan, Stacy Strom
  •  Post-doctoral fellows:  Gael Auray,Srinivas Garlapati,Tadele Gebroyohannes,
  • Graduate students:  Aleksandra Gracia, Tova Dybvig, Monika Polewicz, Marina Facci
  • Project manager:  Jim Holmstrom

 

Overview

Infectious diseases remain the main cause of neonatal morbidity and mortality in both humans and animals. Thus, novel types of vaccines are urgently needed to induce protective immunity early in life. Such vaccines, however, have to overcome several challenges including the immaturity of the immune system, its bias towards a Th2 type immune response and the potential interference with maternally-derived antibodies. The aim of this project is to develop novel vaccine formulations that will overcome these challenges and that will induce protective immunity response in the newborn even in the presence of maternally-derived antibodies.

We are using pertussis (whooping cough) as proof-of principle diseases. Our research is focused on (i) developing relevant animal models that simulate neonatal immune responses in humans, (ii) develop novel vaccine formulations and delivery strategies that can be used to immunize the neonate, (iii) study the transfer of maternal immunity from the mother to the offspring and determine whether mucosal immunization of the mother can enhance this transfer, (iv) develop immunization strategies that can help to overcome the interference with maternal immunity, (v) evaluate strategies to immunze the fetus in utero, (vi) and finally, study the basic mechanisms of mucosal immunity such as the role of innate immunity at the mucosal surfaces, antigen-uptake and immune induction, and the distribution of effector cells following immunization.


Objectives

  1. To develop novel vaccine platforms for neonatal vaccines, in particular for pertussis.
  2. To develop strategies to induce mucosal immune responses in the newborn.
  3. To investigate the potential of maternal immunization and analyze the transfer of secretory immunity from mother to child.
  4. To evaluate novel strategies for in utero immunization.
  5. To identify the role of innate immunity in the upper respiratory tract (ie. host defense peptides).
  6. To develop means of overcoming interference with maternal antibodies.
  7. To study antigen-uptake, induction of local immunity and migration of mucosal effector cells.
  8. To analyze the role of chemokines in lymphocyte trafficking at the mucosal surfaces.


Future Direction

  1. The future goals of this program are to develop vaccine technologies that can be used for a wide variety of pathogens in neonates. While initially focusing on pertussis , the goal is to develop a platform technology that can be used early in life, that is effective after a single-immunization and that provides strong systemic and mucosal immunity with a shift towards Th1-type immune responses. Microspheres will be used for vaccine delivery. To address interference with maternal immunization our newly developed vaccine formulations will be tested in nenonatal pigs in the presence of maternal antibodies.
  2. To further evaluate the potential of in utero vaccination using a variety of vaccine strategies.
  3. To further study the porcine immune system, in particular the mucosal immune system. We are interested in further studying the role of dendritic cells, regulatory T cells and mast cells in neonates and adults.

Funding Partners