RECOMBINANT BCG MALARIA VACCINES

Project: Research project

Project Details

Description

DESCRIPTION: (Adapted from Applicant's Abstract) Malaria is a major global
health burden with annual incidences of 300 to 500 million cases and 1.5 to 2.7
million deaths per year. Development of a vaccine represents an essential goal
for an effective control strategy. However, for a vaccine to have a significant
impact it would need to be safe, easy to administer, effective in children and
affordable in Africa. This laboratory has developed the systems to engineer
BCG, the widely used tuberculosis vaccine into a recombinant BCG (rBCG) vaccine
vector capable of expressing foreign antigens. Immunization with rBCG
expressing viral, bacterial, or parasitic foreign antigens elicits antibody as
well as CD4 and CD8 T cell responses to the foreign antigens in mice and
monkeys. Recombinant BCG represents an attractive vaccine delivery system for
Africa as BCG is a safe, inexpensive vaccine that is already administered to
the majority of children at birth throughout Africa and the developing world.
Previous studies have shown that immunization with the conserved antigen MSP-1
from a variety of Plasmodium species protects against challenge with the
homologous Plasmodium species in mouse and monkey models. We have obtained
expression of the conserved portion of the Plasmodium falciparum blood stage
antigen MSP-1 on the surface of BCG. These expression constructs have been
engineered into vectors that contain a gene that complements novel auxotrophic
deletion mutations of BCG, to provide a selection system to maintain the
plasmids when grown in mammalian hosts. We intend to express MSP-1 antigens of
P. yoelii and P. knowlesi in these systems and then test the ability of all of
the rBCG constructs to protect against malaria in mice, Aotus monkeys, and
Rhesus monkeys. The immunization studies are designed to test the recombinant
BCG's expressing MSP-1 for protection and their abilities to induce a priming
immunization that can confer protection upon infection with the malarial
parasites.
StatusFinished
Effective start/end date8/15/997/31/03

ASJC

  • Infectious Diseases
  • Immunology