TESTING MUCOSAL VACCINES IN AN ANIMAL MEASLES MODEL

  • Stephensen, Charles Bolt (PI)

Project: Research project

Project Details

Description

Measles, given the appropriate vaccine, is an eradicable disease. Problems
with both fixed and live-virus vaccines have created interest in new
approaches to measles vaccination. New vaccines should be effective when
administered in the presence of maternal antibody because early
immunization is essential in endemic settings. An impediment (perhaps more
illusory than real) to testing new vaccine strategies has been that non-
primate, laboratory animals do not develop a measles-like illness when
inoculated with measles virus. However, canine distemper virus (CDV), a
morbillivirus and thus a close relative of measles virus, does produce a
measles-like infection in ferrets, a natural host of CDV: CDV is spread by
the same route, infects the same target cells, causes a similar
disseminated disease, and protection against reinfection is conferred by
immunization with the same virus structural proteins (the fusion [F] and
hemagglutinin [HA] proteins) as with measles. In addition, young ferrets
are naturally protected against CDV infection by maternal antibody. In
short, CDV is an ideal model for testing new morbillivirus vaccine
strategies. Our long-term goal is to develop an effective measles vaccine
that can be safely administered to all age groups. We will develop
candidate vaccines for CDV suitable for mucosal and parenteral
administration using the HA, F and N proteins. The mucosal route will be
explored as a means to avoid the inhibitory effects of maternal antibody.
We will develop recombinant vaccinia viruses for this purpose. We will
also purify F and HA by affinity chromatography for parenteral and mucosal
administration with the cholera-toxin binding-subunit (CTB) as an
adjuvant, and for preparation of ISCOMs. We will then determine the
protective efficacy of these candidate vaccines in immunologically naive
ferrets and in infant ferrets protected by maternal antibody. The
contribution of mucosal and serum antibody to protection will be assessed
by measuring total, HA- and F-specific serum and secretory antibody,
virus-neutralization and fusion inhibition. We will also determine if F-,
HA- and N-specific ferret antibodies will enhance infection of ferret
macrophages in vitro, a principal target cell of CDV in vivo, because such
enhancement could affect vaccination strategy and may have been a factor
in the development of atypical measles after administration of formalin-
fixed measles vaccines.
StatusFinished
Effective start/end date9/30/938/31/96

Funding

  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)

Fingerprint Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.