Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 33, Pages 11581-11588Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0504592102
Keywords
cellular immunity; interferon-gamma; vaccine; protective immunity
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Funding
- NIAID NIH HHS [AI07541, R01 AI35149, T32 AI07417, T32 AI007417] Funding Source: Medline
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Measles remains a major worldwide problem partly because of difficulties with vaccination of young infants. New vaccine strategies need to be safe and to provide sustained protective immunity. We have developed Sindbis virus replicon particles that express the measles virus (MV) hemagglutinin (SIN-H) or fusion (SIN-F) proteins. in mice, SIN-H induced high-titered, dose-dependent, MV-neutralizing antibody after a single vaccination. SIN-F, or SIN-H and SIN-F combined, induced somewhat lower responses. To assess protective efficacy, juvenile macaques were vaccinated with a single dose of 106 or 108 SIN-H particles and infant macaques with two doses of 108 particles. A dose of 108 particles induced sustained levels of high-titered, MV-neutralizing antibody and IFN-gamma-producing memory T cells, and most monkeys were protected from rash when challenged with wild-type MV 18 months later. After challenge, there was a biphasic appearance of H- and F-specific IFN-rsecreting CD4(+) and CD8(+) T cells in vaccinated monkeys, with peaks approximate to 1 and 3-4 months after challenge. Viremia was cleared within 14 days, but MV RNA was detectable for 4-5 months. These studies suggest that complete clearance of MV after infection is a prolonged, phased, and complex process influenced by prior vaccination.
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