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Heterologous Prime–Boost Strategy to Immunize Very Young Infants against Measles: Pre‐clinical Studies in Rhesus Macaques
Author(s) -
Pasetti M F,
ResendizAlbor A,
Ramirez K,
Stout R,
Papania M,
Adams R J,
Polack F P,
Ward B J,
Burt D,
Chabot S,
Ulmer J,
Barry E M,
Levine M M
Publication year - 2007
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100420
Subject(s) - measles , medicine , virology , viremia , immunology , vaccination , rubella , measles vaccine , dna vaccination , immunization , measles virus , virus , antibody
Infants in developing countries are at high risk of developing severe clinical measles if they become infected during the “window of vulnerability” (age 4–9 months), when declining maternal antibodies do not protect against wild virus, yet impede successful immunization by attenuated measles vaccine. We developed two Sindbis replicon‐based DNA vaccines expressing measles virus hemagglutinin and fusion protein with the goal of priming young infants to respond safely and effectively to subsequent boosting with attenuated measles vaccine. Intradermal prime with DNA vaccines by needle‐free injection followed by aerosol or parenteral boost with licensed measles vaccine was well tolerated by juvenile and young infant rhesus macaques, and protected against clinical measles and viremia on wild‐type virus challenge. A proteosome‐measles vaccine administered alone (three doses) or as a boost following DNA vaccine priming was also safe and protective. These promising results pave the way for clinical trials to assess this prime–boost strategy. Clinical Pharmacology & Therapeutics (2007) 82 , 672–685; doi: 10.1038/sj.clpt.6100420 ; published online 31 October 2007