1. ¹Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA
2. ²Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, USA
3. ³Bioject, Portland, Oregon, USA
4. ⁴Centers for Disease Control and Prevention, Atlanta, Georgia, USA
5. ⁵Bloomberg School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland, USA
6. ⁶Department of Medicine, Tropical Diseases Center, McGill University, Montreal, Quebec, Canada
7. ⁷GlaxoSmithKline Biologicals North America, Laval, Quebec, Canada
8. ⁸Novartis Vaccines and Diagnostics, Emeryville, California, USA
9. ⁹Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA

Correspondence: MF Pasetti, (mpasetti@medicine.umaryland.edu)

Received 19 July 2007; Accepted 10 September 2007; Published online 31 October 2007.

Abstract

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.