Measles DNA vaccine priming for young infants

Despite the overall progress achieved with mass immunization campaigns in sub-Saharan Africa, measles mortality in young children remains a significant public health problem. Investigators at the Center for Vaccine Development (CVD) developed two Sindbis replicon-based measles DNA vaccine candidates encoding the measles virus (MV) hemagglutinin (H) or H and fusion (F) proteins to specifically target infants who are too young to receive the currently licensed measles vaccines. The Sindbis DNA replicons were well tolerated and highly immunogenic, eliciting plaque reduction neutralizing antibodies and measles-specific IFN-γ secreting T cells when administered to cotton rats, newborn and adult mice, and to juvenile and very young infant rhesus monkeys. A heterologous prime-boost regimen consisting of parenteral priming with DNA vaccine encoding H (pMSIN-H) and boosting with aerosolized attenuated MV vaccine was well tolerated by very young infant rhesus macaque monkeys and protected against viremia following respiratory challenge with wild type MV. A randomized, double-blind, placebo-controlled, Phase 1 clinical trial was conducted to evaluate the safety of these DNA vaccines in healthy adults living in the U.S.A. Three dosage levels of ∼200, 400 and 800 μg of each DNA vaccine administered in a 2-dose regimen were found to be safe and well tolerated. Among the various candidate DNA vaccine strategies for young infants, this is the most advanced, having been tested in a Phase 1 clinical study. If successful, the proposed strategy would allow to prevent the “window of vulnerability” that otherwise opens at ∼16 weeks of age as maternal antibodies wane.