Background: Despite the availability of a safe and effective vaccine for over four decades, measles remains one of the most common infectious disease killers of children in the world. Mucosal administration of currently licensed measles vaccine has been proposed to address issues of needle safety and improve vaccine uptake.

Methods: Healthy adult volunteers were randomized to receive live-attenuated monovalent measles virus vaccine (Moraten Berna) via the standard subcutaneous (SQ) or the experimental intranasal (IN) route in a randomized, double-masked fashion. Safety, reactogenicity, immunogenicity, and shedding were assessed.

Results: Safety, reactogenicity, and viral shedding were not significantly different in the two study groups. Immunogenicity was markedly lower in the group of volunteers that received vaccine via the IN route. Plaque reduction neutralization (PRN) geometric mean titers (GMT) were 125 (95% confidence interval [CI] 68-228) milli International Units per milliliter (mIU/mL) on day 28 in recipients of IN vaccine versus 645 (95% CI 468-889) mIU/mL in recipients of vaccine SQ; p< 0.001 by Mann-Whitney Rank Sum. 50% of measles non-immune individuals mounted titers above the protective threshold of PRN 200 mIU/mL after IN administration versus 100% of volunteers who received the vaccine SQ.

Conclusion: Intranasal administration of live-attenuated measles vaccine was safe and well tolerated, but failed to mount significant immune responses when compared to subcutaneous administration. It is possible that higher doses or smaller particle size are necessary for successful intranasal measles vaccination and boosting.

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