id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-268677-ytxrrslz	Züst, Roland	Rational Design of a Live Attenuated Dengue Vaccine: 2′-O-Methyltransferase Mutants Are Highly Attenuated and Immunogenic in Mice and Macaques	2013-08-01		.txt	text/plain	7936	436	55	Here we demonstrate that DENV strains bearing a mutation in the catalytic site of the 29-O-MTase replicated to high titres in cell culture whereas these mutant viruses were highly attenuated in mice and rhesus monkeys. Mice and monkeys infected with the mutant virus developed an immune response that fully protected them from a challenge with wild-type virus. These data suggest that vaccination with the E216A/E217A mutants does not cause ADE during heterologous challenge even though lower neutralizing Ab titers are generated by the mutant strains compared to the wild-type virus. To assess the safety (viremia profile) and efficacy (neutralizing antibody response and protection against challenge) of the 29-O-MTase mutant DENV vaccine approach in an immunologically competent host, three groups of Rhesus monkeys (RM) were immunized with different doses of E217A. These data demonstrate that live, attenuated DENV MTase mutant virus, even when administrated at low dose (1610 3 PFU), can induce protective immunity in non-human primates.	./cache/cord-268677-ytxrrslz.txt	./txt/cord-268677-ytxrrslz.txt