Abstract
BackgroundRecent importation of Lassa fever into Germany, the Netherlands, the United Kingdom, and the United States by travelers on commercial airlines from Africa underscores the public health challenge of emerging viruses. Currently, there are no licensed vaccines for Lassa fever, and no experimental vaccine has completely protected nonhuman primates against a lethal challenge.Methods and FindingsWe developed a replication-competent vaccine against Lassa virus based on attenuated recombinant vesicular stomatitis virus vectors expressing the Lassa viral glycoprotein. A single intramuscular vaccination of the Lassa vaccine elicited a protective immune response in nonhuman primates against a lethal Lassa virus challenge. Vaccine shedding was not detected in the monkeys, and none of the animals developed fever or other symptoms of illness associated with vaccination. The Lassa vaccine induced strong humoral and cellular immune responses in the four vaccinated and challenged monkeys. Despite a transient Lassa viremia in vaccinated animals 7 d after challenge, the vaccinated animals showed no evidence of clinical disease. In contrast, the two control animals developed severe symptoms including rashes, facial edema, and elevated liver enzymes, and ultimately succumbed to the Lassa infection.ConclusionOur data suggest that the Lassa vaccine candidate based on recombinant vesicular stomatitis virus is safe and highly efficacious in a relevant animal model that faithfully reproduces human disease.
Highlights
Among the viruses causing severe hemorrhagic fever in Africa, Lassa fever is a significant public health problem in Nigeria, Liberia, Sierra Leone, and the Republic of Guinea
We developed a replication-competent vaccine against Lassa virus based on attenuated recombinant vesicular stomatitis virus vectors expressing the Lassa viral glycoprotein
Our data suggest that the Lassa vaccine candidate based on recombinant vesicular stomatitis virus is safe and highly efficacious in a relevant animal model that faithfully reproduces human disease
Summary
Lassa fever is a disease caused by a virus that is often spread by rodents. The disease is common in parts of West Africa where it causes a significant amount of death and disability among the population. The researchers developed a vaccine using a virus called vesicular stomatitis virus as the harmless component (known as the carrier). They inserted some genetic material from the harmful Lassa virus. In their study, they gave four macaque monkeys one shot of this combination vaccine and two others shots of the ‘‘empty’’ carrier (i.e., just the harmless component). Issues that need to be resolved before the vaccine can be tested in humans include the safety of the vesicular stomatitis carrier virus, how long the vaccine protects after the shot, and whether it is active against different strains of the Lassa virus (there are at least four strains, each with slightly different genetic material). The US CDC Special Pathogens Branch Web site: http://www.cdc.gov/ ncidod/dvrd/spb/ The WHO fact sheet on Lassa Fever (from 2000): http://www.who.int/ mediacentre/factsheets/fs179/en/
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