Effective vaccine for Lassa fever

Lassa fever has been estimated to cause 5,000 deaths annually in West Afric a. Recently, war in the zone where Lassa fever is hyperendemic has severely impeded control and treatment. Vaccination is the most viable control meas ure. There is no correlation between antibody levels and outcome in human p atients, and inactivated vaccines produce high titers of antibodies to all viral proteins but do not prevent virus replication and death in nonhuman p rimates. Accordingly, we vaccinated 44 macaques with vaccinia virus-express ed Lassa virus structural proteins separately and in combination, with the object of inducing a predominantly TH1-type immune response, Following Lass a virus challenge, all unvaccinated animals died (DQ survival). Nine of 10 animals vaccinated with all proteins survived (90% survival). Although no a nimals that received full-length glycoprotein alone had a high titer of ant ibody, 17 of 19 survived challenge (88%). In contrast, all animals vaccinat ed with nucleoprotein developed high titers of antibody but 12 of 15 died ( 20% survival). All animals vaccinated with single glycoproteins, G1 or G2, died, but all those that received both single glycoproteins (GI plus G2) at separate sites survived, showing that both glycoproteins are independently important in protection. Neither group had demonstrable antibody levels pr ior to challenge. We demonstrate that in primates, immune responses to epit opes on both glycoproteins are required to protect against lethal challenge with Lassa virus without having untoward side effects and that this protec tion is likely to be primarily cell mediated. We show that an effective, sa fe vaccine against Lassa virus can and should be made and that its evaluati on for human populations is a matter of humanitarian priority.