Development of a New Vaccine for the Prevention of Lassa Fever

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.

Requirement for CD4 T Cell Help in Maintenance of Memory CD8 T Cell Responses Is Epitope Dependent

“…3 expressing appropriate foreign Ags have been used to generate effective experimental vaccines protecting against infection or disease caused by multiple viral pathogens including an SIV-HIV hybrid causing AIDS in rhesus macaques (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). The VSV-based HIV vaccine developed in our laboratory has protected macaques from AIDS for up to 5 years postchallenge, but it does not generate sterilizing immunity (10).…”

The vesicular stomatitis virus-based Ebola virus vaccine: From concept to clinical trials

“…27 , 49 , 50 In addition, a dual VSV-based vector expressing the GPs of viruses from two different virus families was shown to protect against both viruses in an animal model with similar short time to protection and post-exposure efficacy as VSV-EBOV. 18 , 51 Now that the safety, efficacy, and feasibility of the VSV platform have been proven, it is time to finally license this platform, as has been recently done in Russia.…”

“…With the successful development of VSV-based vaccines against highly pathogenic viruses with geographically overlapping endemic areas, such as the VSV-EBOV and a VSV-based vaccine expressing the Lassa virus (LASV) glycoproteins (VSV-LASV), 27 , 28 the effect of pre-existing immunity to the vaccine vector on vaccine efficacy became a concern. To assess the effect of pre-existing immunity to the VSV vector, cynomolgus macaques previously vaccinated with VSV-LASV and challenged with LASV were vaccinated with VSV-EBOV 3 months after LASV challenge, and challenged with a lethal dose of EBOV.…”

Vaccines against viral hemorrhagic fevers: Non-human primate models

“…26,27 Squirrel monkeys (Saimiri sciureus) have also been experimentally infected with LASV. 28 Although high viral titers were noted, no significant gross lesions were obseved. Most importantly, microscopic examination of tissue from these infected animals had not evidence of hepatic lesions.…”