Towards a human Lassa fever vaccine

Arenaviruses, such as Lassa fever, establish chronic infections in rodents, leading to incidental transmission to humans. Lassa fever is a clinically severe disease, yet the absence of second attacks implies life-long immunit y. The aim of this review is to consider whether such immunity could be pro vided by vaccines. The South American arenaviruses are controlled by neutra lising antibody and a clinical trial of live, attenuated vaccine for Argent inian haemorrhagic fever provided 84%. protection. In contrast, there is no evidence for protective humoral immunity against Old World arenaviruses wh ich are controlled by cell-mediated immune responses. Nevertheless, vaccina tion with Lassa glycoproteins can protect monkeys from disease, implying th at protection may be achievable, even though the immunological mechanisms a re distinct. Recombinant vaccinia viruses expressing various forms of Lassa glycoproteins can protect both guinea-pigs and primates, while additional protective responses can be mounted against nucleocapsid genes. However, va ccines based upon vaccinia constructs are no longer tenable for African pop ulations with a high seroprevalence of HIV infection. The scientific challe nge now remains to find alternative methods of delivering T-cell immunity a gainst glycoproteins from Lassa virus in ways which can overcome the local economic and political hurdles to vaccine development. Copyright (C) 2001 J ohn Wiley & Sons, Ltd.