Current research for a vaccine against Lassa hemorrhagic fever virus

Abstract

Lassa virus (LASV) is a rodent-borne arenavirus endemic to several West African countries that causes Lassa fever (LF). LF is typically mild but it can cause severe disease characterized by hemorrhagic fever and multi-organ failure. A current outbreak of LASV in Nigeria has seen greater than 300 cases with a case fatality rate of 22%. Currently, there are limited treatment options and no vaccine candidates are approved to prevent LASV infection. The Coalition for Epidemic Preparedness Innovations has identified LASV as an emerging pathogen of high consequence and this has resulted in a push for several preclinical vaccine candidates to be advanced toward clinical trials. Here, we discuss several important aspects of LASV infection including immunobiology, immune evasion, and correlates of protection against LF, which have been identified through animal models and human infections. In addition, we discuss several vaccine candidates that have shown efficacy in animal models that could be advanced toward clinical trials. The increased fatality rate seen in the recent LASV outbreak in Nigeria highlights the importance of developing effective treatment and prevention strategies against LF. The spike in LASV cases seen in West Africa has the potential for increased mortality and human-to-human transmission, making the development and testing of effective vaccines for LASV critical.

Keywords: Lassa fever; Lassa virus; pathogenesis; prevention; therapeutics; vaccine.

Figure 1

Lassa virus geographical distribution and virus structure. Notes: Lassa virus has caused numerous outbreaks and is endemic to Nigeria, Guinea, Sierra Leone, and Liberia (red). There is also strong evidence of Lassa virus infections (beige) throughout much of West Africa (WHO Lassa Report, 201866). The Lassa virus structure and genome are also depicted. Abbreviations: RNA, ribonucleic acid; UTR, Untranslated Region; WHO, World Health Organization.

Figure 2

Disease course of Lassa virus infection and efficacy of various preventative strategies. Notes: The timeline of various aspects of disease course during Lassa virus infection in the most commonly used animal models and in humans (A), and the timeline of administration of various preventative strategies against Lassa virus infection (B). Each of the vaccine strategies listed has shown protective efficacy in guinea pigs and/or NHPs when administered at the day listed relative to infection. *Following symptom onset. Abbreviations: NHPs, non-human primates; Rib, ribavirin; Fav, favipiravir; VSV-LASV, vesicular stomatitis virus-Lassa virus.