Vaccine platforms to control Lassa fever

Lukashevich, Igor S.; Pushko, Peter

doi:10.1080/14760584.2016.1184575

Cited by 38 publications

(30 citation statements)

References 133 publications

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“…Subsequently, the efficacy of YF17D/LASV-GPC prime-boost vaccination was assessed in marmosets after lethal challenge with Josiah strain LASV. The immunisation regimen was not protective and all vaccinated animals died with clinical signs of Lassa fever (Lukashevich IS, unpublished data, reviewed in [81]). These data further support the assertion that responses to immunisation in guinea pig models of infection may not fully predict those in NHPs.…”

Section: Yellow Fever 17d Virus-vectored Vaccinesmentioning

confidence: 99%

Vaccine platforms for the prevention of Lassa fever

2019

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A B S T R A C TLassa fever is an acute viral haemorrhagic illness caused by Lassa virus (LASV), which is endemic throughout much of West Africa. The virus primarily circulates in the Mastomys natalensis reservoir and is transmitted to humans through contact with infectious rodents or their secretions; human-to-human transmission is documented as well. With the exception of Dengue fever, LASV has the highest human impact of any haemorrhagic fever virus. On-going outbreaks in Nigeria have resulted in unprecedented mortality. Consequently, the World Health Organization (WHO) has listed LASV as a high priority pathogen for the development of treatments and prophylactics. Currently, there are no licensed vaccines to protect against LASV infection. Although numerous candidates have demonstrated efficacy in animal models, to date, only a single candidate has advanced to clinical trials. Lassa fever vaccine development efforts have been hindered by the high cost of biocontainment requirements, the absence of established correlates of protection, and uncertainty regarding the extent to which animal models are predictive of vaccine efficacy in humans. This review briefly discusses the epidemiology and biology of LASV infection and highlights recent progress in vaccine development.

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Section: Yellow Fever 17d Virus-vectored Vaccinesmentioning

confidence: 99%

Vaccine platforms for the prevention of Lassa fever

2019

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“…Due to the immunosuppressive nature of vaccinia virus, further development of this vaccine platform was abandoned out of safety concerns, particularly in immunocompromised individuals (51). The yellow fever virus 17D (YF17D) backbone, which encodes the LASV glycoprotein or glycoprotein subunits, has also been developed as a LASV vaccine, although its immunogenicity is poor and it lacks efficacy in nonhuman primates (50,57,58). Likewise, inactivated LASV failed to protect nonhuman primates from fatal Lassa fever (59).…”

Section: Alternatives To Vesicular Stomatitis Virus-based Lassa Fevermentioning

confidence: 99%

“…In addition to VSV-LASV, the most advanced LASV vaccine candidate is based on a reassortant between LASV and the reportedly non-pathogenic Mopeia virus (MOPV) (50,51). Clone ML29 possesses genetic material from both MOPV and LASVincluding the nucleoprotein and glycoprotein genes from the latter-and includes several additional point mutations that are thought to further attenuate the virus (66,70,71).…”

Section: Alternatives To Vesicular Stomatitis Virus-based Lassa Fevermentioning

confidence: 99%

Pre-clinical development of a vaccine against Lassa fever

Banadyga¹,

Stein²,

Qiu³

et al. 2018

CCDR

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Lassa virus (LASV) is a persistent global health threat that causes about half a million cases of Lassa fever each year in Western Africa. Although most cases are mild, the disease can cause significant morbidity and results in as many as 5,000 deaths per year. Since 2015, Nigeria has been experiencing a severe and extended outbreak of Lassa fever, raising concerns that it could spill over into other countries and reach a magnitude similar to the West African Ebola outbreak of 2013-2016. Despite the burden that Lassa fever places on public health, both in Africa and around the world, there are still no clinically-approved therapeutics or vaccines to treat or prevent it. Nevertheless, a number of promising candidate vaccines have been developed over the last several years, and there is a growing political and social determination to drive at least one of these candidates towards licensure. This paper describes a LASV vaccine candidate that is being developed at Canada's National Microbiology Laboratory. Based on the same live attenuated vesicular stomatitis virus (VSV) vaccine platform that was used to produce the successful Ebola virus vaccine, the VSV-based LASV vaccine has been shown to elicit a potent and protective immune response against LASV. The vaccine shows 100% protection in the "gold-standard" nonhuman primate model of Lassa fever, inducing both humoral and cellular immune responses. Moreover, studies have shown that a single vaccination may offer universal protection against numerous different strains of the virus, and additional studies have shown that immunization with the VSV platform appears to be unaffected by pre-existing immunity to VSV. The next step in the development of the VSV-based LASV vaccine is phase I human clinical trials to assess vaccine safety and dosage.

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“…Étant donné la nature immunodépressive du virus de la vaccine, cette base vaccinale a été abandonnée en cours de mise au point pour des raisons d'innocuité, surtout chez les individus immunodéprimés (51). La souche 17D du virus de la fièvre jaune (YF17D), codant pour la glycoprotéine ou des sous-unités de la glycoprotéine du virus Lassa, a aussi été utilisée dans un vaccin contre le virus Lassa, quoique son immunogénicité soit faible et peu efficace chez les primates non humains (50,57,58). De même, le virus Lassa inactivé n'a pas conféré de protection contre une fièvre de Lassa mortelle chez les primates non humains (59).…”

Section: Introductionunclassified

“…En plus du vaccin VSV-LASV, le candidat-vaccin contre le virus Lassa le plus perfectionné utilise comme base un virus réassorti à partir du virus Lassa et du virus Mopeia (qui serait non pathogène)(50,51). Le clone ML29 possède du matériel génétique provenant du virus Mopeia et du virus Lassanotamment les gènes codant pour la nucléoprotéine et la COMMENTAIRE glycoprotéine de ce dernier -et comporte plusieurs autres mutations ponctuelles qui atténueraient davantage le virus (66,70,71).…”

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