The search for animal models for Lassa fever vaccine development

Lukashevich, Igor S.

doi:10.1586/erv.12.139

Cited by 42 publications

(36 citation statements)

References 126 publications

(162 reference statements)

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“…During arenavirus infection, the initial innate immune response and the activation of the type I IFN system are essential to prime subsequent cellular and adaptive immune responses to eventually overcome and clear the infection (34)(35)(36)(37). In adult mice infected with LCMV, an IFN burst was observed from 6 to 48 h postinfection (38)(39)(40).…”

Section: Cellular Immune Responses Upon Ifn Induction During Arenavirmentioning

confidence: 99%

Inhibition of Innate Immune Responses Is Key to Pathogenesis by Arenaviruses

Meyer

2016

J Virol

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Mammalian arenaviruses are zoonotic viruses that cause asymptomatic, persistent infections in their rodent hosts but can lead to severe and lethal hemorrhagic fever with bleeding and multiorgan failure in human patients. Lassa virus (LASV), for example, is endemic in several West African countries, where it is responsible for an estimated 500,000 infections and 5,000 deaths annually. There are currently no FDA-licensed therapeutics or vaccines available to combat arenavirus infection. A hallmark of arenavirus infection (e.g., LASV) is general immunosuppression that contributes to high viremia. Here, we discuss the early host immune responses to arenavirus infection and the recently discovered molecular mechanisms that enable pathogenic viruses to suppress host immune recognition and to contribute to the high degree of virulence. We also directly compare the innate immune evasion mechanisms between arenaviruses and other hemorrhagic fever-causing viruses, such as Ebola, Marburg, Dengue, and hantaviruses. A better understanding of the immunosuppression and immune evasion strategies of these deadly viruses may guide the development of novel preventative and therapeutic options.

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Section: Cellular Immune Responses Upon Ifn Induction During Arenavirmentioning

confidence: 99%

Inhibition of Innate Immune Responses Is Key to Pathogenesis by Arenaviruses

Meyer

2016

J Virol

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“…Recently documented evidence of LASV reassortment in vivo [10] raises the concern that in endemic areas vaccination with an RC vaccine will affect the natural pattern of the disease and enhance pathogenicity due to reassortment (and/or recombination) between LASV and a vaccine strain. To address this concern, strain 13 guinea pigs (the most sensitive animal model, LD 50 < 1 PFU) [114] were inoculated with ML29 and immediately after that challenged with either homologous LASVJos/SL or with distantly-related LASV-803213/NIG from clade II. In homologous group, all animals were fully protected against fatal disease independently on the challenged dose.…”

Section: Reassortant Vaccine Platform Mopv/lasv (Clone Ml29)mentioning

confidence: 99%

Vaccine platforms to control Lassa fever

Lukashevich

Pushko

2016

Expert Review of Vaccines

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LASV vaccine development is hampered by high cost of biocontainment requirement, the absence of appropriate small animal models, genetic diversity of LASV species, and by high HIV-1 prevalence in LASV endemic areas. Over the past 15 years several vaccine platforms have been developed. Natural history of LASV and pathogenesis of the disease provide strong justification for replication-competent (RC) vaccine as one of the most feasible approaches to control LF. Development of LASV vaccine candidates based on reassortant, recombinant, and alphavirus replicon technologies is covered in this review. Expert commentary: Two lead RC vaccine candidates, reassortant ML29 and recombinant VSV/LASV, have been successfully tested in non-human primates and have been recommended by international vaccine experts for rapid clinical development. Both platforms have powerful molecular tools to further secure safety, improve immunogenicity, and cross-protection. These platforms are well positioned to design multivalent vaccines to protect against all LASV strains citculatrd in West Africa. The regulatory pathway of Candid #1, the first live-attenuated arenaviral vaccine against Argentine hemorrhagic, will be a reasonable guideline for LASV vaccine efficacy trials.

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“…Lymphopenia has been identified in LASV-infected cynomolgus monkeys [97,98]; meanwhile, depletion or reduction of T cells and B cells has also been found in livers and spleens of LASV-infected marmosets [99]. Thus, lethal LASV infection in non-human primates seems to be accompanied with weak innate and cellular immune responses and uncontrolled viral replication, which are similar to that usually found in patients [24,[97][98][99].…”

Section: Innate Immune Response To Ow Arenavirusesmentioning

confidence: 76%

Innate Immune Response to Arenaviral Infection: A Focus on the Highly Pathogenic New World Hemorrhagic Arenaviruses

Koma

Huang

Kolokoltsova

et al. 2013

Journal of Molecular Biology

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Arenaviruses are enveloped, negative-stranded RNA viruses that belong to the family Arenaviridae. This diverse family can be further classified into OW (Old World) and NW (New World) arenaviruses based on their antigenicity, phylogeny, and geographical distribution. Many of the NW arenaviruses are highly pathogenic viruses that cause systemic human infections characterized by hemorrhagic fever and/or neurological manifestations, constituting public health problems in their endemic regions. NW arenavirus infection induces a variety of host innate immune responses, which could contribute to the viral pathogenesis and/or influence the final outcome of virus infection in vitro as well as in vivo. On the other hand, NW arenaviruses have also developed several strategies to counteract the host innate immune response. We will review current knowledge regarding the interplay between the host innate immune response and NW arenavirus infection in vitro and in vivo, with emphasis on viral-encoded proteins and their effect on the type I interferon response.

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The search for animal models for Lassa fever vaccine development

Cited by 42 publications

References 126 publications

Inhibition of Innate Immune Responses Is Key to Pathogenesis by Arenaviruses

Inhibition of Innate Immune Responses Is Key to Pathogenesis by Arenaviruses

Vaccine platforms to control Lassa fever

Innate Immune Response to Arenaviral Infection: A Focus on the Highly Pathogenic New World Hemorrhagic Arenaviruses

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