Influence of Lipid Composition of Cationic Liposomes 2X3-DOPE on mRNA Delivery into Eukaryotic Cells.

The design of cationic liposomes for efficient mRNA delivery can significantly improve mRNA-based therapies. Lipoplexes based on polycationic lipid 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2X3) and helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) were formulated in different molar ratios (1:1, 1:2, 1:3) to efficiently deliver model mRNAs to BHK-21 and A549. The objective of this study was to examine the effect of 2X3-DOPE composition as well as lipid-to-mRNA ratio (amino-to-phosphate group ratio, N/P) on mRNA transfection.

The Key Roles of Interferon Lambda in Human Molecular Defense against Respiratory Viral Infections.

Interferons (IFN) are crucial for the innate immune response. Slightly more than two decades ago, a new type of IFN was discovered: the lambda IFN (type III IFN). Like other IFN, the type III IFN display antiviral activity against a wide variety of infections, they induce expression of antiviral, interferon-stimulated genes (, , ), and they have immuno-modulatory activities that shape adaptive immune responses.

An attenuated Lassa vaccine in SIV-infected rhesus macaques does not persist or cause arenavirus disease but does elicit Lassa virus-specific immunity.

Background: Lassa hemorrhagic fever (LHF) is a rodent-borne viral disease that can be fatal for human beings. In this study, an attenuated Lassa vaccine candidate, ML29, was tested in SIV-infected rhesus macaques for its ability to elicit immune responses without instigating signs pathognomonic for arenavirus disease. ML29 is a reassortant between Lassa and Mopeia viruses that causes a transient infection in non-human primates and confers sterilizing protection from lethal Lassa viral challenge.

Lymphocytic choriomeningitis virus (LCMV) infection of macaques: a model for Lassa fever.

Arenaviruses such as Lassa fever virus (LASV) and lymphocytic choriomeningitis virus (LCMV) are benign in their natural reservoir hosts, and can occasionally cause severe viral hemorrhagic fever (VHF) in non-human primates and in human beings. LCMV is considerably more benign for human beings than Lassa virus, however certain strains, like the LCMV-WE strain, can cause severe disease when the virus is delivered as a high-dose inoculum. Here we describe a rhesus macaque model for Lassa fever that employs a virulent strain of LCMV.

Anti-HIV-1 activity of the neurokinin-1 receptor antagonist aprepitant and synergistic interactions with other antiretrovirals.

Objectives: Neurokinin-1 receptor (NK1R) antagonists interfere with binding of neuropeptide substance P to NK1R and exhibit novel anti-HIV-1 activities. Since NK1R antagonists effectively penetrate the blood-brain barrier to reduce the inflammatory response within the brain, we wished to evaluate their potential as anti-HIV-1 candidates for targeting HIV-1 infections of the central nervous system.

Design: A series of small molecule agents were evaluated for anti-NK1R and anti-HIV-1 activity using peripheral blood mononuclear cells (PBMCs).

A ML29 reassortant virus protects guinea pigs against a distantly related Nigerian strain of Lassa virus and can provide sterilizing immunity.

Lassa virus (LASV) is responsible for the deaths of thousands of people in West Africa annually. Genetic diversity among LASV strains is the highest among the Arenaviridae and represents a great challenge for vaccine development. Guinea pigs vaccinated with a ML29 reassortant vaccine experienced sterilizing immunity and complete protection when challenged on day 30 either with homologous virus or with the distantly related Nigerian isolate.

Molecular characterization of a reassortant virus derived from Lassa and Mopeia viruses.

In this article we describe two new complete genomic sequences of Old World Arenaviruses: the Mopeia (MOP) virus and the reassortant MOP/LAS virus, clone 29, or ML29. This reassortant has the large (L) RNA from MOP virus and the small (S) RNA from Lassa (LAS) virus, Josiah strain. Recent studies showed that the ML29 virus is not pathogenic for mice, guinea pigs, or macaques, can completely protect guinea pigs from Lassa virus, and elicit vigorous cell-mediated immunity in immunized monkeys (Lukashevich, I.

A recombinant Yellow Fever 17D vaccine expressing Lassa virus glycoproteins.

The Yellow Fever Vaccine 17D (YFV17D) has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) resulting in construction of YFV17D/LASV-GPC recombinant virus. The virus was replication-competent and processed the LASV-GPC in cell cultures. The recombinant replicated poorly in guinea pigs but still elicited specific antibodies against LASV and YFV17D antigens.

A live attenuated vaccine for Lassa fever made by reassortment of Lassa and Mopeia viruses.

Lassa virus (LASV) and Mopeia virus (MOPV) are closely related Old World arenaviruses that can exchange genomic segments (reassort) during coinfection. Clone ML29, selected from a library of MOPV/LASV (MOP/LAS) reassortants, encodes the major antigens (nucleocapsid and glycoprotein) of LASV and the RNA polymerase and zinc-binding protein of MOPV. Replication of ML29 was attenuated in guinea pigs and nonhuman primates.