Vaccine platforms to control Lassa fever.

INTRODUCTION: Lassa virus (LASV), the most prominent human pathogen of the Arenaviridae, is transmitted to humans from infected rodents and can cause Lassa Fever (LF). The sizeable disease burden in West Africa, numerous imported LF cases worldwide, and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. There are no licensed LASV vaccines and the antiviral treatment is limited to an off-label use of ribavirin that is only partially effective. AREAS COVERED: 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.

Hemagglutinin amino acids related to receptor specificity could affect the protection efficacy of H5N1 and H7N9 avian influenza virus vaccines in mice.

The continuous and sporadic human transmission of highly pathogenic avian H5N1 and H7N9 influenza viruses illustrates the urgent need for efficacious vaccines. However, all tested vaccines for the H5N1 and H7N9 viruses appear to be poorly immunogenic in mammals. In this study, a series of vaccines was produced using reverse genetic techniques that possess HA and NA genes from the H5N1 virus in the genetic background of the high-yield strain A/PR/8/34 (H1N1). Meanwhile, a group of H7N9 VLP vaccines that contain HA from H7N9 and NA and M1 from A/PR/8/34 (H1N1) was also produced. The HA amino acids of both the H5N1 and H7N9 vaccines differed at residues 226 and 228, both of which are critical for receptor specificity for an avian or mammalian host. Mice received two doses (3µg of HA each) of each vaccine and were challenged with lethal doses of wild type H5N1 or H7N9 viruses. The results showed that a recombinant H5N1 vaccine in which the HA amino acid G228 (avian specificity) was converted to S228 (mammalian specificity) resulted in higher HI titers, a lower viral titer in the lungs, and 100% protection in mice. However, a H7N9 VLP vaccine that contains L226 (mammalian specificity) and G228 (avian specificity) in HA showed better immunogenicity and protection efficacy in mice than VLP containing HA with either L226+S228 or Q226+S228. This observation indicated that specific HA residues could enhance a vaccine's protection efficacy and HA glycoproteins with both avian-type and human-type receptor specificities may produce better pandemic influenza vaccines for humans.