Migraine is a common episodic neurological disorder, typically presenting with recurrent attacks of severe headache and autonomic dysfunction. Apart from rare monogenic subtypes, no genetic or molecular markers for migraine have been convincingly established. We identified the minor allele of rs1835740 on chromosome 8q22.1 to be associated with migraine (p=5.12 × 10−9, OR 1.23 [1.150-1.324]) in a genome-wide association study of 2,748 migraineurs from three European headache clinics and 10,747 population-matched controls. The association was replicated in 3,202 cases and 40,062 controls for an overall meta-analysis p-value of 1.60 × 10−11 (OR 1.18 [1.127 – 1.244]). rs1835740 is located between the astrocyte elevated gene 1 (MTDH/AEG-1) and plasma glutamate carboxypeptidase (PGCP). In an expression quantitative trait study in lymphoblastoid cell lines transcript levels of the MTDH/AEG-1 were found to have a significant correlation to rs1835740. Our data establish rs1835740 as the first genetic risk factor for migraine.

Lassa fever (LF), caused by Lassa virus (LASV), is a viral hemorrhagic fever for which no approved vaccine or potent antiviral treatment is available. LF is a WHO priority disease and, together with rabies, a major health burden in West Africa. Here we present the development and characterization of an inactivated recombinant LASV and rabies vaccine candidate (LASSARAB) that expresses a codon-optimized LASV glycoprotein (coGPC) and is adjuvanted by a TLR-4 agonist (GLA-SE). LASSARAB elicits lasting humoral response against LASV and RABV in both mouse and guinea pig models, and it protects both guinea pigs and mice against LF. We also demonstrate a previously unexplored role for non-neutralizing LASV GPC-specific antibodies as a major mechanism of protection by LASSARAB against LF through antibody-dependent cellular functions. Overall, these findings demonstrate an effective inactivated LF vaccine and elucidate a novel humoral correlate of protection for LF.

The 2013-2016 West African Ebola virus (EBOV) disease outbreak was the largest filovirus outbreak to date. Over 28 000 suspected, probable, or confirmed cases have been reported, with a 53% case-fatality rate. The magnitude and international impact of this EBOV outbreak has highlighted the urgent need for a safe and efficient EBOV vaccine. To this end, we demonstrate the immunogenicity and protective efficacy of FILORAB1, a recombinant, bivalent, inactivated rabies virus-based EBOV vaccine, in rhesus and cynomolgus monkeys. Our results demonstrate that the use of the synthetic Toll-like receptor 4 agonist glucopyranosyl lipid A in stable emulsion (GLA-SE) as an adjuvant increased the efficacy of FILORAB1 to 100% protection against lethal EBOV challenge, with no to mild clinical signs of disease. Furthermore, all vaccinated subjects developed protective anti-rabies virus antibody titers. Taken together, these results support further development of FILORAB1/GLA-SE as an effective preexposure EBOV vaccine.