Non-neutralizing antibodies elicited by recombinant Lassa-Rabies vaccine are critical for protection against Lassa fever

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.NIH grants R01 AI105204 to M.J.S., by the Jefferson Vaccine Center, and by the Fundação para a Ciência e Tecnologia (FCT) scholarship PD/BD/105847/2014 (to T.A.-M.). This work was also funded in part through the NIAID Division of Intramural Research and the NIAID Division of Clinical Research, Battelle Memorial Institute’s prime contract with the U.S. National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272200700016Iinfo:eu-repo/semantics/publishedVersio

Mapping the zoonotic niche of Lassa fever in Africa.

Lassa fever is a viral haemorrhagic illness responsible for disease outbreaks across West Africa. It is a zoonosis, with the primary reservoir species identified as the Natal multimammate mouse, Mastomys natalensis. The host is distributed across sub-Saharan Africa while the virus' range appears to be restricted to West Africa. The majority of infections result from interactions between the animal reservoir and human populations, although secondary transmission between humans can occur, particularly in hospital settings.Using a species distribution model, the locations of confirmed human and animal infections with Lassa virus (LASV) were used to generate a probabilistic surface of zoonotic transmission potential across sub-Saharan Africa.Our results predict that 37.7 million people in 14 countries, across much of West Africa, live in areas where conditions are suitable for zoonotic transmission of LASV. Four of these countries, where at-risk populations are predicted, have yet to report any cases of Lassa fever.These maps act as a spatial guide for future surveillance activities to better characterise the geographical distribution of the disease and understand the anthropological, virological and zoological interactions necessary for viral transmission. Combining this zoonotic niche map with detailed patient travel histories can aid differential diagnoses of febrile illnesses, enabling a more rapid response in providing care and reducing the risk of onward transmission

Forschungszentrum Karlsruhe Technik und Umwelt, Institut fuer Angewandte Informatik. Ergebnisbericht ueber Forschung und Entwicklung 1998

Available from TIB Hannover: ZA 5141(6239) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Birth cohort effects in neurological diseases: amyotrophic lateral sclerosis, Parkinson's disease and multiple sclerosis

Background: Generational differences in disease rates are the main subject of age-period-cohort (APC) analysis, which is mostly applied in cancer and suicide research. This study applied APC analysis to selected neurological diseases: amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and multiple sclerosis (MS). Methods: The analyses were based on Swiss mortality data. Age-stratified data has been available for MS, PD and ALS since 1901, 1921, and 1942, respectively. APC analysis was performed within the framework of logit models. Main effect models were extended by implementing nested effects, i.e. age effects nested in subperiods, in order to account for the fact that age profiles may change for reasons other than generational influences. Results: In preliminary analyses, APC analysis yielded noteworthy birth cohort effects in all three diseases. After implementing nested effects, the birth cohort effects disappeared in ALS, and smoothed out in PD, where they were greater for the generations born before the 1920s. In MS, the birth cohort effects remained stable, and exhibited a peak in cohorts born in the 1910s and 1920s. Conclusions: APC analysis yielded some evidence for birth cohort effects, i.e. predisposing risk factors that may change in historical terms, in MS and PD, but probably not in ALS