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Japanese encephalitis virus (JEV) is the leading cause of human encephalitis in Asia. JEV is a vector-borne disease, mainly transmitted by Culex mosquitoes, with Ardeidae birds as maintenance hosts and pigs as amplifying hosts. Other vertebrate animal hosts have been suggested to play a role in the epidemiology of JEV. This scoping review followed PRISMA guidelines to identify species in which evidence of naturally occurring JEV infection was detected in vertebrates other than ardeid birds, pigs and people. Following systematic searches, 4372 records were screened, and data were extracted from 62 eligible studies. Direct evidence (virus, viral antigen or viral RNA) of JEV infection was identified in a variety of mammals and birds (not always identified to the species level), including bats, passerine birds (family Turdidae), livestock (cattle [Bos taurus] and a goat [Capra hircus]), carnivores (two meerkats [Suricata suricatta]), and one horse (Equus caballus). Bat families included Pteropodidae, Vespertilionidae, Rhinolophidae, Miniopteridae, Hipposideridae. Indirect evidence (antibodies) was identified in several mammalian and avian orders, as well as reported in two reptile species. However, a major limitation of the evidence of JEV infection identified in this review was diagnostic test accuracy, particularly for serological testing. Studies generally did not report diagnostic sensitivity or specificity which is critical given the potential for cross-reactivity in orthoflavivirus detection. We hypothesise that bats and passerine birds could play an underappreciated role in JEV epidemiology; however, development of diagnostic tests to differentiate JEV from other orthoflaviviruses will be essential for effective surveillance in these, as well as the companion and livestock species that could be used to evaluate JEV control measures in currently endemic regions. Author summary: Japanese encephalitis virus (JEV) is the leading cause of encephalitis in Asia and the Western Pacific, with estimated 100,000 cases in people (mainly children) annually. Up to one third of cases result in death, and of those who survive, half can suffer ongoing neurological problems. Japanese encephalitis virus circulation is complex. It is transmitted via mosquitoes between hosts. Although well-known key hosts include pigs and water birds, our review showed that there are others that should be considered in surveillance programs such as bats and perching birds. We also found that detection is challenging because diagnostic tests cross-react with other viruses. Both improved understanding of hosts and better diagnostic tests are needed to develop surveillance systems to reduce JEV incidence in people. [ABSTRACT FROM AUTHOR]

Live-attenuated influenza vaccines (LAIV) offer advantages over the commonly used inactivated split influenza vaccines. However, finding the optimal balance between sufficient attenuation and immunogenicity has remained a challenge. We recently developed an alternative LAIV based on the 2009 pandemic H1N1 virus with a truncated NS1 protein and lacking PA-X protein expression (NS1(1–126)-ΔPAX). This virus showed a blunted replication and elicited a strong innate immune response. In the present study, we evaluated the efficacy of this vaccine candidate in the porcine animal model as a pertinent in vivo system. Immunization of pigs via the nasal route with the novel NS1(1–126)-ΔPAX LAIV did not cause disease and elicited a strong mucosal immune response that completely blocked replication of the homologous challenge virus in the respiratory tract. However, we observed prolonged shedding of our vaccine candidate from the upper respiratory tract. To improve LAIV safety, we developed a novel prime/boost vaccination strategy combining primary intramuscular immunization with a haemagglutinin-encoding propagation-defective vesicular stomatitis virus (VSV) replicon, followed by a secondary immunization with the NS1(1–126)-ΔPAX LAIV via the nasal route. This two-step immunization procedure significantly reduced LAIV shedding, increased the production of specific serum IgG, neutralizing antibodies, and Th1 memory cells, and resulted in sterilizing immunity against homologous virus challenge. In conclusion, our novel intramuscular prime/intranasal boost regimen interferes with virus shedding and transmission, a feature that will help combat influenza epidemics and pandemics. Author summary: Nasally administered live-attenuated influenza vaccines induce a mucosal immune response that can effectively prevent primary infection and virus shedding. However, the development of alternative live vaccine strategies must consider the balance between eliciting a robust immune response and reducing the virulence of the vaccine candidate. To address this problem, we have developed a novel prime/boost vaccination strategy consisting of an initial intramuscular immunization with a propagation-defective RNA virus vector and subsequent nasal immunization with a modified attenuated influenza virus that has lost its ability to counteract the host innate immune response. Using the porcine model, we demonstrate that this novel strategy is capable of eliciting a robust immune response both systemically and at mucosal surfaces. Importantly, intranasal infection with homologous challenge virus remained undetectable in vaccinated animals. In conclusion, our innovative vaccination regimen represents a promising strategy to control influenza disease and virus spread in both humans and livestock. [ABSTRACT FROM AUTHOR]

The 2015–17 Zika virus (ZIKV) epidemic in the Americas subsided faster than expected and evolving population immunity was postulated to be the main reason. Herd immunization is suggested to occur around 60–70% seroprevalence, depending on demographic density and climate suitability. However, herd immunity was only documented for a few cities in South America, meaning a substantial portion of the population might still be vulnerable to a future Zika virus outbreak. The aim of our study was to determine the vulnerability of populations to ZIKV by comparing the environmental suitability of ZIKV transmission to the observed seroprevalence, based on published studies. Using a systematic search, we collected seroprevalence and geospatial data for 119 unique locations from 37 studies. Extracting the environmental suitability at each location and converting to a hypothetical expected seroprevalence, we were able to determine the discrepancy between observed and expected. This discrepancy is an indicator of vulnerability and divided into three categories: high risk, low risk, and very low risk. The vulnerability was used to evaluate the level of risk that each location still has for a ZIKV outbreak to occur. Of the 119 unique locations, 69 locations (58%) fell within the high risk category, 47 locations (39%) fell within the low risk category, and 3 locations (3%) fell within the very low risk category. The considerable heterogeneity between environmental suitability and seroprevalence potentially leaves a large population vulnerable to future infection. Vulnerability seems to be especially pronounced at the fringes of the environmental suitability for ZIKV (e.g. Sao Paulo, Brazil). The discrepancies between observed and expected seroprevalence raise the question: "why did the ZIKV epidemic stop with large populations unaffected?". This lack of understanding also highlights that future ZIKV outbreaks currently cannot be predicted with confidence. Author summary: After the ZIKV epidemic in the Americas, it remains unclear if and when a resurgence of the ZIKV could occur. We used publicly available data on environmental suitability of transmission as well as seroprevalence data to estimate future vulnerability to ZIKV outbreaks. Our results show a considerable discrepancy between the observed seroprevalence, from past exposure to the virus on one hand, and the environmental suitability, which raised the question why the epidemic subsided before reaching the expected herd immunization threshold in many locations. This lack of understanding also highlights that future ZIKV outbreaks currently cannot be predicted with confidence. Although we cannot provide an answer to the question why the epidemic subsided when it did, we present a better quantification and geospatial mapping of the potential vulnerability to future outbreaks, which will be crucial for decision makers to prepare for future outbreaks. [ABSTRACT FROM AUTHOR]