Summary For decades, arboviral diseases were considered to be only minor contributors to global mortality and disability. As a result, low priority was given to arbovirus research investment and ...related public health infrastructure. The past five decades, however, have seen an unprecedented emergence of epidemic arboviral diseases (notably dengue, chikungunya, yellow fever, and Zika virus disease) resulting from the triad of the modern world: urbanisation, globalisation, and international mobility. The public health emergency of Zika virus, and the threat of global spread of yellow fever, combined with the resurgence of dengue and chikungunya, constitute a wake-up call for governments, academia, funders, and WHO to strengthen programmes and enhance research in aedes-transmitted diseases. The common features of these diseases should stimulate similar research themes for diagnostics, vaccines, biological targets and immune responses, environmental determinants, and vector control measures. Combining interventions known to be effective against multiple arboviral diseases will offer the most cost-effective and sustainable strategy for disease reduction. New global alliances are needed to enable the combination of efforts and resources for more effective and timely solutions.
Japanese encephalitis virus is a mosquito-borne member of the
family. JEV is the leading cause of viral encephalitis in Asia and is characterized by encephalitis, high lethality, and neurological ...sequelae in survivors. The virus also causes severe disease in swine, which are an amplifying host in the transmission cycle, and in horses. US agricultural authorities have recently recognized the threat to the swine industry and initiated preparedness activities. Other mosquito-borne viruses exotic to the Western Hemisphere have been introduced and established in recent years, including West Nile, Zika, and chikungunya viruses, and JEV has recently invaded continental Australia for the first time. These events amply illustrate the potential threat of JEV to US health security. Susceptible indigenous mosquito vectors, birds, feral and domestic pigs, and possibly bats, constitute the receptive ecological ingredients for the spread of JEV in the US. Fortunately, unlike the other virus invaders mentioned above, an inactivated whole virus JE vaccine (IXIARO
) has been approved by the US Food and Drug Administration for human use in advance of a public health emergency, but there is no veterinary vaccine. This paper describes the risks and potential consequences of the introduction of JEV into the US, the need to integrate planning for such an event in public health policy, and the requirement for additional countermeasures, including antiviral drugs and an improved single dose vaccine that elicits durable immunity in both humans and livestock.
Highlights • Three frameworks for development and use of vaccines for control of zoonoses are provided. • Framework I vaccines target dead-end human and livestock hosts. • Framework II vaccines ...target infections of domesticated animals as a means of preventing spread to humans. • Framework III vaccines target wild animal reservoirs. • Collaboration of animal and human health disciplines (One Health) may accelerate new approaches to disease control.
The live, attenuated yellow fever (YF) 17D vaccine provides highly effective and durable immunity and is widely used for travelers to and residents of endemic areas of South America and Africa. ...Neurotropic and viscerotropic serious adverse events associated with these vaccines occur rarely, but YF 17D vaccine-associated viscerotropic disease (YEL-AVD) is notable for its lethality. There appear to be two distinct patterns of risk for YEL-AVD: the first in younger persons, particularly women, with defects in innate immunity, in whom the case-fatality rate is higher; and the second in elderly persons, particularly men with age-related immune senescence and a lower case-fatality rate. From 1990 to the present, the number of cases (n = 31) and deaths (n = 12) from YEL-AVD in travelers has exceeded the reports of YF (n = 6) acquired by natural infection, raising the question whether the risk of vaccination exceeds the benefit in travelers. To provide some guidance on this point, the rate of vaccine-related injury is compared with the rate of naturally acquired disease in a new analysis that estimates the immunologically susceptible denominator population in YF endemic and epidemic areas. For many years, the risk of vaccine-related illness and death was similar to the risk of illness and death from natural infection with YF in South America. Africa posed a substantially higher estimated risk of wild-type YF than vaccine-related injury. Multiple factors should be considered in making decisions about YF vaccination, including specific destination, season of the year, local evidence for YF transmission, likelihood of exposure to vector mosquitoes and individual risk factors for YEL-AVD, with the goal of increasing vaccine coverage for travel to high-risk areas and reducing unnecessary vaccination. Prospects for future, safer vaccines are also described.
Nipah virus (NiV) disease is a bat-borne zoonosis responsible for outbreaks with high lethality and is a priority for vaccine development. With funding from the Coalition of Epidemic Preparedness ...Innovations (CEPI), we are developing a chimeric vaccine (PHV02) composed of recombinant vesicular stomatitis virus (VSV) expressing the envelope glycoproteins of both Ebola virus (EBOV) and NiV. The EBOV glycoprotein (GP) mediates fusion and viral entry and the NiV attachment glycoprotein (G) is a ligand for cell receptors, and stimulates neutralizing antibody, the putative mediator of protection against NiV. PHV02 is identical in construction to the registered Ebola vaccine (Ervebo) with the addition of the NiV G gene. NiV ephrin B2 and B3 receptors are expressed on neural cells and the wild-type NiV is neurotropic and causes encephalitis in affected patients. It was therefore important to assess whether the NiV G alters tropism of the rVSV vector and serves as a virulence factor. PHV02 was fully attenuated in adult hamsters inoculated by the intramuscular (IM) route, whereas parental wild-type VSV was 100% lethal. Two rodent models (mice, hamsters) were infected by the intracerebral (IC) route with graded doses of PHV02. Comparator active controls in various experiments included rVSV-EBOV (representative of Ebola vaccine) and yellow fever (YF) 17DD commercial vaccine. These studies showed PHV02 to be more neurovirulent than both rVSV-EBOV and YF 17DD in infant animals. PHV02 was lethal for adult hamsters inoculated IC but not for adult mice. In contrast YF 17DD retained virulence for adult mice inoculated IC but was not virulent for adult hamsters. Because of the inconsistency of neurovirulence patterns in the rodent models, a monkey neurovirulence test (MNVT) was performed, using YF 17DD as the active comparator because it has a well-established profile of quantifiable microscopic changes in brain centers and a known reporting rate of neurotropic adverse events in humans. In the MNVT PHV02 was significantly less neurovirulent than the YF 17DD vaccine reference control, indicating that the vaccine will have an acceptable safety profile for humans. The findings are important because they illustrate the complexities of phenotypic assessment of novel viral vectors with tissue tropisms determined by transgenic proteins, and because it is unprecedented to use a heterologous comparator virus (YF vaccine) in a regulatory-enabling study. This approach may have value in future studies of other novel viral vectors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
6.
A Recombinant Vesicular Stomatitis Virus Ebola Vaccine Regules, Jason A; Beigel, John H; Paolino, Kristopher M ...
New England journal of medicine/The New England journal of medicine,
01/2017, Letnik:
376, Številka:
4
Journal Article
Recenzirano
Odprti dostop
This final report updates preliminary data on an attenuated, replication-competent, recombinant vesicular stomatitis virus–based vaccine candidate designed to prevent Ebola virus disease. The results ...supported the safety and immunogenicity of up to two doses of the vaccine.
The worst Ebola virus disease (EVD) outbreak in recorded history has resulted in more than 28,000 cases and 11,000 reported deaths.
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Although the primary strategy to stop the transmission of Ebola remains the identification and isolation of contacts and the use of appropriate personal protective equipment, the development of a safe and efficacious vaccine would provide an important public health tool. Numerous Ebola virus vaccine candidates are in preclinical development, and some have proceeded to human trials.
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An Ebola virus vaccine candidate based on an attenuated, replication-competent, recombinant vesicular stomatitis virus (rVSV) has shown promise in preclinical studies. The . . .
...the analyses by Moritz Kraemer and colleagues4 reported in The Lancet Infectious Diseases provide an important contribution with many practical implications.
This brief review is focused on the events surrounding the initial discovery of a new viral hemorrhagic fever in 1969 and the subsequent 10–15 years during which a substantial understanding of the ...disease was gained. In 1969, a series of sequential life-threating or fatal infections occurred among health care workers in Nigeria and the laboratory scientist who isolated and characterized the causative agent. The agent, Lassa virus was named after the geographical location of the first recognized human case. The new virus was shown to be related to lymphocytic choriomeningitis and to previously unclassified neotropical viruses, including Argentine and Bolivian hemorrhagic fevers, and a new taxonomic grouping, the Arenaviruses, was proposed. In 1970–72, three further epidemics occurred in Nigeria, Liberia and Sierra Leone, the first two involved nosocomial transmission, and the third was a community-based outbreak, during which the rodent reservoir host was identified. In 1976, a long-term research project commenced in Sierra Leone, which produced a rich body of data from prospectively designed studies on the clinical features, transmission, and treatment of the disease.
Summary Background The 2014 Zaire Ebola virus outbreak highlighted the need for a safe, effective vaccine with a rapid onset of protection. We report the safety and immunogenicity of the recombinant ...vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSV∆G-ZEBOV-GP) across a 6 log10 dose range in two sequential cohorts. Methods In this phase 1b double-blind, placebo-controlled, dose-response study we enrolled and randomly assigned healthy adults (aged 18–61 years) at eight study sites in the USA to receive a single injection of vaccine or placebo, administered by intramuscular injection. In cohort 1, participants were assigned to receive 3 × 103 , 3 × 104 , 3 × 105 , or 3 × 106 PFU doses of rVSV∆G-ZEBOV-GP or placebo. In cohort 2, participants were assigned to receive 3 × 106 , 9 × 106 , 2 × 107 , or 1 × 108 PFU doses of rVSV∆G-ZEBOV-GP or placebo. Participants were centrally allocated by the study statistician to vaccine groups or placebo through computer-generated randomisation lists. The primary safety outcome was incidence of adverse events within 14 days in the modified intention-to-treat population (all randomly assigned participants who received vaccine or placebo), and the primary outcome for immunogenicity was IgG ELISA antibody titres at day 28 in the per-protocol population. Surveillance was enhanced for arthritis and dermatitis through to day 56. This study is registered with ClinicalTrials.gov , number NCT02314923. Findings Between Dec 26, 2014, and June 8, 2015, 513 participants were enrolled and randomly assigned; one was not immunised because of unsuccessful phlebotomy. In cohort 1, 256 participants received vaccine (3 × 103 n=64, 3 × 104 n=64, 3 × 105 n=64, or 3 × 106 PFU n=64) and 74 received placebo. In cohort 2, 162 participants received vaccine (3 × 106 n=20, 9 × 106 n=47, 2 × 107 n=47, or 1 × 108 PFU n=48) and 20 received placebo. Most adverse events occurred in the first day after vaccination, and were mild to moderate in intensity, of a short duration, and more frequent at high vaccine doses (9 × 106 PFU and greater). At the 2 × 107 PFU dose (used in phase 3 trials), the most common local adverse events versus placebo within the first 14 days were arm pain (57·4% 27 of 47 vs 7·4% seven of 94) and local tenderness (59·6% 28 of 47 vs 8·5% eight of 94). The most common systemic adverse events at the 2 × 107 PFU dose versus placebo, occurring in the first 14 days, were headache (46·8% 22 of 47 vs 27·7% 26 of 94), fatigue (38·3% 18 of 47 vs 19·1% 18 of 94), myalgia (34·0% 16 of 47 vs 10·6% 10 of 94), subjective fever (29·8% 14 of 47 vs 2·1% two of 94), shivering or chills (27·7% 13 of 47 vs 7·4% seven of 94), sweats (23·4% 11 of 47 vs 3·2% three of 94), joint aches and pain (19·1% nine of 47 vs 7·4% seven of 94), objective fever (14·9% seven of 47 vs 1·1% one of 94), and joint tenderness or swelling (14·9% seven of 47 vs 2·1% two of 94). Self-limited, post-vaccination arthritis occurred in 4·5% (19 of 418) of vaccinees (median onset 12·0 days IQR 10–14; median duration 8·0 days 6–15) versus 3·2% (three of 94) of controls (median onset 15·0 days 6–20; median duration 47·0 days 37–339), with no apparent dose relationship. Post-vaccination dermatitis occurred in 5·7% (24 of 418) of vaccinees (median onset 9·0 days IQR 2–12; median duration 7·0 days 4–9) versus 3·2% (three of 94) of controls (median onset 5·0 days 3–53; median duration 33·0 days 5–370). A low-level, transient, dose-dependent viraemia occurred in concert with early reactogenicity. Antibody responses were observed in most participants by day 14. IgG and neutralising antibody titres were dose-related (p=0·0003 for IgG ELISA and p<0·0001 for the 60% plaque-reduction neutralisation test PRNT60 by linear trend). On day 28 at the 2 × 107 PFU dose, the geometric mean IgG ELISA endpoint titre was 1624 (95% CI 1146–2302) and seroconversion was 95·7% (95% CI 85·5–98·8); the geometric mean neutralising antibody titre by PRNT60 was 250 (176–355) and seroconversion was 95·7% (85·5–98·8). These robust immunological responses were sustained for 1 year. Interpretation rVSV∆G-ZEBOV-GP was well tolerated and stimulated a rapid onset of binding and neutralising antibodies, which were maintained through to day 360. The immunogenicity results support selection of the 2 × 107 PFU dose. Funding Biomedical Advanced Research and Development Authority, US Department of Health and Human Services.
Summary The changing epidemiology of yellow fever and continued reports of rare but serious adverse events associated with yellow fever vaccine have drawn attention to the need to revisit criteria ...for the designation of areas with risk for yellow fever virus activity, and to revise the vaccine recommendations for international travel. WHO convened a working group of international experts to review factors important for the transmission of yellow fever virus and country-specific yellow fever information, to establish criteria for additions to or removal from the list of countries with risk for yellow fever virus transmission, to update yellow fever risk maps, and to revise the recommendations for vaccination for international travel. This report details the recommendations made by the working group about criteria for the designation of risk and specific changes to the classification of areas with risk for transmission of yellow fever virus.
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