Phase II, dose ranging study of the safety and immunogenicity of single dose West Nile vaccine in healthy adults ≥50 years of age

Dayan, Gustavo H.; Bevilacqua, Joan; Coleman, Dorothy; Buldo, Aileen; Risi, George

doi:10.1016/j.vaccine.2012.08.063

Cited by 54 publications

(38 citation statements)

References 38 publications

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“…We observed a lowmagnitude and transient viraemia, similar to that seen in horses, NHPs, and humans [198,286,287]. Peripheral tissue tropism of WNV NSW2011 was restricted predominantly to the draining PLN, while MVE 1-51 was more successful at disseminating to other lymphoid tissues, such as the contralateral PLN and spleen.…”

Section: Discussionsupporting

confidence: 73%

Investigation of neuropathogenesis and control of an equine-pathogenic Australian West Nile virus isolate in an established CD1 Swiss white mouse and a novel rabbit model

Suen¹

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West Nile virus (WNV) is a globally significant mosquito-borne neurotropic virus. In 2011, a large-scale arboviral encephalitis outbreak occurred in Australia, involving close to 1000 horses. A virulent WNV strain, WNV NSW2011 , was isolated from the brain of an encephalitic horse during this outbreak. Preliminary assessment showed that this strain is intermediate in virulence and belongs in the same lineage as the highly virulent North American strains. However, the pathogenesis of WNV in general, let alone this novel Australian strain, remains largely unclear.The first part of the project aimed to investigate the pathogenesis of lethal WNV NSW2011 infection in the established young adult Swiss white (CD1) mouse model, since previous survival challenge experiments demonstrated high lethality (~70%) of WNV NSW2011 in this animal model. I conducted a pilot time-course experiment, which demonstrated only benign pathological and virological outcomes in sacrificed mice on day 3 and 7 post-infection (pi), despite the relatively high lethality seen in previous survival trials. In a subsequent experiment, I characterised the disease phenotype in moribund/dead and surviving mice after WNV NSW2011 infection. Notably, I detected a high degree of intra-group variability in the neuropathology, neural infection and glial cell activation. Even cases with neuroinvasion are typically not fatal, unless underlying co-morbidities or immunosuppressive disease exist.I chose rabbits as a candidate for a novel animal model, due to the ease of performing intra-vital sampling and monitoring, as well as the possibility for tissue sharing in different assays, given the larger size of rabbits than mice. Rabbits are also hind-gut fermenters, and thus may be a better representation of a horse than a mouse. New Zealand White (NZWRs; Oryctolagus cuniculus) and iii North American cottontail rabbits (CTRs; Sylvilagus sp.) were challenged with WNV strains of different virulence (WNV NSW2011 and WNV TX8667 ), and the prototype Murray Valley encephalitis virus strain (MVE 1-51 ), by the footpad route. The rabbits were consistently resistant to developing severe disease after virulent WNV and MVEV infection, regardless of age, gender and species, despite productive virus replication in the draining popliteal lymph node (PLN). The resultant viraemia for all rabbits was also of low magnitude and transient. Furthermore, establishment of virus infection in the brain was not a feature of the disease, despite mild to moderate neuropathology in a subset of rabbits. This capacity to control flavivirus infection may be explained by the rapid antiviral innate immune response detectable by day 3 pi, as well as a fast anti-WNV neutralising antibody response detectable from day 7 pi.Comparisons of the tissue-specific transcriptional profile of important cytokine and chemokine genes suggested that virus control in rabbits was achieved differently depending on the virus, as well as the rabbit species. However, common transcriptional upregulation of IFNγ in...

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Section: Discussionsupporting

confidence: 73%

Investigation of neuropathogenesis and control of an equine-pathogenic Australian West Nile virus isolate in an established CD1 Swiss white mouse and a novel rabbit model

Suen¹

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“…A phase I study in volunteers revealed that ChimeriVax-WN02 was well tolerated and highly immunogenic [33]. Two phase II clinical trials have also been completed with promising results in younger adults and in two older age groups [34,35].…”

Section: Live Attenuatedmentioning

confidence: 99%

Recent advances in human flavivirus vaccines

Scherwitzl

Mongkolsapaja

Screaton

2017

Current Opinion in Virology

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“…To date, two live, attenuated chimeric flavivirus vaccine candidates have been tested in humans [70,120-122]. The first WNV chimeric vaccine to enter clinical trials, ChimeriVax-WN02, was originally developed by Acambis, with testing continued by Sanofi Pasteur following their acquisition of Acambis in 2008.…”

Section: Vaccines In Clinical Developmentmentioning

confidence: 99%

“…Following the Phase I results, two Phase II studies were performed using a plaque purified derivative of ChimeriVax-WN02, which had been developed in an effort to increase attenuation and reduce viremia in vaccinated subjects [121,122]. The first of these trials was divided into two parts, assessing safety and immunogenicity between adult (part 1, ages, 18-40) and older patient populations (part 2, ages, 41-64 or ≥65).…”

Section: Vaccines In Clinical Developmentmentioning

confidence: 99%

Current trends in West Nile virus vaccine development

Amanna

Slifka

2014

Expert Review of Vaccines

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West Nile virus (WNV) is a mosquito-borne flavivirus that has become endemic in the United States. From 1999-2012, there have been 37,088 reported cases of WNV and 1,549 deaths, resulting in a 4.2% case-fatality rate. Despite development of effective WNV vaccines for horses, there is no vaccine to prevent human WNV infection. Several vaccines have been tested in preclinical studies and to date there have been 8 clinical trials, with promising results in terms of safety and induction of antiviral immunity. Although mass vaccination is unlikely to be cost-effective, implementation of a targeted vaccine program may be feasible if a safe and effective vaccine can be brought to market. Further evaluation of new and advanced vaccine candidates is strongly encouraged.

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Phase II, dose ranging study of the safety and immunogenicity of single dose West Nile vaccine in healthy adults ≥50 years of age

Cited by 54 publications

References 38 publications

Investigation of neuropathogenesis and control of an equine-pathogenic Australian West Nile virus isolate in an established CD1 Swiss white mouse and a novel rabbit model

Investigation of neuropathogenesis and control of an equine-pathogenic Australian West Nile virus isolate in an established CD1 Swiss white mouse and a novel rabbit model

Recent advances in human flavivirus vaccines

Current trends in West Nile virus vaccine development

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