Clinical proof of principle for ChimeriVax™: recombinant live, attenuated vaccines against flavivirus infections

Monath, Thomas P.; McCarthy, Karen; Bedford, Philip; Johnson, Casey; Nichols, Richard A.; Yoksan, Sutee; Marchesani, Ron; Knauber, Michael; Wells, Keith H.; Arroyo, Juan; Guirakhoo, Farshad

doi:10.1016/s0264-410x(01)00457-1

Cited by 209 publications

(147 citation statements)

References 32 publications

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“…Further studies of innate immune responses in NHP using transcriptomic profiling and T-cell responses in mice are in progress and will be reported elsewhere. Initial preclinical data on ChimeriVax vaccines in NHP suggested that anti-vector (YF) preimmunity could represent a concern (26), which, however, was completely dispelled in subsequent clinical trials (23,24). Here we demonstrated that the effect of WN preimmunity on the effectiveness of RV-WN/TBE was less pronounced compared with the effect of YF preimmunity on ChimeriVax controls in mice.…”

Section: Discussionmentioning

confidence: 66%

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Single-dose vaccine against tick-borne encephalitis

Rumyantsev¹,

Goncalvez²,

Giel–Moloney³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Tick-borne encephalitis (TBE) virus is the most important human pathogen transmitted by ticks in Eurasia. Inactivated vaccines are available but require multiple doses and frequent boosters to induce and maintain immunity. Thus far, the goal of developing a safe, live attenuated vaccine effective after a single dose has remained elusive. Here we used a replication-defective (single-cycle) flavivirus platform, RepliVax, to generate a safe, single-dose TBE vaccine. Several RepliVax-TBE candidates attenuated by a deletion in the capsid gene were constructed using different flavivirus backbones containing the envelope genes of TBE virus. RepliVax-TBE based on a West Nile virus backbone (RV-WN/TBE) grew more efficiently in helper cells than candidates based on Langat E5, TBE, and yellow fever 17D backbones, and was found to be highly immunogenic and efficacious in mice. Live chimeric yellow fever 17D/TBE, Dengue 2/TBE, and Langat E5/TBE candidates were also constructed but were found to be underattenuated. RV-WN/TBE was demonstrated to be highly immunogenic in Rhesus macaques after a single dose, inducing a significantly more durable humoral immune response compared with three doses of a licensed, adjuvanted human inactivated vaccine. Its immunogenicity was not significantly affected by preexisting immunity against WN. Immunized monkeys were protected from a stringent surrogate challenge. These results support the identification of a single-cycle TBE vaccine with a superior product profile to existing inactivated vaccines, which could lead to improved vaccine coverage and control of the disease.flavivirus vaccine | prophylaxis | preclinical | nonhuman primate

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Section: Discussionmentioning

confidence: 66%

“…Previous data indicate that anti-vector (YF) preimmunity is not of concern for ChimeriVax vaccines in humans (23,24). However, this aspect has not been examined in mice.…”

mentioning

confidence: 99%

Single-dose vaccine against tick-borne encephalitis

Rumyantsev¹,

Goncalvez²,

Giel–Moloney³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Indeed, clinical trials have shown that YF17D-JE is safe and immunogenic with a single dose providing long-lasting immunity to wild-type strains of JE virus. [48][49][50][51] This recombinant technology-based vaccine was licensed for human use in Australia (Imojev-Sanofi-Pasteur). Accordingly, YF17D-WN chimeric viruses have also undergone clinical tests.…”

Section: Replacement Of Yf17d Structural Genes With Those Of Other Flmentioning

confidence: 99%

The yellow fever 17D virus as a platform for new live attenuated vaccines

Bonaldo

Sequeira

Galler³

2014

Human Vaccines & Immunotherapeutics

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“…the investigators have been working in vaccines with attenuated live viruses, different types of chimerical viruses such as yellow fever / dengue (Monath et al, 2002) and dengue / dengue, among others, inactivated complete virus, dna vaccines and vaccines of subunits. at least seven of these projects are already in the stage of clinical trials phase II and other projects are in the Preclinical Phase, evaluating vaccinal candidates in primates.…”

Section: Vaccines Against Dengue?mentioning

confidence: 99%

Dengue

Torres

2008

Estud. av.

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El dengue es hoy la más importante arbovirosis, por su gran carga de enfermedad e implicaciones sociales. El mosquito Aedes aegypti, su principal transmisor convive con el hombre en su hábitat domestico y peridoméstico. El cuadro clínico es de fiebre, cefalea, dolor retroocular, dolores corporales, exantema y mucho decaimiento. El enfermo puede empeorar súbitamente y presentar choque por dengue, con grandes hemorragias digestivas y elevada mortalidad. No existe droga antiviral, pero la muerte puede evitarse mediante la infusión intravenosa precoz de soluciones cristaloides. Algunos candidatos vacunales están actualmente en ensayo clínico. La prevención depende del control del vector, mediante educación sanitaria y reordenamiento ambiental.

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Clinical proof of principle for ChimeriVax™: recombinant live, attenuated vaccines against flavivirus infections

Cited by 209 publications

References 32 publications

Single-dose vaccine against tick-borne encephalitis

Single-dose vaccine against tick-borne encephalitis

The yellow fever 17D virus as a platform for new live attenuated vaccines

Dengue

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