Chimeric Lyssavirus Glycoproteins with Increased Immunological Potential

Jallet, Corinne; Jacob, Yves; Bahloul, Chokri; Drings, Astrid; Desmézières, Emmanuel; Tordo, Noël; Perrin, Pierre

doi:10.1128/jvi.73.1.225-233.1999

Cited by 78 publications

(39 citation statements)

References 37 publications

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“…Likewise, switching of epitopes between lyssavirus envelope G can allow further cross neutralisation studies to be undertaken, an important aspect in vaccine design. The ability to switch domains of the lyssavirus envelope G has already been explored, highlighting the potential for use in antigenic studies (Jallet et al, 1999). This will enable the level of protection afforded against other divergent lyssaviruses in phylogroup II and III to be evaluated, of great interest from a public health perspective due to their unknown disease burden.…”

Section: Discussionmentioning

confidence: 99%

Generation of Arctic-like Rabies Viruses Containing Chimeric Glycoproteins Enables Serological Potency Studies

Horton

et al. 2017

Preprint

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Rabies viruses have the highest case fatality rate of any known virus and are responsible for an estimated 60,000 deaths each year. This is despite the fact that there are highly efficacious vaccines and postexposure prophylaxis available. However, while it is assumed these biologics provide protection against all rabies virus isolates, there are certain subdivisions of RABV lineages, such as within the Arctic-like RABV (AL rabies virus lineage, where data is limited and thus the potency of existing biologics has not been thoroughly assessed. By fusing the Arctic-like rabies virus envelope glycoprotein ecto- and transmembrane domains with the vesicular stomatitis virus cytoplasmic domain, a high titre (7.7 x 105 − 6.1 x 106 RLU/ml) pseudotyped virus was generated that was subsequently used in a pseudotyped virus neutralisation assay. These results showed that Arctic-like rabies viruses are neutralised to human, canine and feline vaccines and human post-exposure prophylaxis and this was not influenced by the swapping of the cytoplasmic domains (CVS-11 vs CVS-11etmVSVc; r = 0.99, p < 0.0001). This study supports the concept that rabies virus vaccines and newly identified mAbs are able to neutralise rabies virus variants that cluster in a monophyletic clade, referred to as phylogroup I lyssaviruses.

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Section: Discussionmentioning

confidence: 99%

Generation of Arctic-like Rabies Viruses Containing Chimeric Glycoproteins Enables Serological Potency Studies

Horton

et al. 2017

Preprint

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“…• RABV glycoprotein expressed by canine adenovirus [32]. • A chimeric lyssavirus glycoprotein with segments derived from RABV and Mokola virus that provide immunization against more than one lyssavirus [33]. • DNA vaccination with RABV glycoprotein cloned into a plasmid vector [34].…”

Section: Alternative Development Of Rabies Vaccinesmentioning

confidence: 99%

Developments in rabies vaccines

Hicks

Fooks

Johnson

2012

Clinical and Experimental Immunology

106

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Summary The development of vaccines that prevent rabies has a long and distinguished history, with the earliest preceding modern understanding of viruses and the mechanisms of immune protection against disease. The correct application of inactivated tissue culture‐derived vaccines is highly effective at preventing the development of rabies, and very few failures are recorded. Furthermore, oral and parenteral vaccination is possible for wildlife, companion animals and livestock, again using inactivated tissue culture‐derived virus. However, rabies remains endemic in many regions of the world and causes thousands of human deaths annually. There also remain no means of prophylaxis for rabies once the virus enters the central nervous system (CNS). One reason for this is the poor immune response within the CNS to infection with rabies virus (RABV). New approaches to vaccination using modified rabies viruses that express components of the innate immune system are being applied to this problem. Preliminary reports suggest that direct inoculation of such viruses could trigger an effective anti‐viral response and prevent a fatal outcome from RABV infection.

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“…antigen-capture or sandwich) ELISA using a RABV neutralizing monoclonal antibody (MAb) emerged as a preferred method [16,17]. Using a MAb that only recognizes the native, trimeric and immunogenic form of RABV G prevents detection of non-immunogenic, soluble, G in vaccines [18][19][20][21]. Recently, this method has been further refined using a single-chain variable fragment antibody [22] or a diabody, to replace MAbs for antigen capture [23].…”

Section: Introductionmentioning

confidence: 99%

An electrochemiluminescence assay for analysis of rabies virus glycoprotein content in rabies vaccines

Smith

Ellison

et al. 2013

Vaccine

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Vaccine potency testing is necessary to evaluate the immunogenicity of inactivated rabies virus (RABV) vaccine preparations before human or veterinary application. Currently, the NIH test is recommended by the WHO expert committee to evaluate RABV vaccine potency. However, numerous disadvantages are inherent concerning cost, number of animals and biosafety requirements. As such, several in vitro methods have been proposed for the evaluation of vaccines based on RABV glycoprotein (G) quality and quantity, which is expected to correlate with vaccine potency. In this study an antigen-capture electrochemiluminescent (ECL) assay was developed utilizing anti-RABV G monoclonal antibodies (MAb) to quantify RABV G. One MAb 2-21-14 was specific for a conformational epitope so that only immunogenic, natively folded G was captured in the assay. MAb 2-21-14 or a second MAb (62-80-6) that binds a linear epitope was used for detection of RABV G. Vaccine efficacy was also assessed in vivo using pre-exposure vaccination of mice. Purified native RABV G induced a RABV neutralizing antibody (rVNA) response with a geometric mean titer of 4.2IU/ml and protected 100% of immunized mice against RABV challenge, while an experimental vaccine with a lower quality and quantity of G induced a rVNA titer<0.05IU/ml and protected <50% of immunized mice. These preliminary results support the hypothesis that in vivo immunogenicity may be predicted from the in vitro measurement of RABV G using an ECL assay. Based upon these results, the ECL assay may have utility in replacement of the NIH test.

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Chimeric Lyssavirus Glycoproteins with Increased Immunological Potential

Cited by 78 publications

References 37 publications

Generation of Arctic-like Rabies Viruses Containing Chimeric Glycoproteins Enables Serological Potency Studies

Generation of Arctic-like Rabies Viruses Containing Chimeric Glycoproteins Enables Serological Potency Studies

Developments in rabies vaccines

An electrochemiluminescence assay for analysis of rabies virus glycoprotein content in rabies vaccines

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