Rabies Virus as a Research Tool and Viral Vaccine Vector

Gomme, Emily A.; Wanjalla, Celestine N.; Wirblich, Christoph; Schnell, Matthias J.

doi:10.1016/b978-0-12-387040-7.00009-3

Cited by 38 publications

(24 citation statements)

References 125 publications

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“…Composed of highly immunogenic proteins (Gomme et al, 2011), the virus is prone to quickly enter the nervous system in which it is partially protected against immune responses. Rabies virus has developed a variety of traits to provide for the necessary time to reach and replicate in the CNS.…”

mentioning

confidence: 99%

G gene-deficient single-round rabies viruses for neuronal circuit analysis

Ghanem

Conzelmann

2016

Virus Research

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mentioning

confidence: 99%

G gene-deficient single-round rabies viruses for neuronal circuit analysis

Ghanem

Conzelmann

2016

Virus Research

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“…Since the recent introduction of "reverse genetics" technology (12,13), new live attenuated RABV can be designed, for instance, by gene mutations (see reference 14), duplication or triplication of the RabG gene (15,16), or simultaneous expression of inserted cytokine genes to stimulate the innate immune response (17,18). Some of them are promising candidates of rabies vaccines due to their apathogenicity and improved immunogenicity in animal models.…”

mentioning

confidence: 99%

A New Rabies Vaccine Based on a Recombinant Orf Virus (Parapoxvirus) Expressing the Rabies Virus Glycoprotein

Amann

Rohde

Wulle

et al. 2013

J Virol

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The present study describes the generation of a new Orf virus (ORFV) recombinant, D1701-V-RabG, expressing the rabies virus (RABV) glycoprotein that is correctly presented on the surface of infected cells without the need of replication or production of infectious recombinant virus. One single immunization with recombinant ORFV can stimulate high RABV-specific virus-neutralizing antibody (VNA) titers in mice, cats, and dogs, representing all nonpermissive hosts for the ORFV vector. The protective immune response against severe lethal challenge infection was analyzed in detail in mice using different dosages, numbers, and routes for immunization with the ORFV recombinant. Long-term levels of VNA could be elicited that remained greater than 0.5 IU per ml serum, indicative for the protective status. Single applications of higher doses (10 7 PFU) can be sufficient to confer complete protection against intracranial (i.c.) challenge, whereas booster immunization was needed for protection by the application of lower dosages. Anamnestic immune responses were achieved by each of the seven tested routes of inoculation, including oral application. Finally, in vivo antibody-mediated depletion of CD4-positive and/or CD8-posititve T cell subpopulations during immunization and/or challenge infection attested the importance of CD4 T cells for the induction of protective immunity by D1701-V-RabG. This report demonstrates another example of the potential of the ORFV vector and also indicates the capability of the new recombinant for vaccination of animals.

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“…In contrast to many other vector platforms, the immune response against the RABV vector constitutes an added value, as it confers protection from rabies (49). Wild carnivores are considered an important RABV reservoir, which, often via infection of domestic dogs, is the root cause of human rabies in developing countries (50,51).…”

Section: Efficacy Of Bivalent Rabv-cdv Vaccines Journal Of Virologymentioning

confidence: 99%

Inactivated Recombinant Rabies Viruses Displaying Canine Distemper Virus Glycoproteins Induce Protective Immunity against Both Pathogens

Budaszewski

Hudacek

Sawatsky

et al. 2017

J Virol

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The development of multivalent vaccines is an attractive methodology for the simultaneous prevention of several infectious diseases in vulnerable populations. Both canine distemper virus (CDV) and rabies virus (RABV) cause lethal disease in wild and domestic carnivores. While RABV vaccines are inactivated, the liveattenuated CDV vaccines retain residual virulence for highly susceptible wildlife species. In this study, we developed recombinant bivalent vaccine candidates based on recombinant vaccine strain rabies virus particles, which concurrently display the protective CDV and RABV glycoprotein antigens. The recombinant viruses replicated to near-wild-type titers, and the heterologous glycoproteins were efficiently expressed and incorporated in the viral particles. Immunization of ferrets with beta-propiolactone-inactivated recombinant virus particles elicited protective RABV antibody titers, and animals immunized with a combination of CDV attachment protein-and fusion protein-expressing recombinant viruses were protected from lethal CDV challenge. However, animals that were immunized with only a RABV expressing the attachment protein of CDV vaccine strain Onderstepoort succumbed to infection with a more recent wild-type strain, indicating that immune responses to the more conserved fusion protein contribute to protection against heterologous CDV strains.IMPORTANCE Rabies virus and canine distemper virus (CDV) cause high mortality rates and death in many carnivores. While rabies vaccines are inactivated and thus have an excellent safety profile and high stability, live-attenuated CDV vaccines can retain residual virulence in highly susceptible species. Here we generated recombinant inactivated rabies viruses that carry one of the CDV glycoproteins on their surface. Ferrets immunized twice with a mix of recombinant rabies viruses carrying the CDV fusion and attachment glycoproteins were protected from lethal CDV challenge, whereas all animals that received recombinant rabies viruses carrying only the CDV attachment protein according to the same immunization scheme died. Irrespective of the CDV antigens used, all animals developed protective titers against rabies virus, illustrating that a bivalent rabies virus-based vaccine against CDV induces protective immune responses against both pathogens.

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Rabies Virus as a Research Tool and Viral Vaccine Vector

Cited by 38 publications

References 125 publications

G gene-deficient single-round rabies viruses for neuronal circuit analysis

G gene-deficient single-round rabies viruses for neuronal circuit analysis

A New Rabies Vaccine Based on a Recombinant Orf Virus (Parapoxvirus) Expressing the Rabies Virus Glycoprotein

Inactivated Recombinant Rabies Viruses Displaying Canine Distemper Virus Glycoproteins Induce Protective Immunity against Both Pathogens

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