Inactivated or Live-Attenuated Bivalent Vaccines That Confer Protection against Rabies and Ebola Viruses

Blaney, Joseph E.; Wirblich, Christoph; Papaneri, Amy B.; Johnson, Reed F.; Myers, C.; Juelich, Terry L.; Holbrook, Michael R.; Freiberg, Alexander N.; Bernbaum, John G.; Jahrling, Peter B.; Paragas, Jason; Schnell, Matthias J.

doi:10.1128/jvi.00558-11

Cited by 86 publications

(113 citation statements)

References 49 publications

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“…The vaccine candidates were avirulent in adult mice and displayed low neurovirulence in suckling mice. Another study also demonstrated that 5 £ 10 5 FFU of this vaccine could induce humoral immunity and conferred protection from both RABV and EBOV after intraperitoneal challenging with 1000 PFU of mouse-adapted EBOV in mice 68 (Table 3). In 2013, a study immunized NHPs with a platform based on replication competent RABV, replicationdeficient RABV, or chemically inactivated RABV expressing EBOV GP.…”

Section: Rvsv-ebovmentioning

confidence: 92%

Ebola vaccines in clinical trial: The promising candidates

Wang

et al. 2016

Human Vaccines & Immunotherapeutics

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Ebola virus disease (EVD) has become a great threat to humans across the world in recent years. The 2014 Ebola epidemic in West Africa caused numerous deaths and attracted worldwide attentions. Since no specific drugs and treatments against EVD was available, vaccination was considered as the most promising and effective method of controlling this epidemic. So far, 7 vaccine candidates had been developed and evaluated through clinical trials. Among them, the recombinant vesicular stomatitis virusbased vaccine (rVSV-EBOV) is the most promising candidate, which demonstrated a significant protection against EVD in phase III clinical trial. However, several concerns were still associated with the Ebola vaccine candidates, including the safety profile in some particular populations, the immunization schedule for emergency vaccination, and the persistence of the protection. We retrospectively reviewed the current development of Ebola vaccines and discussed issues and challenges remaining to be investigated in the future.

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Section: Rvsv-ebovmentioning

confidence: 92%

Ebola vaccines in clinical trial: The promising candidates

Wang

et al. 2016

Human Vaccines & Immunotherapeutics

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“…The vaccine candidates were shown to be avirulent in adult mice and displayed low neurovirulence in suckling mice [70]. These vaccines also could induce humoral immunity and conferred protection from both RABV and EBOV lethal challenge in mice [71]. Furthermore, pre-existing immunity against RABV did not impact the immunogenicity of these vaccines in mice [72].…”

Section: Recombinant Rabies Virus (Rabv)-based Vaccinesmentioning

confidence: 95%

Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease

Yao

et al. 2015

Cell Physiol Biochem

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Ebolaviruses are highly infectious pathogens that cause lethal Ebola virus disease (EVD) in humans and non-human primates (NHPs). Due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. In this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vaccines, DNA vaccines, Ebola virus-like particles (VLPs), vaccinia virus-based vaccines, Venezuelan equine encephalitis virus (VEEV)-like replicon particles, Kunjin virus-based vaccine, recombinant Zaire Ebolavirus∆VP30, recombinant cytomegalovirus (CMV)-based vaccines, recombinant rabies virus (RABV)-based vaccines, recombinant paramyxovirus-based vaccines, adenovirus-based vaccines and vesicular stomatitis virus (VSV)-based vaccines. No licensed vaccine or specific treatment is currently available to counteract ebolavirus infection, although DNA plasmids and several viral vector approaches have been evaluated as promising vaccine platforms. These vaccine candidates have been confirmed to be successful in protecting NHPs against lethal infection. Moreover, these vaccine candidates were successfully advanced to clinical trials. The present review provides an update of the current research on Ebola vaccines, with the aim of providing an overview on current prospects in the fight against EVD.

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“…Full-length genomic cDNA constructs were based on the pcBNSP-333 backbone described previously (24,60). The open reading frames from the CDV F and H genes were cloned from plasmids pCG-Fos, pCG-F5804P, pCG-Hos, and pCG-H5804P (59) while inserting 5= BsiWI and 3= NheI restriction sites (Fig.…”

Section: Methodsmentioning

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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Inactivated or Live-Attenuated Bivalent Vaccines That Confer Protection against Rabies and Ebola Viruses

Cited by 86 publications

References 49 publications

Ebola vaccines in clinical trial: The promising candidates

Ebola vaccines in clinical trial: The promising candidates

Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease

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

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