Immunization of mice with the non-toxic HC50 domain of botulinum neurotoxin presented by rabies virus particles induces a strong immune response affording protection against high-dose botulinum neurotoxin challenge

Mustafa, Waleed; Al-Saleem, Fetweh H.; Nasser, Zidoon; Olson, Rebecca M.; Mattis, Jeffrey A.; Simpson, Lance L.; Schnell, Matthias J.

doi:10.1016/j.vaccine.2011.04.045

Cited by 21 publications

(28 citation statements)

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“…Neuroinvasiveness describes the ability of a virus to invade the CNS when inoculated at a peripheral site, while neurovirulence describes the capacity of a virus to induce disease when administered directly into the brain. While live RABV vaccine vectors have previously been used as a safe and efficacious platform to generate vaccine candidates against several pathogens (Faber et al, 2005;Faul et al, 2009;McGettigan et al, 2003;Mustafa et al, 2011;Siler et al, 2002), we sought here to fully characterize the viral pathogenesis and safety of our RABV/EBOV vaccine candidates in comparison to the live RABV vaccine that has been used extensively for wildlife vaccination in Europe.…”

Section: Discussionmentioning

confidence: 99%

A replication-deficient rabies virus vaccine expressing Ebola virus glycoprotein is highly attenuated for neurovirulence

et al. 2012

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We are developing inactivated and live-attenuated rabies virus (RABV) vaccines expressing Ebola virus (EBOV) glycoprotein for use in humans and endangered wildlife, respectively. Here, we further characterize the pathogenesis of the live-attenuated RABV/EBOV vaccine candidates in mice in an effort to define their growth properties and potential for safety. RABV vaccines expressing GP (RV-GP) or a replication-deficient derivative with a deletion of the RABV G gene (RVΔG-GP) are both avirulent after intracerebral inoculation of adult mice. Furthermore, RVΔG-GP is completely avirulent upon intracerebral inoculation of suckling mice unlike parental RABV vaccine or RV-GP. Analysis of RVΔG-GP in the brain by quantitative PCR, determination of virus titer, and immunohistochemistry indicated greatly restricted virus replication. In summary, our findings indicate that RV-GP retains the attenuation phenotype of the live-attenuated RABV vaccine, and RVΔG-GP would appear to be an even safer alternative for use in wildlife or consideration for human use.

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Section: Discussionmentioning

confidence: 99%

A replication-deficient rabies virus vaccine expressing Ebola virus glycoprotein is highly attenuated for neurovirulence

et al. 2012

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“…CDV wild-type strain 5804P (56), its enhanced green fluorescent protein (eGFP)-expressing derivative 5804PeH (57), and eGFP-expressing vaccine strain Onderstepoort (OSeH) (58) were grown in VerodogSLAMtag cells. CDV F and H proteins were detected by using rabbit anti-Fcyt or anti-Hcyt antibodies described previously (59), and peptide-specific antibodies described previously (26) were used to detect RABV M and actin.…”

Section: Methodsmentioning

confidence: 99%

“…Pelleted viruses were resuspended in Dulbecco's phosphate-buffered saline (D-PBS; Mediatech) overnight at 4°C. Viruses were inactivated by incubation with ␤-propiolactone (Sigma) as described previously (26).…”

Section: Methodsmentioning

confidence: 99%

“…The RABV SAD-B19 vaccine strain (23) used in this study has been further attenuated by a mutation of arginine to glycine at position 333 of the G glycoprotein (24,25). Since the production and ␤-propiolactone inactivation process of RABV vaccines are well established (26), they represent an excellent platform for the development of inactivated bivalent vaccines that also protect against other pathogens (23,27). Toward this, we assessed the safety and efficacy of the different RABV-CDV vaccine candidates in ferrets.…”

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confidence: 99%

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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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“…In terms of future developments, in addition to Hc-derived vaccines, some other recombinant subunit vaccines such as those consisting of combined catalytic and translocation domains (LCH N ) or ones coupled to viral vectors for enhanced immunogenicity (Mustafa et al 2011) may be candidates for vaccine development. Another development that should not be ignored is the mucosal delivery of vaccines against BoNT poisoning.…”

Section: Recombinant Vaccinesmentioning

confidence: 99%

Biological Toxins and Bioterrorism

Gopalakrishnakone¹,

Balali-Mood²,

Llewellyn³

et al. 2015

Toxinology

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In recent years, the field of toxinology has expanded substantially. On the one hand it studies venomous animals, plants and micro organisms in detail to understand their mode of action on targets. While on the other, it explores the biochemical composition, genomics and proteomics of toxins and venoms to understand their three interaction with life forms (especially humans), development of antidotes and exploring their pharmacological potential. Therefore, toxinology has deep linkages with biochemistry, molecular biology, anatomy and pharmacology. In addition, there is a fast-developing applied subfield, clinical toxinology, which deals with understanding and managing medical effects of toxins on human body. Given the huge impact of toxin-based deaths globally, and the potential of venom in generation of drugs for so-far incurable diseases (for example, diabetes, chronic pain), the continued research and growth of the field is imminent. This has led to the growth of research in the area and the consequent scholarly output by way of publications in journals and books. Despite this ever-growing body of literature within biomedical sciences, there is still no all-inclusive reference work available that collects all of the important biochemical, biomedical and clinical insights relating to toxinology. Composed of 11 volumes, Toxinology provides comprehensive and authoritative coverage of the main areas in toxinology, from fundamental concepts to new developments and applications in the field. Each volume comprises a focused and carefully chosen collection of contributions from leading names in the subject.

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Immunization of mice with the non-toxic HC50 domain of botulinum neurotoxin presented by rabies virus particles induces a strong immune response affording protection against high-dose botulinum neurotoxin challenge

Cited by 21 publications

References 50 publications

A replication-deficient rabies virus vaccine expressing Ebola virus glycoprotein is highly attenuated for neurovirulence

A replication-deficient rabies virus vaccine expressing Ebola virus glycoprotein is highly attenuated for neurovirulence

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

Biological Toxins and Bioterrorism

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