The wide utility of rabbits as models of human diseases

Wildlife Research, 2007

Currently available vaccines against myxomatosis and rabbit hemorrhagic disease virus (RHDV) are not suited to immunise wild rabbit populations, as vaccines need to be delivered individually by conventional veterinary practices. As an alternative approach, research in Spain has focused on the development of a transmissible vaccine. A recombinant virus has been constructed based on a naturally attenuated myxoma virus (MV) field strain, expressing the RHDV capsid protein (VP60). Following inoculation of rabbits, the recombinant virus (MV-VP60) induced specific antibody responses against MV and RHDV, conferring protection against lethal challenges with both viruses. Furthermore, the recombinant MV-VP60 virus showed a limited horizontal transmission capacity, either by direct contact or in a fleamediated process, promoting immunisation of contact uninoculated animals. Efficacy and safety of the vaccine have been extensively evaluated under laboratory conditions and in a limited field trial. The development of the transmissible vaccine strategy and the steps being taken to obtain the marketing authorisation for the vaccine in the European Union are presented in this review.

Vaccine, 2001

As a novel approach for immunisation of wild rabbits, we have recently developed a transmissible vaccine against myxomatosis and rabbit hemorrhagic disease (RHD) based on a recombinant myxoma virus (MV) expressing the RHDV capsid protein [J. Virol. 74 (2000) 1114]. The efficacy and safety of the vaccine have been extensively evaluated under laboratory conditions. In this study, we report the first limited field trial of the candidate vaccine that was undertaken in an island of 34 Has containing a population of around 300 rabbits. Following administration by the subcutaneous route to 76 rabbits, the vaccine induced specific antibody responses against both myxomatosis and RHDV in all the inoculated rabbits. Furthermore, the recombinant virus exhibited a limited horizontal transmission capacity, promoting seroconversion of around 50% of the uninoculated rabbit population. No evidence of undesirable effects due to the recombinant virus field release was detected.

2004

Veterinary Microbiology, 2015

Ovine herpesvirus-2 (OvHV-2) is the etiological agent of sheep-associated malignant catarrhal fever (SA-MCF), a fatal lymphoproliferative disease of many species in the order Artiodactyla. Development of a vaccine is critical to prevent mortality. Because OvHV-2 has not been cultured in vitro, SA-MCF research is hindered by the lack of in vitro tools to study viral constituents and specific host immune responses. As an alternative, in this study the neutralizing activity of antibodies against OvHV-2 glycoproteins gB and gH/gL was evaluated in vivo using rabbits. OvHV-2-specific antibodies were developed in rabbits by immunization using biolistic delivery of plasmids expressing the genes of interest. A lethal dose of OvHV-2 was incubated with the antisera and then nebulized into rabbits. Virus neutralization was assessed by measuring infection parameters associated with the virus infectious dose. Anti-gB or anti-gH/gL antibodies alone blocked infection in five out of six rabbits (83%), while a combination of anti-gB and anti-gH/gL antibodies protected all six rabbits (100%) from infection. These results indicate that antibodies to OvHV-2 gB and gH/gL are capable of neutralizing virions, and consequently, reduce virus infectivity and prevent SA-MCF in rabbits. Thus, OvHV-2 gB and gH/gL are suitable targets to be tested in a SA-MCF vaccine aimed at stimulating neutralizing antibody responses.

European Journal of Immunology, 1976

The amino acid sequence of 5 light (L) chain (b4) variable (VL) regions and the partial sequence of VL (K) regions from 12 anti-streptococcal group A-variant polysaccharide (Av-CHO) and 2 anti-streptococcal group C polysaccharide (C-CHO) antibodies was determined. These sequences contain 70 invariant positions as opposed to 50 invariant positions in other rabbit VL regions. Variability within the framework residues lacks randomness, and parent offspring relationship or otherwise close familial relationship is apparent in several instances. Variability in the complementarity-determining regions is reduced by 2.3-5.5-fold in comparison with other rabbit L-chains with several identical first and third hypervariable regions. Residue positions 50-56, known to mark the second hypervariable region in human K-chains, are not hypervariable in L-chains from Av-CHO rabbit antibodies. Considering the 67 rabbit L-chain sequences, completely or partially known today, for counting the number of V region germ line genes, it is concluded that the species rabbit has at least 27 VL germ line genes available.

Applied Sciences, 2020

Production of immunodeficient (ID) models in non-murine animal species had been extremely challenging until the advent of gene-editing tools: first zinc finger nuclease (ZFN), then transcription activator-like effector nuclease (TALEN), and most recently clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR)/Cas9. We and others used those gene-editing tools to develop ID rabbits carrying a loss of function mutation in essential immune genes, such as forkhead box protein N1 (FOXN1), recombination activating gene 1/2 (RAG1/2), and interleukin 2 receptor subunit gamma (IL2RG). Like their mouse counterparts, ID rabbits have profound defects in their immune system and are prone to bacterial and pneumocystis infections without prophylactic antibiotics. In addition to their use as preclinical models for primary immunodeficient diseases, ID rabbits are expected to contribute significantly to regenerative medicine and cancer research, where they serve as reci...

Journal of Biological Chemistry, 2000

The rabbit antibody repertoire, which in the form of polyclonal antibodies has been used in diagnostic applications for decades, would be an attractive source for the generation of therapeutic human antibodies. The humanization of rabbit antibodies, however, has not been reported. Here we use phage display technology to select and humanize antibodies from rabbits that were immunized with human A33 antigen which is a target antigen for the immunotherapy of colon cancer. We first selected rabbit antibodies that bind to a cell surface epitope of human A33 antigen with an affinity in the 1 nM range. For rabbit antibody humanization, we then used a selection strategy that combines grafting of the complementarity determining regions with framework fine tuning. The resulting humanized antibodies were found to retain both high specificity and affinity for human A33 antigen.

Journal of Virology, 2000

We have developed a new strategy for immunization of wild rabbit populations against myxomatosis and rabbit hemorrhagic disease (RHD) that uses recombinant viruses based on a naturally attenuated field strain of myxoma virus (MV). The recombinant viruses expressed the RHDV major capsid protein (VP60) including a linear epitope tag from the transmissible gastroenteritis virus (TGEV) nucleoprotein. Following inoculation, the recombinant viruses induced specific antibody responses against MV, RHDV, and the TGEV tag. Immunization of wild rabbits by the subcutaneous and oral routes conferred protection against virulent RHDV and MV challenges. The recombinant viruses showed a limited horizontal transmission capacity, either by direct contact or in a flea-mediated process, promoting immunization of contact uninoculated animals.

Innovation in Vaccinology, 2012

Ef fi cient translation of basic vaccine research into clinical therapies greatly depends upon the availability of appropriate animal models. Testing novel vaccine candidates in animal models is a critical step in the development of modern vaccines. Animal models are being used to assess the quality and quantity of the immune response, to identify the optimal route of delivery and formulation, to determine protection from infection and disease transmission, and to evaluate the safety and toxicity of the vaccine formulation. Animal models help to make the translation from basic research to clinical application, and they often allow prediction of the vaccine potential, which helps in predicting the fi nancial risks for vaccine manufacturers. Choosing an appropriate animal model has become increasingly important for the fi eld, as each model has its own advantages and disadvantages. In this review, the criteria for selecting the right animal model, the advantages and disadvantages of various animal models, as well as the future needs for animal models are being discussed.

World’s Veterinary Journal, 2022

Rabbit hemorrhagic disease is a fatal threat to rabbits that causes sustainability problems and substantial economic losses. The aim of the current study was to compare the immuno-enhancing effects of a bivalent inactivated rabbit hemorrhagic disease virus (RHDV) vaccine adjuvanted with Montanide with an inactivated RHDV vaccine with an aluminum hydroxide gel. Montanide incomplete seppic adjuvant 71 VG was prepared as an oil emulsion, and several batches adjuvanted with an aluminum hydroxide gel were prepared. Then, 250 New Zealand rabbits aged 6 weeks were randomly allocated to three groups. Group 1 was subjected to the bivalent inactivated RHDV adjuvanted with an aluminum hydroxide gel, Group 2 received the oil-emulsion vaccine adjuvanted with Montanide, and Group 3 was left unvaccinated as a negative control group. Efficacy was determined using a hemagglutination inhibition test, and resistance was determined using virulent RHDVa and RHDV2. The clinical signs included sudden death, nervous manifestations, aimless running, lateral recumbence, and crying before death. The mortality rates were recorded at 3 weeks, 3 months, 6 months, and 12 months after vaccination. In addition, blood samples were collected on the first day as well as 1, 2, 3, 4, 6 weeks post-vaccination (WPV), and 2, 3, 4 month post-vaccination (MPV) until 12 MPV. Serological analysis indicated that the bivalent inactivated RHDV oil-emulsion vaccine was more effective than the bivalent inactivated RHDV aluminum hydroxide gel vaccine, resulting in improved immune responses and longer-lasting protective immunological responses in vaccinated rabbits. The bivalent inactivated RHDV oil-emulsion vaccine was also sterile and safe and helped the protection of the rabbits against RHDVa and RHDV2, hence reducing the time and effort required during the vaccination process and reducing the levels of discomfort for the rabbits.