Measures to minimise RHDV1 infection in pet ‘domestic’ rabbits

Main outcomes from the review of the protection of pet rabbits from RHDV1 K5

  • The current vaccine (Cylap) has a proven 20 year track record in Australia and 30 years in Europe protecting rabbits from all RHDV1 strains.
  • The World Organisation for Animal Health (OIE) provides strong support that existing vaccines provide good protection against genotype 1 strains of RHDV (ie conventional and RHDVa variants, which includes RHDV1 K5).
  • RHDV1 K5, scheduled to be released in March 2017, is an RHDV1 strain and the current vaccine has been shown to provide protection against this strain.
  • Evidence of the vaccines’ effectiveness in protecting rabbits from RHDV1 K5 has been scientifically validated in NSW DPI studies.
  • Statistical analysis of this data showed vaccination delivers a highly significant effect on the survival of rabbits exposed to the virus. In other words, statistical analysis of this data shows that vaccinated rabbits will survive exposure to RHDV1 K5.
  • Taking into account all field and experimental data that is available, there is considered to be a substantial weight of evidence to support the efficacy of inactivated RHDV vaccines against RHDV1s and the new RHDV1 K5 strain, for which release is planned in March 2017.
  • There is no field or experimental evidence to suggest that the currently available vaccine will not provide protection against the new K5 release strain.

Background situation

Rabbit haemorrhagic disease virus (RHDV) comprises two major types:

  1. RHDV Type 1 (or RHDV1) strains made up of conventional and RHDVa variants, and
  2. Significantly different RHDV Type 2 (or RHDV2).

Conventional rabbit haemorrhagic disease virus 1 (RHDV1) – the Czech strain – was released and has been circulating in the Australian rabbit population since 1996. A commercially available vaccine has been available for use in pet and farmed rabbits since that time. There are no records or expert knowledge of sub-optimal performance of this APVMA registered vaccine to provide protection against the ‘conventional’ (Czech) strain of RHDV.

In mid-2015 a novel genotype (RHDV2) was detected in Australia and is now widely distributed. There are many reports of this genotype causing disease and death in vaccinated rabbits and so this is probably influencing public concern about the efficacy of vaccines for protection against RHDV1 strains.

As part of the strategy to alleviate concerns about protection of ‘non-target’ rabbits there is a concerted effort to remind the public about minimising the risk to their animals. This involves the use of vaccination and adoption of biosecurity practices.   

Vaccination

Review of the most recent RHDV chapter of the OIE Manual for diagnostic tests and vaccines for terrestrial animals (OIE, 2016) provides strong support for the statement that existing vaccines provide good protection against genotype 1 strains of RHDV (ie conventional and RHDVa variants). It states:

“Indirect control of the disease is easily achieved by vaccination. ….. Vaccinated animals quickly produce solid protective immunity against RHDV infection (within 7–10 days) and experimental data indicate that protection lasts for a long period (over 1 year). As RHDV2 is a distant antigenic subtype or even a second RHDV serotype, combined vaccination with both antigenic types or the use of a vaccine homologous to the RHDV strain identified during the epidemics or the outbreak, is highly advisable.”

Placing this into the Australian context, the existing registered vaccine, when used in accordance with the manufacturer’s instructions, is expected to provide good protection against the currently circulating strains that have arisen from the Czech strain released in 1996, as well as the Korean or RHDV1 K5 variant planned for national release in Autumn 2017. Nevertheless, it is acknowledged that there is an urgent need to progress the development of a new vaccine to provide protection against RHDV2 strains. Research is currently being undertaken by NSW DPI to meet this need.

Apart from field experience in Australia that supports the efficacy of the currently registered vaccine against Type 1 strains, there is comparable field experience from a number of Western European countries where commercial rabbit production occurs on a very large scale. Indeed, the vaccine currently used in Australia is produced in Europe. Consequently, the European experience is also relevant to Australia.

Finally, in reviewing field experience with the use of inactivated vaccines for protection against infection with RHDV, adverse comments need to be considered carefully because of the possibility that the vaccine has been mishandled or has not been used strictly in accordance with the manufacturer’s instructions. Factors that are relevant include extended inter-dose intervals, vaccination of very young animals with high levels of maternally derived antibody, and most significantly, administration of reduced doses of vaccine in order to reduce costs. It is known that use of reduced doses is a practice in some situations in Australia.

To further support the performance of vaccines against variant strains of RHDV1 (ie RHDVa), there are also some experimental investigations that are relevant. In Germany after the emergence of the RHDVa variants, rabbits that had been vaccinated with full and reduced doses of vaccine were challenged with ‘conventional’ and RHDVa strains 52 days post vaccination (Schirrmeir et. al., 1999). The vaccine provided full protection using either a full or ¼ dose but failed to protect rabbits given 1/16 dose. In a more recent review, the authors stated “inoculation of vaccinated rabbits with RHDVa isolates caused no death” (Abrantes et al., 2012).

Finally, there are two studies that have been undertaken in NSW at the Elizabeth Macarthur Agricultural Institute (EMAI) that are relevant. Vaccinated rabbits were challenged by oral administration of either the Czech strain of RHDV1 or the Korean (K5) RHDV1 strainStatistical analysis of this data (Analysis of deviance, generalised linear model with binomial distribution) shows a highly significant effect (P<0.0001) of vaccination on survival, with all vaccinated rabbits surviving to the end of the 7 day study, despite being given 10,000 rabbit infective doses of virus by direct oral administration – ie, 10,000 times more virus than is needed to kill one rabbit. At post-mortem examination, real time PCR assays demonstrated that there was no evidence of active virus replication in any of these rabbits. The control rabbits that were challenged orally all died  – 3 between 48-72 hours post administration and the fourth between 96-120 hours. This study has recently been submitted to the Australian Veterinary Journal for publication as a short communication (Read and Kirkland, 2017). Finally, rabbits that were vaccinated with one quarter of the recommended dose of vaccine were also challenged with 3 different doses of RHDV1 K5. Whether challenged with 10, 100 or 1000 rabbit infective doses, all vaccinated rabbits (6 or 7 per group) survived whereas all controls died.

In summary, there is no evidence in Australia or Europe that the current vaccine is ineffective against conventional (e.g. Czech strain) and RHDV1 (e.g. RHDV K5) strains.

Biosecurity measures

While vaccination will provide good protection against RHDV type 1 strains, rabbit owners are advised to implement a range of biosecurity measures. These not only help to reduce the risk of RHDV infection in sub-optimally vaccinated animals but also reduce the possibility of infection with other pathogens such as myxoma virus. Recommended measures include insect proofing, good hygiene practices and avoiding contact with other rabbits. The need for these measures has been provided in press releases to the general public, directly to the veterinary profession through the Veterinary Practitioners Board and is also listed on websites – for example:

Conclusions

  1. Taking into account all field and experimental data that is available, there is considered to be a substantial weight of evidence to support the efficacy of inactivated RHDV vaccines against both the Czech strain that has been circulating in Australia since 1996 and the new Korean or RHDV1 K5 strain, for which release is planned in March 2017.
  2. There is no field or experimental evidence to suggest that the currently available vaccine will not provide protection against the new RHDV1 K5 release strain
  3. There is a need to expedite production of a new RHDV vaccine to provide, at the least, protection against Type 2 strains of RHDV.

References

Abrantes, J., van der Loo, W., Le Pendu, J., Esteves, P.J., 2012. Rabbit haemorrhagic disease (RHD) and rabbit haemorrhagic disease virus (RHDV): a review. Veterinary Research 43:12-31.

OIE (Office of International des Epizooties) (2016). Chapter 2.6.2 Rabbit Haemorrhagic Disease, In: Terrestrial Manual of standards for diagnostic tests and vaccines. Office of International des Epizooties, Paris France, pp. 1-18. https://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.06.02_RHD.pdf

Read, A. J. and Kirkland, P.D. (2015). Evaluation of a commercial Rabbit Haemorrhagic Disease Virus vaccine against two strains of the virus. Final Report. Invasive Animal CRC.

Read, A.J. and Kirkland, P.D. (submitted). The efficacy of a commercial vaccine against different strains of rabbit haemorrhagic disease virus. Australian Veterinary Journal.

Schirrmeier, H., Reimann, I., Köllner, B., Granzow, H. (1999). Pathogenic, antigenic and molecular properties of rabbit haemorrhagic disease virus (RHDV) isolated from vaccinated rabbits: detection and characterization of antigenic variants. Archives of Virology 144, 719-735.

This technical note has been written by Veterinary virologists, P.D. Kirkland and A.J. Read – February 2017