Vaccination against RHD

Development of vaccines against RHD

Due to the devastating effects of RHD in China, a vaccine was quickly developed. It was produced from inactivated virus obtained from the liver and spleen of infected rabbits. Live rabbits are needed to cultivate the RHD calicivirus because it cannot be grown in tissue culture. Inactivated adjuvanted vaccines against RHD (e.g. Cylap and Lapinject) became available in other countries. These vaccines protected rabbits against RHDV1 although they had the potential to cause tissue reactions at the inoculation site and they also posed a risk to the person administering the vaccine if accidental self-inoculation occurred. The reaction was due to the adjuvant in the vaccine and not the virus.

In 2012, a bivalent vaccine against both myxomatosis and RHD came on the market. (Nobivac Myxo-RHD, MSD Animal Health). This vaccine was manufactured differently from previous vaccines against RHD. It is made from a recombinant virus constructed by inserting the RHDV capsid gene into the myxoma virus genome (Spibey et al. 2012). The technology used to produce this vaccine allows the RHD component to be produced in vitro instead of using live rabbits for virus cultivation. In the UK and other countries, this vaccine quickly superseded because it protected against both myxomatosis and RHD with a single annual injection.

In 2014, RHDV2 spread into UK. By 2016, it had reached epidemic proportions (Harcourt-Brown et al. 2020) and it was becoming obvious that Nobivac Myxo-RHD was not protecting rabbits from RHDV2. Inactivated adjuvanted vaccines against RHDV2 had been developed in other countries where rabbit meat is popular and were imported into UK. Two vaccines subsequently obtained product licences in UK: Filavac VHD K C+V (Ceva Animal Health) and Eravac (Hipra Laboratories).

On May 1st, 2020, Nobivac Myxo-RHD Plus became available in UK and Europe. This vaccine is manufactured from a recombinant myxomavirus containing genetic material from both RHDV1 and RHDV2 viruses.

Comparison of vaccines available in UK (May 2020)

    

Vaccine

name

Nobivac Myxo-RHD

Filavac

Eravac

Nobivac Myxo-RHD plus

Effective against RHDV1

Yes

Yes

No

Yes

Effective against RHDV2

No

Yes

Yes

Yes

Inactivated adjuvanted vaccine

 

Yes

Yes

 

Recombinant vaccine

Yes

 

 

Yes

Earliest age for vaccination

5 weeks

10 weeks 

30 days

5 weeks in rabbits with no maternal immunity.

7 weeks in rabbits

To ensure the full duration of immunity, vaccination from 7 weeks of age is advised in this case.

Onset of immunity

3 weeks

7 days

7 days

3 weeks

Duration of immunity

1 year

1 year

1 year

1 year

Further information

No longer manufactured. Replaced by Nobivac Myxo-RHD Plus

Manufacturers say rabbits as young as 4 weeks may be vaccinated effectively but another dose is required after 10 weeks of age to confer enough immunity to last for one year

 

Rabbits that have been exposed to myxomatosis may not develop an adequate immune response against RHD following vaccination.

Factors to consider when choosing a vaccine

  • Although RHDV2 has superseded RHDV1 in many parts of the world, vaccination against both RHDV1 and RHDV2 is recommended for pet rabbits because RHDV1 may be present in the wild rabbit population and is still a threat.
  • RHDV2 is endemic in the wild rabbit population and rabbits that are unvaccinated or are overdue for vaccination are susceptible. For these rabbits, the interval between administering a vaccine and the onset of immunity is important. Inactivated adjuvanted vaccines (Filavac, Eravac) take 7 days to become effective in comparison with Nobivac Myxo-RHD Plus, which takes 3 weeks.
  • In the face of a suspect outbreak of RHD, immediate vaccination of in-contact rabbits with Filavac gives the best chance of protection. Although RHDV2 is fare more likely than RHDV1, PCR testing is necessary to confirm the genotype and may take a few days. Eravac is only effective against RHDV2.
  • Recombinant vaccines (Nobivac Myxo-RHD and Nobivac Myxo-RHD Plus) are made from attenuated myxomavirus. Antibodies to myxomatosis in rabbits that have been exposed to the disease could interfere with the vaccine, so it is not effective against RHD. This is important in pet rabbits that might have contact with wild rabbits or insect vectors during an outbreak of myxomatosis. There is no interference between myxomatosis and RHD vaccination with inactivated adjuvanted vaccines.
  • Some owners have ethical objections to inactivated adjuvanted vaccines because rabbits are used to produce the vaccine.
  • Nobivac Myxo-RHD Plus is a new vaccine. Its efficacy in naturally occurring outbreaks is unknown at the present time (May 2020).
  • Inactivated adjuvanted vaccines were effective in protecting pet rabbits during a naturally occurring outbreak of RHDV2 in UK (Harcourt-Brown et al. 2020- in press) although there were some failures.

Some reasons for vaccine failure

Although it is easy to blame a vaccine when a vaccinated rabbit dies from RHD, there are several possible explanations for vaccine failure. Many of these are overcome if the rabbit is vaccinated by a veterinary surgeon or veterinary nurse after a health check.

  • Transport conditions: Vaccines need to be kept at the correct temperature. They are refrigerated at a specific temperature during shipping from the manufacturers to the wholesalers and subsequent transport to veterinary practices. Vaccines that are not transported at the correct temperature may not be as effective.
  • Incorrect storage of vaccine: Veterinary surgeries have to comply with stringent regulations about storage of vaccines. The vaccine has to be kept refrigerated at the correct temperature and records are kept of temperature measurements in fridges that contain vaccine. These requirements may not be met by owners or breeders that store vaccine in their fridge.
  • Incorrect administration: Rabbit skin is thin. It is easy for a needle to penetrate two layers of skin that is tented up to insert a needle into. This means the vaccine is not injected into the subcutaneous space but is squirted on to the skin instead. This is less to happen if a veterinary surgeon or veterinary nurse administers the vaccine. If it does happen, another vaccine needs to be administered.
  • Using up multidose vials: Vaccines against RHD are available as multidose vials. These are intended for use within hours once the vial is opened or the vaccine mixed with diluent. Vaccines are not cheap and there is a temptation to store opened vials and use them later. This will affect the efficacy of the vaccine. Vaccines administered at a veterinary practice are generally from single dose vials unless vaccination clinics are organised in which multidose vials are used. Unused vaccine from these clinics is disposed of according to the regulations covering the proper disposal of medication.
  • Underlying disease: The vaccine datasheets say that only healthy rabbits should be vaccinated. This is not because rabbits with underlying disease are at risk from the vaccine, but because the vaccine is less likely to be fully effective. Rabbits with underlying health problems may be immunologically compromised so they do not respond fully to a vaccination. Rabbits hide disease so it can be difficult to know if subclinical disease is present.
  • Already incubating the disease: Rabbits are often vaccinated against RHDV2 when other rabbits in the household have died suddenly. If the cause of death was RHDV2, then all the rabbits in the household will have been exposed and could be incubating the disease at the time of vaccination.
  • The rabbit was not vaccinated in the first place: This scenario is unlikely in pet rabbits. Rabbits that have been vaccinated should come with a vaccination certificate with the name, date and batch number of the vaccine they were given. If a vaccination certificate is not available, the safest option is to administer another vaccine
  • Individual variation: No vaccine is 100% effective. There are always individuals that do not respond to vaccination.

In commercial rabbits where hundreds of rabbits are vaccinated, it is possible to miss some individuals, or they may not have responded properly to the vaccine because of underlying disease or problems with administration. This was a reason for the recommendation for 6 monthly intervals between vaccination in meat rabbits by some vaccine manufacturers. This recommendation does not apply to rabbits kept as pets.