Nobivac^® Myxo-RHD PLUS Questions and Answers

Nobivac Myxo-RHD PLUS is a vectored vaccine, which provides 3 in 1 coverage against myxomatosis, classic and variant strains of Rabbit Haemorrhagic Disease (RHD), ensuring rabbits are immunised against both common strains of RHD.

An emerging variant strain of Rabbit Haemorrhagic Disease (RHD-2) was discovered in 2010 in France and has since become widespread in the UK. Further research and pharmacovigilance demonstrated that vaccination with classic (RHD-1) strains does not provide reliable immunity against the variant RHD-2 strains.

Nobivac Myxo-RHD PLUS includes two RHD-vectored myxoma strains to provide comprehensive immunity against myxomatosis, and both classic and variant RHD.

Nobivac Myxo-RHD PLUS provides broad cover against myxoma virus and both RHD-1 and RHD-2 from a single vaccine using the same recombinant vector technology present in Nobivac Myxo-RHD. The vaccine contains a similar amount of classic strain vector to Nobivac Myxo-RHD, ensuring no reduction of antigenicity against this component.

A convenient single dose given from 7 weeks of age provides protection against all 3 pathogens with a minimum duration of immunity of 12 months.

The vaccine has a number of advantages/benefits:

1.      Vaccinates against both field strains of RHD

- contains equal quantities of both myxoma-virus vectored classic RHD-1 and variant RHD-2 strains. Both strains use VP 60 capsid genes.

2.      No adjuvant is required as it is a live vectored vaccine

3.      Lower volume to administer compared to Nobivac Myxo-RHD

- reconstituted with 0.5 ml of vaccine solvent rather than 1 ml

4.      May be given from 5 weeks of age 

- however, to avoid a reduction duration of immunity caused by MDA in some rabbits, vaccination after 7 weeks of age is recommended

5.      Approved for use during pregnancy

Nobivac Myxo-RHD PLUS has proven efficacy in naïve rabbits and effectively boosts rabbits previously vaccinated against myxomatosis, RHDV-1 and RHDV-2. However please note that Nobivac Myxo-RHD PLUS vaccine product labelling also includes the following statement:

Rabbits that have been vaccinated previously with another myxomatosis vaccine, or that have experienced natural myxomatosis infection in the field, may not develop an adequate immune response against rabbit haemorrhagic disease following vaccination.

This statement relates to the phenomenon of vector interference which is very relevant to a very specific subset of rabbits being switched over to the new vaccine. Based on the results of efficacy and switching studies, an optimum approach to avoid this potential risk as laid out below. 

Annual boosters for all groups of rabbits in all subsequent years can be managed successfully with Nobivac Myxo-RHD PLUS.

No more Nobivac Myxo-RHD is being manufactured and stocks will run down during the year. We recommend that while stocks last that the legacy vaccine is reserved to dose rabbits that need to be given an inactivated RHDV-2 vaccine this year (please see switching advice above).

The onset of immunity following Nobivac Myxo-RHD PLUS is 3 weeks.

Whilst theoretically a rabbit's immune system will have been primed if it has received an RHDV-2 vaccine at any time point, we do not have data that determines the impact of vaccination with Nobivac Myxo-RHD PLUS in rabbits kept up to date with Nobivac Myxo-RHD but at extended intervals from their previous RHDV-2 vaccine. We would suggest that the RHDV-2 vaccine ideally needs to be current (i.e. within the last 12 months) otherwise we should treat this individual as a group 3 rabbit and vaccinate again with an inactivated product.

The safety profile is very similar to the current Nobivac Myxo-RHD product. The listed adverse reactions are:

A transient temperature increase of 1 – 2 °C can commonly occur. A small, non-painful swelling (maximum 2 cm diameter) at the injection site is commonly observed within the first two weeks after vaccination. The swelling will resolve completely by 3 weeks after vaccination. In pet rabbits, local reactions at the injection site such as necrosis, scabs, crusts or hair loss may occur in very rare cases. Serious hypersensitivity reactions, which may be fatal, may occur after vaccination in very rare cases. The appearance of mild clinical signs of myxomatosis may occur within 3 weeks of vaccination in very rare cases. Recent or latent infection with field myxoma virus seems to play a role in this to a certain extent.

The frequency of adverse reactions is defined using the following convention:

• very common (more than 1 in 10 animals treated displaying adverse reaction(s))
• common (more than 1 but less than 10 animals in 100 animals treated)
• uncommon (more than 1 but less than 10 animals in 1,000 animals treated)
• rare (more than 1 but less than 10 animals in 10,000 animals treated)
• very rare (less than 1 animal in 10,000 animals treated, including isolated reports)

This statement refers to a phenomenon known as vector interference. In the case of Nobivac Myxo-RHD, the vector virus is an attenuated myxoma virus strain which is modified by inclusion of a nucleic acid sequence which codes for the RHDV capsid protein and the removal of virulence factors.

Within Nobivac Myxo-RHD PLUS there are two vector constructs, one with the capsid sequence from RHDV-1 and a second from RHDV-2. Replication of these viruses within cells will therefore induce humoral and cell-mediated immunity to myxomatosis, RHDV-1 and RHDV-2.

Vector interference occurs when the level of pre-existing immunity to the vector virus is sufficient to limit the level of vaccine virus replication, preventing adequate expression of vectored antigens to stimulate priming immunity. Typically, this has been observed when using a novel myxoma-vectored RHD vaccine when there is already strong immunity to myxomatosis induced by previous vaccination (or potentially by field challenge) i.e. as occurred when Nobivac Myxo was superceded by Nobivac Myxo-RHD. In such an instance, if immunity against RHD has not already been primed, an effective RHD response may be blocked.

Once Nobivac Myxo-RHD has left the market, and all rabbits receive the new vaccine the priming issue associated with previous myxomatosis vaccination should no longer be a problem and a single vaccine will suffice.

Nobivac Myxo-RHD PLUS is a single dose vaccine so a single dose should immunise at any stage, however immunity has only been assessed up to 12 months. The licensed minimum duration of immunity is 12 months.

Within our 12 month duration of immunity studies, a few pox-like lesions on face or ears were seen, and provided these are very localised we feel these can be consistent with the expected immunity. Since 2011, in the majority of cases where myxomas are seen in the first three weeks post vaccination with Nobivac Myxo-RHD, we can demonstrate co-infection of the pet rabbit with both the vaccine strain (exposure during vaccination) and a field strain of myxoma virus. In studies, field strains appear to be able to form distinct but limited lesions on newly vaccinated rabbits whilst vaccinal protection is still developing.

You could consider lapsed rabbits as naïve but we have only assessed vector interference up to 12 months and only 25% of rabbits at 12 months post vaccination were primed to RHDV-2. The issue is we do not know how long it would be before residual immunity would dissipate enough to get 100% of rabbits to prime their immunity to RHDV-2. On this basis it is safest to assume that Nobivac Myxo-RHD lapsed rabbits are vaccinated and to future vaccinate as per the protocol for Group 3 rabbits. Of course, if it is only Nobivac Myxo-RHD that has lapsed and they are up to date for RHDV-2 then these rabbits can simply move to Nobivac Myxo-RHD PLUS.

We would not expect a concern regarding boostering the Nobivac Myxo-RHD at a shorter interval and therefore the new Nobivac Myxo-RHD PLUS can be administered in this scenario, provided an inactivated RHDV-2 vaccine was given in the last 12 months.

No, the minimum age is determined by the age rather than the weight for vaccines. Safety trials for the vector virus were conducted in Netherland dwarfs for Nobivac Myxo-RHD, and these studies are appropriate to the new vaccine since formulation-wise the two products are similar enough to inform on safety.

You will need to synchronise around the booster timing of either myxoma virus or RHDV-2. The attending vet can make the decision, but it may be most efficient to switch sooner rather than later.

This depends if the rabbit has had an inactivated RHDV-2 vaccine. If it has, then the rabbit can receive Nobivac Myxo-RHD PLUS this year, if the rabbit hasn’t then it will require an inactivated RHDV-2 vaccine as soon as possible. If Nobivac Myxo-RHD is due around this time, this can be given around 2 weeks before or after the inactivated RHDV-2 vaccine. If stocks of Nobivac Myxo-RHD are not available by the time this rabbit requires a myxomatosis vaccine, the new product, Nobivac Myxo-RHD PLUS can be given at this time.

From 7 weeks for the full duration of immunity for 12 months. It can be used from 5 weeks old if an individual requires earlier protection, however you would need to repeat the vaccine at 7 weeks old in order to get the full duration of immunity.