Page 367 - Avian Virology: Current Research and Future Trends

358 | Lupiani et al.

which makes differential diagnosis of poultry lymphomas chal- HVT vaccines
lenging. Histological examination of lymphomas followed by HVT were first isolated from turkeys by Anderson and Kawa-
confirmation by immuno-histological markers for T-cells and mura (Kawamura et al., 1969) and Witter (Witter et al., 1970).
Meq expression aids in differential diagnosis (Gimeno et al., Since these were naturally non-oncogenic viruses with homology
2005a). However, these assays are time consuming and MDV to pathogenic MDV-1, they were used as vaccines (Okazaki et
quantification by real-time PCR is now considered as an effi- al., 1970). HVT is the most widely used vaccine to control MD
cient alternative. Previous reports demonstrated that samples and is commonly used in broilers as a monovalent vaccine or as
from solid tumours, feather pulp (FP), and peripheral blood are part of a polyvalent vaccine in breeders and layers (Dunn and
all valid for detection and quantification of MDV viral load as Gimeno, 2013). Like all other MDV serotypes, HVT is a highly
a criterion for MDV diagnosis (Cortes et al., 2009). However, cell-associated virus and, as a consequence, vaccine prepara-
®
Flinders Technology Associates (FTA) cards can be used and tions require special handling and storage. However, unlike the
are a simpler method for the collection and shipping of DNA MDV-2 and MDV-1 viruses, it is possible to make cell free vaccine
samples for MD diagnosis with real-time PCR and monitor- preparation by sonication of HVT infected cell cultures (Calnek
ing MD vaccination (Cortes et al., 2009). Studies have showed et al., 1970b). Although these cell free preparations are easier to
that viral DNA from the FP and blood can be used for MD transport and handle, they are susceptible to neutralization by
diagnosis, while FP samples are better than blood samples for maternal antibodies thus are less efficient than cell associated
monitoring MD vaccination (Cortes et al., 2011). HVT vaccines (Prasad, 1978; Witter and Burmester, 1979), and
as a result, their use is restricted to small backyard flocks or coun-
tries where liquid nitrogen transportation is not practical.
MDV vaccines
Control of MD is primarily through vaccination using live vac- Recombinant vaccines
cines derived from all three MDV serotypes. Vaccines have been Several recombinant vaccines have been developed from all
successful at protecting chickens against MD induced tumours MDV serotypes, but only a limited number have been commer-
and mortality; but vaccinated chickens support replication and cialized. As MD vaccines require special storage and handling,
shedding of virulent field viruses. The widespread use of MD vac- early attempts to overcome this hurdle focused on the develop-
cines is thought to have contributed to the evolution of MDV field ment of fowlpox virus (FPV) as a vector for delivery of MDV
viruses towards greater virulence (Witter et al., 1997; Gandon et immunogenic antigens. Although FPV vectored vaccines showed
al., 2001; Davison and Nair, 2005; Gimeno, 2008). significant protection under laboratory conditions, they are not
commercially viable because of the presence of neutralizing
MDV-1 vaccines antibodies to FPV in commercial flocks resulting in limited
The first MD vaccine, HPRS-16/att, was generated by serial pas- protection. DNA vaccines were also developed to overcome this
sage of a virulent MDV in chicken kidney cells and was shown problem associated with transportation, but conferred limited
to provide protective immunity against virulent MD viruses protection (Tischer et al., 2002). Several attempts have also been
(Churchill et al., 1969). This vaccine was only used for a few years made to develop attenuated strains by deletion of genes involved
and was soon replaced by HVT that had a better safety profile. in pathogenesis. Deletion of meq resulted in fully attenuated
The CVI988 or Rispens is the most efficacious vaccine currently viruses with regards to oncogenicity, while maintaining a normal
available. It was isolated in the Netherlands and showed low level early cytolytic replication, and proved to be an effective vaccine
of oncogenicity (Bülow, 1977), but was attenuated by serial cell candidate under both laboratory and field conditions (Lee et al.,
culture passage. After the emergence of vv and vv+ MDV field 2008, 2010). However, Meq deleted virus resulted in lymphoid
strains, CVI988 became the vaccine of choice worldwide because organ atrophy and body weight reduction in highly susceptible
of superior protection (Witter et al., 1995) and is now considered MDV maternal antibody negative chickens (Dunn and Silva,
the ‘gold standard’ of MD vaccines. 2012; Lee et al., 2012), thus are not commercially available.
More recently, a novel vaccine called CVRM was developed by
MDV-2 vaccines inserting the LTR sequences of REV into CVI988 (currently used
Several research groups in Europe (Biggs, 1972) and in the US vaccine). This novel vaccine had increased in vitro replication,
(Schat and Calnek, 1978) have isolated other naturally avirulent compared with CVI988, did not induce lymphoid organ atrophy,
viruses from healthy chickens. These viruses were serologically and showed protection indices equal or superior to CVI988
distinct from pathogenic MDV-1 and apathogenic in chickens (Lupiani et al., 2013).
and were classified as novel serotype 2 viruses (Bulow and Biggs,
1975a,b). Serotype 2 vaccines provide limited protection against MDV as vaccine vector
vv MDV viruses, but their protection is enhanced when admin- The long-term protection conferred by MD vaccines, and their
istered in combination with other serotypes (Witter and Lee, ability to overcome maternal antibodies, has made MDV an
1984). This protective synergism has been shown to be specific excellent candidate vector to protect not only against MD but
for MDV-2 and HVT combinations, but not for MDV-1 and also against other important viral poultry diseases. Both HVT
MDV-2 and as a consequence, MDV-2 viruses are generally used and MDV-1 have been exploited for use as vector vaccines to
in bivalent or trivalent vaccine formulations. deliver immunogenic genes from Newcastle disease virus (NDV)