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Dynamics of productive replication of Marek's disease virus given by revaccination

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Changxin Wu1
Jinjiao1
Junji Gan1
Ping Liang1
Xufen Lui1
Fred Davison2

1Lab. of Animal Infectious Disease, Vet School, Yangzhou University, Yangzhou, China
2Avian Immunology Group, Institute for Animal Health, Compton, Newbury, UK

Marek's disease (MD) is a herpesvirus-induced lymphomatous disease in chickens and it is one of the most fascinating herpetic disorders because infection of susceptible chickens results the rapid formation of T-cell lymphopmas that are preventable by vaccination.
The introduction of successful MD vaccination has been a singular achievement for both agricultural development and as a model system for studying cancer prevention in a natural host. However, since the application of global MD vaccination, more virulent Marek's disease viruses (MDV) have emerged and some of them can break though vaccinal protection, such as very virulent MDV (vvMDV) and very virulent plus MDV (vv+MDV).
In some countries or areas MD vaccine failures become common, again causing huge economic losses and becoming a serious problem in poultry. Since the end of 1980's some countries, with high frequencies of MD vaccine failures, have introduced a strategy of using re-vaccination to control MD, and empirical evidence from the field practice provides increasing support for use of revaccination with MD disease vaccines, a practice that has become common in many countries.
The mechanism of improvement protection against MD by revaccination is not known yet. One main point of our hypothesis is that immune system is more competent at day seven old, or older ages, and of course revaccinated chicken can generate stronger immunity to MD.
Another main point of our hypothesis is that revaccinated MD vaccine virus also has productive infection and latent infection which both have been confirmed to happen in single vaccination of MD vaccines.
After inoculation of MDV, MDV has a period of about two weeks productive infection and then enter latent infection for life. Productive infection can produce MDV antigens and latent infective can not produce any MDV antigen at all, we considered that the productive infection of revaccinated virus is very crucial for improving immunity to MD as it can produce more MDV antigens which can stimulate immune system again and activate its specific immune memory.
It is not known if the productive infection of revaccinated vaccine virus replicates after revaccination and how it affects immunity to MD.
This study is to determine if the productive infection of revaccinated vaccine virus exists or not and the dynamics of productive replication of MD vaccine virus given by revaccination in comparison with the replication of MD vaccine virus given revaccinated virus given by single vaccination.
An experiment was conducted to investigate the dynamics of productive replication of MD vaccine virus given by revaccination in comparison with the replication of MD vaccine virus given as a single vaccination.
Six groups of specific pathogen free (SFP) white Leghorn chickens were vaccinated with various combinations of herpesvirus of turkey (HVT, strain Fc126), and attenuated serotype I strain, CVI988, at day 1 or day 7 old and revaccinated at day 7 old.
Three chickens of each group of five chickens were randomly bled at three or four day's intervals after vaccination or revaccination. Peripheral leukocytes (PBL) were isolated from blood samples and then were analysed by the flow cytometry using monoclonal antibodies specific to MDV serotype 3 or MDV serotype 1 to identify reproductively infected cells.
To determine if revaccination affected the replication of very virulent Marek's disease virus (vvMDV), at 25 days age when Peripheral leukocytes productively infected with vaccine virus were not detectable by flow cytometry. All PBL samples were also prepared every three or four days after challenge with RB1B.
The results given by flow cytometry analysis indicated that numbers of productive-infected PBL reach a peach on day after HVT virus was inoculated at either 1 or 7 days of ages, with two peaks at day 7 and day 14 in revaccination group (Figure 1). After challenge of very virulent MDV strain RB1B, the dynamics of the challenged MDV is different between single vaccination groups and revaccination groups, the peaks of replication of RB1B in revaccination groups are lower than those in single vaccination groups.

articoli/2007/VTR_2007_01a/VTR_2007_01a_G1.gif

These results suggest that the productive replication of the vaccine virus given by revaccination exactly exists and could play an important role in augmenting immunity to MD.
From this study revaccinated MD vaccine virus exactly has its own productive replication which produces MDV antigen to stimulate chicken's immune system, and these antigens also activate its specific memory immune responses, therefore chicken has stronger immunity to MD. One other hand, the secondary vaccination is carried out at the older age stage, chicken immune system has become more competent so revaccinated MDV may produce stronger immunity to MD.
One more thing is that commercial chicken has maternal antibody to MDV and at old stage the maternal antibody levels should decline. Considered three effectors above, revaccinated chicken can be better protected from MD. To completely confirm our hypothesis scientific more experiments are needed.

From Proceedings of the "7th International Symposium on Marek's disease", St. Catherine's College, Oxford, United Kingdom.

 

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