1990. lymphocyte proliferative activity; and higher levels of neutralizing antibody than single vaccination. These findings disagree with the postulate that MDV antigens persist, stimulate the immune system, and maintain a high level immunity after vaccination. The suppression of productive contamination by maternal antibodies in chickens receiving the primary vaccination and a lower level of productive contamination in the revaccination groups challenged with MDV were observed. The information obtained in this study suggests that the productive contamination with revaccinated MDV in chickens plays a crucial role in the induction of superior immunity. This obtaining may be exploited for the development of a novel MD vaccine that results in the persistence of the CW-069 antigen supply and that maintains a high level of immunity and may also have implications for other viral oncogenic diseases in humans and animals. Herpesviruses are important pathogens associated with a wide range of diseases in human and animals. Marek’s disease (MD) is an important, ubiquitous, contagious, CW-069 and oncogenic disease in chickens caused by Marek’s disease computer virus (MDV), an alphaherpesvirus (12). Apart from its importance in the poultry industry and for animal welfare (5), MD makes a significant contribution to our understanding of herpesvirus-associated oncogenicity due to the many MD lymphomas with a biological nature similar to that of the lymphoid neoplasia associated with human herpesviruses, such as Epstein-Barr computer virus (17). Studies have suggested that MD is usually a natural CW-069 model for lymphomas that overexpress the Hodgkin’s disease antigen, CD30 (7), and MD in small animals provides a well-defined model of general tumorigenesis and virus-induced lymphomagenesis (5, 7, 12, 17, 22). Unlike human diseases caused by herpesviruses, MD is the first lymphoproliferative disease which is usually effectively controlled and prevented by a vaccination strategy. The introduction of successful MD vaccines derived from either attenuated serotype 1 MDV (MDV1) (16), avirulent MDV1 (29, 30), or MDV2 or MDV3 (herpesvirus of turkeys [HVT]) (24) has been a singular achievement both for agricultural development and as a model system for studying the prevention of malignancy in the natural host. Thus, research around the pathogenesis and immunology of MD has significant importance for comparative medicine in humans and animals. A variety of vaccines and vaccination procedures are practically applied for the effective control and prevention of MD in the field (39). However, since the application of global MD vaccination 30 years ago, oncogenic MDV constantly trends toward increasing virulence, and more virulent MDV strains have emerged. Some of these can break through Rabbit Polyclonal to DIDO1 vaccinal protection, such as very virulent MDV (vvMDV) and very-virulent-plus MDV (vv+MDV), which seriously threaten the effectiveness of the existing MD CW-069 vaccines (16, 22, 24, 29, 30, 39). In some countries or areas, MD vaccine failures caused by vvMDV have become common again, causing huge economic losses, and this is becoming a serious problem in poultry. Given the tendency for MDV to increase in virulence and the economic pressures confronting the poultry industry in some parts of the world (39), it is not realistic to await the arrival of more effective MD vaccines superior to the current gold standard vaccine, CVI988. Since the end of the 1980s, in order to deal with this problem by improving the protective efficacy of the vaccine to reduce the incidence of MD, some countries with high frequencies of MD vaccine failures have introduced a revaccination CW-069 strategy (39). The common regimens of revaccination are priming of 1-day-old chickens and boosting them at either day 7 or day 14. Statistically, revaccination provides better protection than single vaccination in the field (41). Even though the MD revaccination strategy has become common practice in some regions of countries with serious problems with MD, the mechanisms by which superior immunity is usually induced by revaccination have not been explored through the use of laboratory experiments. We generated a hypothesis around the mechanisms by which revaccination against MD provides enhanced immunity. The hypothesis consists of three main points, including factors related to both the vaccine virus and the immunized host: (i) chickens revaccinated with MDV experience a.