Complete, Long-Lasting Protection against Lethal Infectious Bursal Disease Virus Challenge by a Single Vaccination with an Avian Herpesvirus Vector Expressing VP2 Antigens

Abstract

Marek's disease herpesvirus is a vaccine vector of great promise for chickens; however, complete protection against foreign infectious diseases has not been achieved. In this study, two herpesvirus of turkey recombinants (rHVTs) expressing large amounts of infectious bursal disease virus (IBDV) VP2 antigen under the control of a human cytomegalovirus (CMV) promoter or CMV/␤-actin chimera promoter (Pec promoter) (rHVT-cmvVP2 and rHVT-pecVP2) were constructed. rHVT-pecVP2, which expressed the VP2 antigen approximately four times more than did rHVT-cmvVP2 in vitro, induced complete protection against a lethal IBDV challenge in chickens, whereas rHVT-cmvVP2 induced 58% protection. All of the chickens vaccinated with rHVT-pecVP2 had a protective level of antibodies to the VP2 antigen at the time of challenge, whereas only 42 and 67% of chickens vaccinated with rHVT-cmvVP2 or the conventional live IBDV vaccine, respectively, had the antibodies. The antibody level of chickens vaccinated with rHVT-pecVP2 increased for 16 weeks, and the peak antibody level persisted throughout the experiment. The serum antibody titer at 30 weeks of age was about 20 or 65 times higher than that of chickens vaccinated with rHVT-cmvVP2 or the conventional live vaccine, respectively. rHVT-pecVP2, isolated consistently for 30 weeks from the vaccinated chickens, expressed the VP2 antigen after cultivation, and neither nucleotide mutations nor deletion in the VP2 gene was found. These results demonstrate that the amount of VP2 antigen expressed in the HVT vector was correlated with the vaccine efficacy against lethal IBDV challenge, and complete protective immunity that is likely to persist for the life of the chickens was induced. Marek's disease (MD) virus (MDV) is a cell-associated, lymphotropic alphaherpesvirus of chickens that causes the most-common, highly contagious T-cell lymphoma (6), and all three serotypes of MDV have been completely sequenced (1,19,22,41). The MDV vaccine strains, which are serotypes 1 (MDV1), MDV2, and MDV3 (herpesvirus of turkey [HVT]) (6), have merits as a distinguished vector (7,15,24,30). MDV vaccines can overcome the inhibition of maternal antibodies (28, 35) and might induce long-term protective immunity in chickens. Down-regulation of major histocompatibility complex class I expression is a common mechanism of herpesviruses, including MDV, used to evade cellular immunity and persist in their hosts (17,20). MDV1 has high vaccine efficacy against MD but grows slowly in cell culture, whereas HVT has a relatively low vaccine efficacy but is highly safe for chickens and grows remarkably well in cell culture. Despite the high potential of the MDV vectors, attempts to elicit complete protection against infections in chickens have not been successful (8, 13, 15, 27, 28, 31-33, 35, 39). The lack of effective MDV1 recombinants is likely due to a variety of factors such as the difficulty in making recombinants without attenuating the virus.Infectious bursal disease (IBD) virus (IBDV), a member of the Birnaviridae famil...

Infectious Bursal Disease: Pathogenicity and Immunogenicity of Vaccines

“…This suggests that the VP2 gene is efficiently expressed and that the translated transgenic protein maintained conformational native VP2 characteristics. Similar protection levels of SPF birds induced by another recombinant vaccine, also with the HVT vector, were previously reported (Tsukamoto et al, 2002).…”

The Hybrid Cytomegalovirus Enhancer/Chicken β-Actin Promoter along with Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element Enhances the Protective Efficacy of DNA Vaccines

“…Viral vectors encoding both elements show the greatest expression (38,39), indicating that both elements can act synergistically to boost the level of Ag. Earlier vaccination studies using DNA vaccines that include either CAG or WPRE have been performed and compared with conventional CMV vectors (37,40,41), and each has ascribed increased immune responses to increased Ag expression. In this study we describe for the first time the synergistic effects of both these elements in a single DNA vaccine.…”

Progress toward the development of polyvalent vaccination strategies against multiple viral infections in chickens using herpesvirus of turkeys as vector

“…Although we only monitored the duration of immune responses to 13 weeks, the results convincingly dictate that the higher levels of immunity produced by rHVT-H7HA should have persisted during the lifetime of the chicken, as was seen in HVT-based vaccines for MDV and IBDV. 24 …”

“…Such recombinant HVT-based vaccines confer excellent and long-lasting simultaneous protective immunity in chickens against more than one pathogen, following the "one stone, two birds" principle. [21][22][23][24] However, these HVT recombinants have been prepared using conventional genomic recombination techniques, which are extremely time-consuming and laborintensive. Additionally, it has never been possible to recover purified recombinant viruses through plaque selection methods, leading to decreased immunogenicity after continuous passage in cultured cells.…”