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Shigeo Yamaguchi - One of the best experts on this subject based on the ideXlab platform.

  • complete long lasting protection against lethal infectious bursal disease virus challenge by a single vaccination with an avian Herpesvirus Vector expressing vp2 antigens
    Journal of Virology, 2002
    Co-Authors: Kenji Tsukamoto, S Saito, S Saeki, T Sato, Nobuhiko Tanimura, T Isobe, Masaji Mase, Tadao Imada, N Yuasa, Shigeo Yamaguchi
    Abstract:

    Replication-competent Herpesvirus Vectors are prospective vaccine vehicles for animals for the following reasons. (i) The Vectored vaccines are of the safe subunit type and express multiple antigens. (ii) Both humoral and cellular immune responses against pathogens can be induced in animals. (iii) They have a potential for long-term induction of protective immunity against pathogens in animals. 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 family, causes considerable economic losses in the poultry industry by inducing bursal destruction, immunosuppression, and high mortality in young chickens (21, 23, 42). Although live IBDV vaccines are highly efficacious (18), the vaccine efficacy decreases in the presence of maternal antibodies (23, 38, 42), and some of them cause bursal atrophy (25). Highly efficacious and safe IBD vaccines are needed. The VP2 protein is the conformational protective antigen: VP2 or the neutralizing antibodies can elicit complete protection against a lethal IBDV challenge (2, 4, 9, 10, 14, 23). We previously developed a recombinant MDV (rMDV) expressing VP2 antigen under control of the simian virus 40 (SV40) early promoter and showed that it was safe for chickens. However, the efficacy was partial and did not persist for a long time (39, 40). Recombinant HVT (rHVT) expressing the VP2 antigen under the control of a cytomegalovirus (CMV) promoter also induced partial protection in chickens when one dose was used (8). Further studies are required to improve the vaccine efficacy of MDV-Vectored vaccines. In order to determine the association between the amounts of antigen expressed in an HVT Herpesvirus Vector and the vaccine efficacy, we developed two rHVTs expressing different amounts of IBDV VP2 antigens under the control of CMV or Pec promoters. The Pec promoter is a new promoter consisting of a CMV enhancer and a β-actin promoter and has promoter activity in chicken embryo fibroblasts (CEFs) approximately three times stronger than that of the CMV promoter (M. Kubomura, A. Fujisawa, T. Okuda, S. Saitoh, and A. Yasuda, unpublished data). The present study indicated that the amount of antigen expressed in the HVT Herpesvirus Vector was correlated with the vaccine efficacy against IBD. The rHVT expressing larger amounts of VP2 antigen conferred complete protection against the lethal IBDV challenge, which was expected to persist for the lifetime of the chickens.

  • complete long lasting protection against lethal infectious bursal disease virus challenge by a single vaccination with an avian Herpesvirus Vector expressing vp2 antigens
    Journal of Virology, 2002
    Co-Authors: Kenji Tsukamoto, S Saito, S Saeki, T Sato, Nobuhiko Tanimura, T Isobe, Masaji Mase, Tadao Imada, N Yuasa, Shigeo Yamaguchi
    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/beta-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.

Kenji Tsukamoto - One of the best experts on this subject based on the ideXlab platform.

  • complete long lasting protection against lethal infectious bursal disease virus challenge by a single vaccination with an avian Herpesvirus Vector expressing vp2 antigens
    Journal of Virology, 2002
    Co-Authors: Kenji Tsukamoto, S Saito, S Saeki, T Sato, Nobuhiko Tanimura, T Isobe, Masaji Mase, Tadao Imada, N Yuasa, Shigeo Yamaguchi
    Abstract:

    Replication-competent Herpesvirus Vectors are prospective vaccine vehicles for animals for the following reasons. (i) The Vectored vaccines are of the safe subunit type and express multiple antigens. (ii) Both humoral and cellular immune responses against pathogens can be induced in animals. (iii) They have a potential for long-term induction of protective immunity against pathogens in animals. 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 family, causes considerable economic losses in the poultry industry by inducing bursal destruction, immunosuppression, and high mortality in young chickens (21, 23, 42). Although live IBDV vaccines are highly efficacious (18), the vaccine efficacy decreases in the presence of maternal antibodies (23, 38, 42), and some of them cause bursal atrophy (25). Highly efficacious and safe IBD vaccines are needed. The VP2 protein is the conformational protective antigen: VP2 or the neutralizing antibodies can elicit complete protection against a lethal IBDV challenge (2, 4, 9, 10, 14, 23). We previously developed a recombinant MDV (rMDV) expressing VP2 antigen under control of the simian virus 40 (SV40) early promoter and showed that it was safe for chickens. However, the efficacy was partial and did not persist for a long time (39, 40). Recombinant HVT (rHVT) expressing the VP2 antigen under the control of a cytomegalovirus (CMV) promoter also induced partial protection in chickens when one dose was used (8). Further studies are required to improve the vaccine efficacy of MDV-Vectored vaccines. In order to determine the association between the amounts of antigen expressed in an HVT Herpesvirus Vector and the vaccine efficacy, we developed two rHVTs expressing different amounts of IBDV VP2 antigens under the control of CMV or Pec promoters. The Pec promoter is a new promoter consisting of a CMV enhancer and a β-actin promoter and has promoter activity in chicken embryo fibroblasts (CEFs) approximately three times stronger than that of the CMV promoter (M. Kubomura, A. Fujisawa, T. Okuda, S. Saitoh, and A. Yasuda, unpublished data). The present study indicated that the amount of antigen expressed in the HVT Herpesvirus Vector was correlated with the vaccine efficacy against IBD. The rHVT expressing larger amounts of VP2 antigen conferred complete protection against the lethal IBDV challenge, which was expected to persist for the lifetime of the chickens.

  • complete long lasting protection against lethal infectious bursal disease virus challenge by a single vaccination with an avian Herpesvirus Vector expressing vp2 antigens
    Journal of Virology, 2002
    Co-Authors: Kenji Tsukamoto, S Saito, S Saeki, T Sato, Nobuhiko Tanimura, T Isobe, Masaji Mase, Tadao Imada, N Yuasa, Shigeo Yamaguchi
    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/beta-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.

T Isobe - One of the best experts on this subject based on the ideXlab platform.

  • complete long lasting protection against lethal infectious bursal disease virus challenge by a single vaccination with an avian Herpesvirus Vector expressing vp2 antigens
    Journal of Virology, 2002
    Co-Authors: Kenji Tsukamoto, S Saito, S Saeki, T Sato, Nobuhiko Tanimura, T Isobe, Masaji Mase, Tadao Imada, N Yuasa, Shigeo Yamaguchi
    Abstract:

    Replication-competent Herpesvirus Vectors are prospective vaccine vehicles for animals for the following reasons. (i) The Vectored vaccines are of the safe subunit type and express multiple antigens. (ii) Both humoral and cellular immune responses against pathogens can be induced in animals. (iii) They have a potential for long-term induction of protective immunity against pathogens in animals. 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 family, causes considerable economic losses in the poultry industry by inducing bursal destruction, immunosuppression, and high mortality in young chickens (21, 23, 42). Although live IBDV vaccines are highly efficacious (18), the vaccine efficacy decreases in the presence of maternal antibodies (23, 38, 42), and some of them cause bursal atrophy (25). Highly efficacious and safe IBD vaccines are needed. The VP2 protein is the conformational protective antigen: VP2 or the neutralizing antibodies can elicit complete protection against a lethal IBDV challenge (2, 4, 9, 10, 14, 23). We previously developed a recombinant MDV (rMDV) expressing VP2 antigen under control of the simian virus 40 (SV40) early promoter and showed that it was safe for chickens. However, the efficacy was partial and did not persist for a long time (39, 40). Recombinant HVT (rHVT) expressing the VP2 antigen under the control of a cytomegalovirus (CMV) promoter also induced partial protection in chickens when one dose was used (8). Further studies are required to improve the vaccine efficacy of MDV-Vectored vaccines. In order to determine the association between the amounts of antigen expressed in an HVT Herpesvirus Vector and the vaccine efficacy, we developed two rHVTs expressing different amounts of IBDV VP2 antigens under the control of CMV or Pec promoters. The Pec promoter is a new promoter consisting of a CMV enhancer and a β-actin promoter and has promoter activity in chicken embryo fibroblasts (CEFs) approximately three times stronger than that of the CMV promoter (M. Kubomura, A. Fujisawa, T. Okuda, S. Saitoh, and A. Yasuda, unpublished data). The present study indicated that the amount of antigen expressed in the HVT Herpesvirus Vector was correlated with the vaccine efficacy against IBD. The rHVT expressing larger amounts of VP2 antigen conferred complete protection against the lethal IBDV challenge, which was expected to persist for the lifetime of the chickens.

  • complete long lasting protection against lethal infectious bursal disease virus challenge by a single vaccination with an avian Herpesvirus Vector expressing vp2 antigens
    Journal of Virology, 2002
    Co-Authors: Kenji Tsukamoto, S Saito, S Saeki, T Sato, Nobuhiko Tanimura, T Isobe, Masaji Mase, Tadao Imada, N Yuasa, Shigeo Yamaguchi
    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/beta-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.

T Sato - One of the best experts on this subject based on the ideXlab platform.

  • complete long lasting protection against lethal infectious bursal disease virus challenge by a single vaccination with an avian Herpesvirus Vector expressing vp2 antigens
    Journal of Virology, 2002
    Co-Authors: Kenji Tsukamoto, S Saito, S Saeki, T Sato, Nobuhiko Tanimura, T Isobe, Masaji Mase, Tadao Imada, N Yuasa, Shigeo Yamaguchi
    Abstract:

    Replication-competent Herpesvirus Vectors are prospective vaccine vehicles for animals for the following reasons. (i) The Vectored vaccines are of the safe subunit type and express multiple antigens. (ii) Both humoral and cellular immune responses against pathogens can be induced in animals. (iii) They have a potential for long-term induction of protective immunity against pathogens in animals. 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 family, causes considerable economic losses in the poultry industry by inducing bursal destruction, immunosuppression, and high mortality in young chickens (21, 23, 42). Although live IBDV vaccines are highly efficacious (18), the vaccine efficacy decreases in the presence of maternal antibodies (23, 38, 42), and some of them cause bursal atrophy (25). Highly efficacious and safe IBD vaccines are needed. The VP2 protein is the conformational protective antigen: VP2 or the neutralizing antibodies can elicit complete protection against a lethal IBDV challenge (2, 4, 9, 10, 14, 23). We previously developed a recombinant MDV (rMDV) expressing VP2 antigen under control of the simian virus 40 (SV40) early promoter and showed that it was safe for chickens. However, the efficacy was partial and did not persist for a long time (39, 40). Recombinant HVT (rHVT) expressing the VP2 antigen under the control of a cytomegalovirus (CMV) promoter also induced partial protection in chickens when one dose was used (8). Further studies are required to improve the vaccine efficacy of MDV-Vectored vaccines. In order to determine the association between the amounts of antigen expressed in an HVT Herpesvirus Vector and the vaccine efficacy, we developed two rHVTs expressing different amounts of IBDV VP2 antigens under the control of CMV or Pec promoters. The Pec promoter is a new promoter consisting of a CMV enhancer and a β-actin promoter and has promoter activity in chicken embryo fibroblasts (CEFs) approximately three times stronger than that of the CMV promoter (M. Kubomura, A. Fujisawa, T. Okuda, S. Saitoh, and A. Yasuda, unpublished data). The present study indicated that the amount of antigen expressed in the HVT Herpesvirus Vector was correlated with the vaccine efficacy against IBD. The rHVT expressing larger amounts of VP2 antigen conferred complete protection against the lethal IBDV challenge, which was expected to persist for the lifetime of the chickens.

  • complete long lasting protection against lethal infectious bursal disease virus challenge by a single vaccination with an avian Herpesvirus Vector expressing vp2 antigens
    Journal of Virology, 2002
    Co-Authors: Kenji Tsukamoto, S Saito, S Saeki, T Sato, Nobuhiko Tanimura, T Isobe, Masaji Mase, Tadao Imada, N Yuasa, Shigeo Yamaguchi
    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/beta-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.

S Saeki - One of the best experts on this subject based on the ideXlab platform.

  • complete long lasting protection against lethal infectious bursal disease virus challenge by a single vaccination with an avian Herpesvirus Vector expressing vp2 antigens
    Journal of Virology, 2002
    Co-Authors: Kenji Tsukamoto, S Saito, S Saeki, T Sato, Nobuhiko Tanimura, T Isobe, Masaji Mase, Tadao Imada, N Yuasa, Shigeo Yamaguchi
    Abstract:

    Replication-competent Herpesvirus Vectors are prospective vaccine vehicles for animals for the following reasons. (i) The Vectored vaccines are of the safe subunit type and express multiple antigens. (ii) Both humoral and cellular immune responses against pathogens can be induced in animals. (iii) They have a potential for long-term induction of protective immunity against pathogens in animals. 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 family, causes considerable economic losses in the poultry industry by inducing bursal destruction, immunosuppression, and high mortality in young chickens (21, 23, 42). Although live IBDV vaccines are highly efficacious (18), the vaccine efficacy decreases in the presence of maternal antibodies (23, 38, 42), and some of them cause bursal atrophy (25). Highly efficacious and safe IBD vaccines are needed. The VP2 protein is the conformational protective antigen: VP2 or the neutralizing antibodies can elicit complete protection against a lethal IBDV challenge (2, 4, 9, 10, 14, 23). We previously developed a recombinant MDV (rMDV) expressing VP2 antigen under control of the simian virus 40 (SV40) early promoter and showed that it was safe for chickens. However, the efficacy was partial and did not persist for a long time (39, 40). Recombinant HVT (rHVT) expressing the VP2 antigen under the control of a cytomegalovirus (CMV) promoter also induced partial protection in chickens when one dose was used (8). Further studies are required to improve the vaccine efficacy of MDV-Vectored vaccines. In order to determine the association between the amounts of antigen expressed in an HVT Herpesvirus Vector and the vaccine efficacy, we developed two rHVTs expressing different amounts of IBDV VP2 antigens under the control of CMV or Pec promoters. The Pec promoter is a new promoter consisting of a CMV enhancer and a β-actin promoter and has promoter activity in chicken embryo fibroblasts (CEFs) approximately three times stronger than that of the CMV promoter (M. Kubomura, A. Fujisawa, T. Okuda, S. Saitoh, and A. Yasuda, unpublished data). The present study indicated that the amount of antigen expressed in the HVT Herpesvirus Vector was correlated with the vaccine efficacy against IBD. The rHVT expressing larger amounts of VP2 antigen conferred complete protection against the lethal IBDV challenge, which was expected to persist for the lifetime of the chickens.

  • complete long lasting protection against lethal infectious bursal disease virus challenge by a single vaccination with an avian Herpesvirus Vector expressing vp2 antigens
    Journal of Virology, 2002
    Co-Authors: Kenji Tsukamoto, S Saito, S Saeki, T Sato, Nobuhiko Tanimura, T Isobe, Masaji Mase, Tadao Imada, N Yuasa, Shigeo Yamaguchi
    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/beta-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.