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Improved influenza viral vector based Brucella abortus vaccine induces robust B and T-cell responses and protection against Brucella melitensis infection in pregnant sheep and goats.
PLoS One 2017; 12(10):e0186484Plos

Abstract

We previously developed a potent candidate vaccine against bovine brucellosis caused by Brucella abortus using the influenza viral vector expressing Brucella Omp16 and L7/L12 proteins (Flu-BA). Our success in the Flu-BA vaccine trial in cattle and results of a pilot study in non-pregnant small ruminants prompted us in the current study to test its efficacy against B. melitensis infection in pregnant sheep and goats. In this study, we improved the Flu-BA vaccine formulation and immunization method to achieve maximum efficacy and safety. The Flu-BA vaccine formulation had two additional proteins Omp19 and SOD, and administered thrice with 20% Montanide Gel01 adjuvant, simultaneously by both subcutaneous and conjunctival routes at 21 days intervals in pregnant sheep and goats. At 42 days post-vaccination (DPV) we detected antigen-specific IgG antibodies predominantly of IgG2a isotype but also IgG1, and also detected a strong lymphocyte recall response with IFN-γ production. Importantly, our candidate vaccine prevented abortion in 66.7% and 77.8% of pregnant sheep and goats, respectively. Furthermore, complete protection (absence of live B. melitensis 16M) was observed in 55.6% and 66.7% of challenged sheep and goats, and 72.7% and 90.0% of their fetuses (lambs/yeanlings), respectively. The severity of B. melitensis 16M infection in vaccinated sheep and goats and their fetuses (index of infection and rates of Brucella colonization in tissues) was significantly lower than in control groups. None of the protection parameters after vaccination with Flu-BA vaccine were statistically inferior to protection seen with the commercial B. melitensis Rev.1 vaccine (protection against abortion and vaccination efficacy, alpha = 0.18-0.34, infection index, P = 0.37-0.77, Brucella colonization, P = 0.16 to P > 0.99). In conclusion, our improved Flu-BA vaccine formulation and delivery method were found safe and effective in protecting pregnant sheep and goats against adverse consequences of B. melitensis infection.

Authors+Show Affiliations

Laboratory of Infectious Disease Prevention, Research Institute for Biological Safety Problems, Zhambulskaya Oblast, Kordaiskiy Rayon, Gvardeiskiy, Republic of Kazakhstan.Laboratory of Microbiology, Research Institute for Biological Safety Problems, Zhambulskaya Oblast, Kordaiskiy Rayon, Gvardeiskiy, Republic of Kazakhstan.Laboratory of Infectious Disease Prevention, Research Institute for Biological Safety Problems, Zhambulskaya Oblast, Kordaiskiy Rayon, Gvardeiskiy, Republic of Kazakhstan.Laboratory of Microbiology, Research Institute for Biological Safety Problems, Zhambulskaya Oblast, Kordaiskiy Rayon, Gvardeiskiy, Republic of Kazakhstan.Laboratory of Infectious Disease Prevention, Research Institute for Biological Safety Problems, Zhambulskaya Oblast, Kordaiskiy Rayon, Gvardeiskiy, Republic of Kazakhstan.Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University (OSU), Wooster, United States of America.Vaxine Pty Ltd and Flinders University, Bedford Park, Australia.Laboratory of Infectious Disease Prevention, Research Institute for Biological Safety Problems, Zhambulskaya Oblast, Kordaiskiy Rayon, Gvardeiskiy, Republic of Kazakhstan. Vaxine Pty Ltd and Flinders University, Bedford Park, Australia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29023541

Citation

Mailybayeva, Aigerim, et al. "Improved Influenza Viral Vector Based Brucella Abortus Vaccine Induces Robust B and T-cell Responses and Protection Against Brucella Melitensis Infection in Pregnant Sheep and Goats." PloS One, vol. 12, no. 10, 2017, pp. e0186484.
Mailybayeva A, Yespembetov B, Ryskeldinova S, et al. Improved influenza viral vector based Brucella abortus vaccine induces robust B and T-cell responses and protection against Brucella melitensis infection in pregnant sheep and goats. PLoS ONE. 2017;12(10):e0186484.
Mailybayeva, A., Yespembetov, B., Ryskeldinova, S., Zinina, N., Sansyzbay, A., Renukaradhya, G. J., ... Tabynov, K. (2017). Improved influenza viral vector based Brucella abortus vaccine induces robust B and T-cell responses and protection against Brucella melitensis infection in pregnant sheep and goats. PloS One, 12(10), pp. e0186484. doi:10.1371/journal.pone.0186484.
Mailybayeva A, et al. Improved Influenza Viral Vector Based Brucella Abortus Vaccine Induces Robust B and T-cell Responses and Protection Against Brucella Melitensis Infection in Pregnant Sheep and Goats. PLoS ONE. 2017;12(10):e0186484. PubMed PMID: 29023541.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Improved influenza viral vector based Brucella abortus vaccine induces robust B and T-cell responses and protection against Brucella melitensis infection in pregnant sheep and goats. AU - Mailybayeva,Aigerim, AU - Yespembetov,Bolat, AU - Ryskeldinova,Sholpan, AU - Zinina,Nadezhda, AU - Sansyzbay,Abylai, AU - Renukaradhya,Gourapura J, AU - Petrovsky,Nikolai, AU - Tabynov,Kaissar, Y1 - 2017/10/12/ PY - 2017/08/27/received PY - 2017/10/02/accepted PY - 2017/10/13/entrez PY - 2017/10/13/pubmed PY - 2017/10/25/medline SP - e0186484 EP - e0186484 JF - PloS one JO - PLoS ONE VL - 12 IS - 10 N2 - We previously developed a potent candidate vaccine against bovine brucellosis caused by Brucella abortus using the influenza viral vector expressing Brucella Omp16 and L7/L12 proteins (Flu-BA). Our success in the Flu-BA vaccine trial in cattle and results of a pilot study in non-pregnant small ruminants prompted us in the current study to test its efficacy against B. melitensis infection in pregnant sheep and goats. In this study, we improved the Flu-BA vaccine formulation and immunization method to achieve maximum efficacy and safety. The Flu-BA vaccine formulation had two additional proteins Omp19 and SOD, and administered thrice with 20% Montanide Gel01 adjuvant, simultaneously by both subcutaneous and conjunctival routes at 21 days intervals in pregnant sheep and goats. At 42 days post-vaccination (DPV) we detected antigen-specific IgG antibodies predominantly of IgG2a isotype but also IgG1, and also detected a strong lymphocyte recall response with IFN-γ production. Importantly, our candidate vaccine prevented abortion in 66.7% and 77.8% of pregnant sheep and goats, respectively. Furthermore, complete protection (absence of live B. melitensis 16M) was observed in 55.6% and 66.7% of challenged sheep and goats, and 72.7% and 90.0% of their fetuses (lambs/yeanlings), respectively. The severity of B. melitensis 16M infection in vaccinated sheep and goats and their fetuses (index of infection and rates of Brucella colonization in tissues) was significantly lower than in control groups. None of the protection parameters after vaccination with Flu-BA vaccine were statistically inferior to protection seen with the commercial B. melitensis Rev.1 vaccine (protection against abortion and vaccination efficacy, alpha = 0.18-0.34, infection index, P = 0.37-0.77, Brucella colonization, P = 0.16 to P > 0.99). In conclusion, our improved Flu-BA vaccine formulation and delivery method were found safe and effective in protecting pregnant sheep and goats against adverse consequences of B. melitensis infection. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/29023541/Improved_influenza_viral_vector_based_Brucella_abortus_vaccine_induces_robust_B_and_T_cell_responses_and_protection_against_Brucella_melitensis_infection_in_pregnant_sheep_and_goats_ L2 - http://dx.plos.org/10.1371/journal.pone.0186484 DB - PRIME DP - Unbound Medicine ER -