The Experts below are selected from a list of 55149 Experts worldwide ranked by ideXlab platform
Haifeng Chen - One of the best experts on this subject based on the ideXlab platform.
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adeno associated Viral Vector serotype 9 based gene therapy for niemann pick disease type a
Science Translational Medicine, 2019Co-Authors: Lluis Samaranch, Azucena Perezcanamas, Beatriz Sotohuelin, Vivek Sudhakar, Jeronimo Juradoarjona, Piotr Hadaczek, Jesus Avila, John Bringas, Josefina Casas, Haifeng ChenAbstract:Niemann-Pick disease type A (NPD-A) is a lysosomal storage disorder characterized by neurodegeneration and early death. It is caused by loss-of-function mutations in the gene encoding for acid sphingomyelinase (ASM), which hydrolyzes sphingomyelin into ceramide. Here, we evaluated the safety of cerebellomedullary (CM) cistern injection of adeno-associated Viral Vector serotype 9 encoding human ASM (AAV9-hASM) in nonhuman primates (NHP). We also evaluated its therapeutic benefit in a mouse model of the disease (ASM-KO mice). We found that CM injection in NHP resulted in widespread transgene expression within brain and spinal cord cells without signs of toxicity. CM injection in the ASM-KO mouse model resulted in hASM expression in cerebrospinal fluid and in different brain areas without triggering an inflammatory response. In contrast, direct cerebellar injection of AAV9-hASM triggered immune response. We also identified a minimally effective therapeutic dose for CM injection of AAV9-hASM in mice. Two months after administration, the treatment prevented motor and memory impairment, sphingomyelin (SM) accumulation, lysosomal enlargement, and neuronal death in ASM-KO mice. ASM activity was also detected in plasma from AAV9-hASM CM-injected ASM-KO mice, along with reduced SM amount and decreased inflammation in the liver. Our results support CM injection for future AAV9-based clinical trials in NPD-A as well as other lysosomal storage brain disorders.
Kaissar Tabynov - One of the best experts on this subject based on the ideXlab platform.
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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, 2017Co-Authors: Aigerim Mailybayeva, Sholpan Ryskeldinova, Abylai Sansyzbay, Nadezhda Zinina, Bolat Yespembetov, Gourapura J Renukaradhya, Nikolai Petrovsky, Kaissar TabynovAbstract: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.
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an influenza Viral Vector brucella abortus vaccine induces good cross protection against brucella melitensis infection in pregnant heifers
Vaccine, 2015Co-Authors: Kaissar Tabynov, Sholpan Ryskeldinova, Abylai SansyzbayAbstract:Abstract Brucella melitensis can be transmitted and cause disease in cattle herds as a result of inadequate management of mixed livestock farms. Ideally, vaccines against Brucella abortus for cattle should also provide cross-protection against B. melitensis . Previously we created a novel influenza Viral Vector B. abortus (Flu-BA) vaccine expressing the Brucella ribosomal proteins L7/L12 or Omp16. This study demonstrated Flu-BA vaccine with adjuvant Montanide Gel01 provided 100% protection against abortion in vaccinated pregnant heifers and good cross-protection of the heifers and their calves or fetuses (90–100%) after challenge with B. melitensis 16 M; the level of protection provided by Flu-BA was comparable to the commercial vaccine B. abortus S19. In terms of the index of infection and colonization of Brucella in tissues, both vaccines demonstrated significant ( P = 0.02 to P B. melitensis 16 M infection compared to the negative control group (PBS + Montanide Gel01). Thus, we conclude the Flu-BA vaccine provides cross-protection against B. melitensis infection in pregnant heifers.
Arifa S Khan - One of the best experts on this subject based on the ideXlab platform.
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the brighton collaboration Viral Vector vaccines safety working group v3swg
Vaccine, 2015Co-Authors: Robert T Chen, Marc Gurwith, Richard C Condit, Jeanlouis Excler, Baevin Carbery, Lisa Mac, Kenneth I Berns, Louisa E Chapman, Michael Hendry, Arifa S KhanAbstract:Recombinant Viral Vectors provide an effective means for heterologous antigen expression in vivo and thus represent promising platforms for developing novel vaccines against human pathogens from Ebola to tuberculosis. An increasing number of candidate Viral Vector vaccines are entering human clinical trials. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to improve our ability to anticipate potential safety issues and meaningfully assess or interpret safety data, thereby facilitating greater public acceptance when licensed.
Marc Gurwith - One of the best experts on this subject based on the ideXlab platform.
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brighton collaboration Viral Vector vaccines safety working group v3swg standardized template for collection of key information for benefit risk assessment of live attenuated Viral vaccines
Vaccine, 2020Co-Authors: Marc Gurwith, Richard C Condit, Jeanlouis Excler, James S Robertson, Denny Kim, Patricia E Fast, Stephen Drew, David Wood, Bettina Klug, Mike WhelanAbstract:Several live-attenuated Viral vaccine candidates are among the COVID-19 vaccines in development. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of live-attenuated Viral vaccines. This will help key stakeholders assess potential safety issues and understand the benefit-risk of such vaccines. The standardized and structured assessment provided by the template would also help to contribute to improved communication and support public acceptance of licensed live-attenuated Viral vaccines.
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the brighton collaboration Viral Vector vaccines safety working group v3swg
Vaccine, 2015Co-Authors: Robert T Chen, Marc Gurwith, Richard C Condit, Jeanlouis Excler, Baevin Carbery, Lisa Mac, Kenneth I Berns, Louisa E Chapman, Michael Hendry, Arifa S KhanAbstract:Recombinant Viral Vectors provide an effective means for heterologous antigen expression in vivo and thus represent promising platforms for developing novel vaccines against human pathogens from Ebola to tuberculosis. An increasing number of candidate Viral Vector vaccines are entering human clinical trials. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to improve our ability to anticipate potential safety issues and meaningfully assess or interpret safety data, thereby facilitating greater public acceptance when licensed.
Sholpan Ryskeldinova - One of the best experts on this subject based on the ideXlab platform.
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Registered Influenza Viral Vector Based Brucella abortus Vaccine for Cattle in Kazakhstan: Age-Wise Safety and Efficacy Studies
'Frontiers Media SA', 2021Co-Authors: Sholpan Ryskeldinova, Nadezhda Zinina, Zhailaubay Kydyrbayev, Bolat Yespembetov, Yerken Kozhamkulov, Dulat Inkarbekov, Nurika Assanzhanova, Aigerim Mailybayeva, Dina BugybayevaAbstract:A novel influenza Viral Vector based Brucella abortus vaccine (Flu-BA) was introduced for use in cattle in Kazakhstan in 2019. In this study, the safety and efficacy of the vaccine was evaluated in male and female cattle at different ages, and during pregnancy as a part of its registration process. Our data demonstrated that the Flu-BA vaccine was safe after prime or booster vaccination in calves (5–7 months old male and female), heifers (15–17 months old) and cows (6–7 years old) and was not abortogenic in pregnant animals. A mild, localized granuloma was observed at the Flu-BA injection site. Vaccinated animals did not show signs of influenza infection or reduced milk production in dairy cows, and the influenza Viral Vector (IVV) was not recovered from nasal swabs or milk. Vaccinated animals in all age groups demonstrated increased IgG antibody responses against Brucella Omp16 and L7/L12 proteins with calves demonstrating the greatest increase in humoral responses. Following experimental challenge with B. abortus 544, vaccinates demonstrated greater protection and no signs of clinical disease, including abortion, were observed. The vaccine effectiveness against B. abortus 544 infection was 75, 60 and 60%, respectively, in calves, heifers and adult cows. Brucella were not isolated from calves of vaccinated cattle that were experimentally challenged during pregnancy. Our data suggests that the Flu-BA vaccine is safe and efficacious in cattle, including pregnant animals; and can therefore be administered to cattle of any age
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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, 2017Co-Authors: Aigerim Mailybayeva, Sholpan Ryskeldinova, Abylai Sansyzbay, Nadezhda Zinina, Bolat Yespembetov, Gourapura J Renukaradhya, Nikolai Petrovsky, Kaissar TabynovAbstract: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.
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an influenza Viral Vector brucella abortus vaccine induces good cross protection against brucella melitensis infection in pregnant heifers
Vaccine, 2015Co-Authors: Kaissar Tabynov, Sholpan Ryskeldinova, Abylai SansyzbayAbstract:Abstract Brucella melitensis can be transmitted and cause disease in cattle herds as a result of inadequate management of mixed livestock farms. Ideally, vaccines against Brucella abortus for cattle should also provide cross-protection against B. melitensis . Previously we created a novel influenza Viral Vector B. abortus (Flu-BA) vaccine expressing the Brucella ribosomal proteins L7/L12 or Omp16. This study demonstrated Flu-BA vaccine with adjuvant Montanide Gel01 provided 100% protection against abortion in vaccinated pregnant heifers and good cross-protection of the heifers and their calves or fetuses (90–100%) after challenge with B. melitensis 16 M; the level of protection provided by Flu-BA was comparable to the commercial vaccine B. abortus S19. In terms of the index of infection and colonization of Brucella in tissues, both vaccines demonstrated significant ( P = 0.02 to P B. melitensis 16 M infection compared to the negative control group (PBS + Montanide Gel01). Thus, we conclude the Flu-BA vaccine provides cross-protection against B. melitensis infection in pregnant heifers.
