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Sultankulova K.T.,Research Institute for Biological Safety Problems RIBSP | Chervyakova O.V.,Research Institute for Biological Safety Problems RIBSP | Kozhabergenov N.S.,Research Institute for Biological Safety Problems RIBSP | Shorayeva K.A.,Research Institute for Biological Safety Problems RIBSP | And 5 more authors.
Scientific World Journal | Year: 2014

The paper describes comparative evaluation of IAVchip DNA microarray, reverse transcription PCR (RT-PCR), and real-time RT-PCR versus virus isolation in chicken embryos and shows their diagnostic effectiveness in detection and subtyping of influenza A virus. The tests were evaluated with use of 185 specimens from humans, animals, and birds. IAVchip DNA microarray demonstrates higher diagnostic effectiveness (99.45%) in early influenza A diagnosis as compared to the real-time PCR (98.38%) and RT-PCR (96.22%), thus showing its clear superiority. Diagnostic sensitivity of IAVchip DNA microarray (100%) exceeds the same of RT-PCR (95.95%) and real-time RT-PCR (97.96%) in the range of estimated confidence intervals. IAVchip DNA microarray and real-time RT-PCR displayed equal diagnostic specificity (98.85%), while diagnostic specificity of RT-PCR was 96.40%. IAVchip DNA microarray has an advantage over the other tests for influenza A diagnosis and virus identification as a more rapid method that allows performing simultaneous detection and subtyping of about tens of specimens within one experiment during 8-10 hours. The developed IAVchip DNA microarray is a general test tool that enables identifying simultaneously 16 hemagglutinin (HA) and 9 neuraminidase (NA) subtypes of influenza A virus and also to screen the influenza A viruses from humans, animals, and birds by M and NP genes. © 2014 K. T. Sultankulova et al.


Tabynov K.,Research Institute for Biological Safety Problems RIBSP | Khairullin B.,Research Institute for Biological Safety Problems RIBSP | Kydyrbayev Z.,Research Institute for Biological Safety Problems RIBSP | Sandybayev N.,Research Institute for Biological Safety Problems RIBSP | And 6 more authors.
Journal of Vaccines and Vaccination | Year: 2013

We performed a randomized, blinded, dose-dependent placebo-controlled phase I clinical study of single administration of Refluvac®, a monovalent inactivated whole-virion vaccine against pandemic influenza A(H1N1) pdm09 containing aluminum adjuvant, in healthy volunteers aged 18-60. Single intramuscular injection at doses of 3.75, 7.5, or 15.0 μg hemagglutinin (HA) identified no safety issues in adult volunteers (n=12 per group); no severe or serious vaccination-related adverse events were observed. Only mild/moderate local adverse events (n= 3/12, 25% in 7.5 μg HA arm,) and one moderate systemic reaction (n=1/12, 8.3% in 15.0 μg HA arm) were observed. In volunteers vaccinated at 3.75 μg HA, the proportion of subjects with 4-fold seroconversion was 75%, the level of seroprotection was also 75%, the antibody titer increase was 10.7-fold, and the geometric mean titer (GMT) of antibodies to A/H1N1pdm09 was 53.4; for the 7.5 μg HA dose, the proportion of 4-fold seroconversion was 75%, the antibody titer increase was 32.0-fold, the GMT was 160.0, and the level of seroprotection was 75%. When administered at a higher dose (15 μg HA), the proportion of subjects with protective antibody titers increased from 75% to 83%; however, the GMT and antibody titer increase were not significantly different (P>0.05) to the group vaccinated at 7.5 μg HA. Phase II clinical studies of the 3.75 and 7.5 μg HA doses of Refluvac® vaccine should be performed in a larger cohort of healthy volunteers aged 18-60. The effective immunogenicity of low doses of Refluvac® vaccine may enable increased production of pandemic influenza vaccines, and thus provide more people with a safe, effective vaccine. © 2013 Tabynov K, et al.


Tabynov K.,Research Institute for Biological Safety Problems RIBSP | Kydyrbayev Z.,Research Institute for Biological Safety Problems RIBSP | Ryskeldinova S.,Research Institute for Biological Safety Problems RIBSP | Assanzhanova N.,Research Institute for Biological Safety Problems RIBSP | Sansyzbay A.,Research Institute for Biological Safety Problems RIBSP
Vaccine | Year: 2014

We previously created a live vaccine against equine influenza based the new reassortant cold-adapted (Ca) strain A/HK/Otar/6:2/2010. The live vaccine contains surface proteins (HA, NA) from the wild-type virus A/equine/Otar/764/2007 (n{cyrillic}3N8; American Lineage Florida Clade 2), and internal proteins (PB2, PB1, PA, NP, M, NS) from the attenuated Ca donor virus A/Hong Kong/1/68/162/35CA (H3N2). To determine the safety and duration of the protective immune responses, 90 yearlings were intranasally vaccinated in single mode, double mode at an interval of 42 days (107.0 EID50/animal for both vaccinations), or with PBS (control group). Ten animals from each group were challenged with the homologous wild-type virus A/equine/Otar/764/07 (n{cyrillic}3N8) at 1, 2, 3, 4, 5, 6, 9 and 12 months after vaccination. Similarly, 10 animals from each group were challenged with the heterologous wild-type virus A/equine/Sydney/2888-8/07 (n{cyrillic}3N8; American Lineage Florida Clade 1) 12 months after vaccination. The vaccine was completely safe, and single intranasal vaccination of yearlings was capable of inducing statistically significant (from P=0.03 to P<0.0001) clinical and virological protection against the homologous virus; however, only double mode vaccination generated significant (from P=0.02 to P<0.0001) protection against the heterologous virus at 12 months (observation period). Interestingly, this vaccine enables the differentiation of infected and vaccinated animals. On this basis of this study, we recommend double intranasal administration of this vaccine at an interval of 42 days in veterinary practice. © 2014 The Authors.


Tabynov K.,Research Institute for Biological Safety Problems RIBSP | Kydyrbayev Z.,Research Institute for Biological Safety Problems RIBSP | Sansyzbay A.,Research Institute for Biological Safety Problems RIBSP | Khairullin B.,Research Institute for Biological Safety Problems RIBSP | And 4 more authors.
Virologica Sinica | Year: 2012

This paper presents the results of a pre-clinical study of the immunogenicity and efficacy of an egg-derived, inactivated, whole-virion adjuvanted vaccine (Refluvac®) on ferret models. For this purpose, groups of eight ferrets (6 to 7 months old) were injected with 0.5 mL of vaccine specimens containing 3.75, 7.5 or 15.0 μg of virus hemagglutinin. Administration was intramuscular and given either as a single dose or as two doses 14 days apart. All vaccine specimens manifested immunogenicity in ferrets for single (HI titer, from 51 ± 7 to 160 ± 23) and double (HI titer, from 697 ± 120 to 829 ± 117) administrations. To assess the protective effects of the vaccine, ferrets from the vaccinated and control groups were infected intranasally with pandemic virus A/California/7/09 (H1N1) pdm09 at a dose of 106 EID50/0.5 mL. Fourteen days post-infection, the ferrets inoculated with single or double vaccines containing 3.75, 7.5 or 15.0 μg of hemagglutinin per dose showed no signs of influenza infection, weight loss, or body temperature rise, and no premature deaths occurred. The number of vaccinated ferrets shedding the virus via the upper airway, as well as the amount of virus shed after infection, was significantly reduced in comparison with animals from the control group. Based on our results, we suggest that a single vaccination at a dose of 3.75 or 7.5 μg hemagglutinin be used for Phase I clinical trials. © 2012 Wuhan Institute of Virology, CAS and Springer-Verlag Berlin Heidelberg.


Kondybaeva Z.,Research Institute for Biological Safety Problems RIBSP | Yershebulov Z.,Research Institute for Biological Safety Problems RIBSP | Sultankulova K.,Research Institute for Biological Safety Problems RIBSP | Nakhanov A.,Research Institute for Biological Safety Problems RIBSP | And 8 more authors.
Life Science Journal | Year: 2014

This paper presents the results of the development of the optimal conditions for new TB-FLU Esat6 2A Ag85A recombinant strain cultivation in Vero cell culture. The studies revealed that the maximum accumulation of the virus in cell culture can be achieved with 0,001 TCD50/cell infecting dose, 34,0 ± 0,5 °C incubation temperature and 72 hours of incubation time. The highest reproductive activity of the virus was obtained using trypsin (Sigma # T4049, Lot10D169, # Lot020M7022T1426-1g) at a concentration 2 μg/ml. The TB-FLU Esat6 2A Ag85A recombinant strain expressing mycobacterial proteins Esat6 and Ag85A with open reading frame of NS1 protein of the influenza virus is genetically stable and capable to maintain enthetic inserts during 10 consecutive passages in Vero cell culture. Subject to the established cultivation parameters the recombinant virus accumulation level reached up to 7,75 ± 0,08 lg TCD50/cm3 with 7,0 log2hemagglutinating titer, which is quite suitable for the development of a TB vaccine for human health care.


Koshemetov Z.,Research Institute for Biological Safety Problems RIBSP | Sansyzbay A.,Research Institute for Biological Safety Problems RIBSP | Sandybayev N.,Research Institute for Biological Safety Problems RIBSP | Abduraimov Y.,Research Institute for Biological Safety Problems RIBSP | And 6 more authors.
Life Science Journal | Year: 2014

The monitoring researches and laboratory confirmation of peste des petits ruminants on the territory of the Central Asia is carried out. As a result of the conducted laboratory researches of the delivered biomaterials from sick, died goats and sheep from various regions of the Republic of Kazakhstan, Tajikistan and Kyrgyzstan it has been demonstrated that virus of this disease is present. The map of spread of peste des petits ruminants on the territory of the Central Asia is made.


Koshemetov Z.,Research Institute for Biological Safety Problems RIBSP | Sandybayev N.,Research Institute for Biological Safety Problems RIBSP | Sansyzbay A.,Research Institute for Biological Safety Problems RIBSP | Orynbayev M.,Research Institute for Biological Safety Problems RIBSP | And 8 more authors.
Life Science Journal | Year: 2014

The article contains the biological characterization of pasteurellosis strains isolated from dead saiga antelopes in Kazakhstan. Results demonstrated that pasteurellosis strains isolated from saiga antelopes from different periods had identical biological characteristics.


Tlenchieva T.M.,Research Institute for Biological Safety Problems RIBSP | Sultankulova K.T.,Research Institute for Biological Safety Problems RIBSP | Shoraeva K.A.,Research Institute for Biological Safety Problems RIBSP | Strochkov V.M.,Research Institute for Biological Safety Problems RIBSP | And 5 more authors.
Research Journal of Pharmaceutical, Biological and Chemical Sciences | Year: 2015

The clostridial bacteria emerged from dead saiga in 2010-2013 were identified on the basis of 16S rRNA gene as perfringens species and by the presence of plc gene, encoding only alpha-toxin and were classified as type A. The genetic variation of Clostridium perfringens alpha-toxin strains emerged from saiga was characterized in 2010-2013. N- and C- domains of Clostridium perfringens alpha-toxin strain structure, emerged from the saiga in 2010-2012 showed a very high conservatism. The structure of Clostridium perfringens alpha-toxin strain, 2013 revealed previously unknown mutations - 4 amino acid substitutions: Ala13Thr (threonine → alanine), Val47Ile (valine, isoleucine →), Ala202Asp (alanine → aspartic acid), Thr205Ala (threonine → Alanine) in the N-domain of alpha-toxin and 1 replacement of Ser363Pro (serine → proline) in the C-domain. We may assume that this mutation affects the reduction of alpha-toxin toxicity and as a result, causes Clostridium perfringens pathogenicity reduction. The degree of identity in the N-terminal catalytic domain of alpha-toxin reaches 98.4% and in C domain responsible for the binding to membranes the identity makes 99.2%. Plc gene sequence of the strains Clostridium/Saigas/2010/ZKO/KZ, Clostridium/Saigas/2011/ZKO/KZ, Clostridium/Saigas/2012/Kostanay/KZ and Clostridium/Saigas/2013/Kostanay/KZ are deposited in the GenBankdatbase under the numbers KP143658, KP143659, KP143660, KP143661, respectively.


PubMed | Ohio State University, Research Institute for Biological Safety Problems RIBSP and Agrarian National University
Type: | Journal: Veterinary microbiology | Year: 2016

The efficacy of a novel BEI-inactivated porcine reproductive and respiratory syndrome virus (PRRSV) candidate vaccine in pigs, developed at RIBSP Republic of Kazakhstan and delivered with an adjuvant Montanide Gel 01 ST (D/KV/ADJ) was compared with a commercial killed PRRSV vaccine (NVDC-JXA1, C/KV/ADJ) used widely in swine herds of the Republic of Kazakhstan. Clinical parameters (body temperature and respiratory disease scores), virological and immunological profiles [ELISA and virus neutralizing (VN) antibody titers], macroscopic lung lesions and viral load in the lungs (quantitative real-time PCR and cell culture assay) were assessed in vaccinated and both genotype 1 and 2 PRRSV challenged pigs. Our results showed that the commercial vaccine failed to protect pigs adequately against the clinical disease, viremia and lung lesions caused by the challenged field isolates, Kazakh strains of PRRSV type 1 and type 2 genotypes. In contrast, clinical protection, absence of viremia and lung lesions in D/KV/ADJ vaccinated pigs was associated with generation of VN antibodies in both homologous vaccine strain LKZ/2010 (PRRSV type 2) and a heterogeneous type 1 PRRSV strain (CM/08) challenged pigs. Thus, our data indicated the induction of cross-protective VN antibodies by D/KV/ADJ vaccine, and importantly demonstrated that an inactivated PRRSV vaccine could also induce cross-protective response across the viral genotype.

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