Papers by Dina Bugybayeva
Research Square (Research Square), Aug 11, 2020
Background: A new candidate vector vaccine against human brucellosis based on recombinant in uenz... more Background: A new candidate vector vaccine against human brucellosis based on recombinant in uenza viral vectors (rIVV) subtypes H5N1 expressing Brucella Omp16, L7/L12, Omp19 or Cu-Zn SOD proteins has been developed. This paper presents the results of the study of the safety and protective properties of the vaccine with various options of administering, dosing and frequency of use on guinea pigs. Methods: The safety of the vaccine was assessed based on the general condition, behavior and dynamics of a guinea pig weight-gain test. The effectiveness of the new anti-brucellosis vector vaccine was determined by studying its protective effect after conjunctival, intranasal and sublingual administration in doses 10 5 EID 50 , 10 6 EID 50 and 10 7 EID 50 during prime and boost vaccinations of animals, followed by challenge with a virulent strain of B. mellitensis 16M infection. For sake of comparison, the commercial B. melitensis Rev.1 vaccine was used as a control. The protective properties of vaccines were assessed by quantitation of Brucella colonization in organs and tissues of infected animals and compared to the control groups. Results: It was found that the vaccine after prime and booster immunization using conjunctival, intranasal and sublingual routes of administration, as well as after using various doses of vaccine were safe for guinea pigs. The most optimal way of using the vaccine has been established: double intranasal immunization of guinea pigs at a dose of 10 6 EID 50 , which provides 80% protection of guinea pigs from B. melitensis 16M infection (P < 0.05), which is comparable to the results of the effectiveness of the commercial B. melitensis Rev.1 vaccine. Conclusions: We developed effective vaccine candidate against brucellosis and developed its immunization protocol in guinea pig model. We believe that this study is a substantial step for using the vaccine for future pre-clinical and clinical trials in human.
Infectious Diseases of Poverty, Feb 16, 2021
Background: A new candidate vector vaccine against human brucellosis based on recombinant influen... more Background: A new candidate vector vaccine against human brucellosis based on recombinant influenza viral vectors (rIVV) subtypes H5N1 expressing Brucella outer membrane protein (Omp) 16, L7/L12, Omp19 or Cu-Zn SOD proteins has been developed. This paper presents the results of the study of protection of the vaccine using on guinea pigs, including various options of administering, dose and frequency. Provided data of the novel vaccine candidate will contribute to its further movement into the preclinical stage study. Methods: General states of guinea pigs was assessed based on behavior and dynamics of a guinea pig weight-gain test. The effectiveness of the new anti-brucellosis vector vaccine was determined by studying its protective effect after conjunctival, intranasal and sublingual administration in doses 10 5 EID 50 , 10 6 EID 50 and 10 7 EID 50 during prime and boost vaccinations of animals, followed by challenge with a virulent strain of B. melitensis 16 M infection. For sake of comparison, the commercial B. melitensis Rev.1 vaccine was used as a control. The protective properties of vaccines were assessed by quantitation of Brucella colonization in organs and tissues of infected animals and compared to the control groups. Results: It was observed a gradual increase in body weight of guinea pigs after prime and booster immunization with the vaccine using conjunctival, intranasal and sublingual routes of administration, as well as after using various doses of vaccine. The most optimal way of using the vaccine has been established: double intranasal immunization of guinea pigs at a dose of 10 6 EID 50 , which provides 80% protection of guinea pigs from B. melitensis 16 M infection (P < 0.05), which is comparable to the results of the effectiveness of the commercial B. melitensis Rev.1 vaccine. Conclusions: We developed effective human vaccine candidate against brucellosis and developed its immunization protocol in guinea pig model. We believe that because of these studies, the proposed vaccine has achieved the best level of protection, which in turn provides a basis for its further promotion.
Vaccines
Swine influenza A viruses (SwIAVs) are pathogens of both veterinary and medical significance. Int... more Swine influenza A viruses (SwIAVs) are pathogens of both veterinary and medical significance. Intranasal (IN) vaccination has the potential to reduce flu infection. We investigated the efficacy of split SwIAV H1N2 antigens adsorbed with a plant origin nanoparticle adjuvant [Nano11–SwIAV] or in combination with a STING agonist ADU-S100 [NanoS100–SwIAV]. Conventional pigs were vaccinated via IN and challenged with a heterologous SwIAV H1N1-OH7 or 2009 H1N1 pandemic virus. Immunologically, in NanoS100–SwIAV vaccinates, we observed enhanced frequencies of activated monocytes in the blood of the pandemic virus challenged animals and in tracheobronchial lymph nodes (TBLN) of H1N1-OH7 challenged animals. In both groups of the virus challenged pigs, increased frequencies of IL-17A+ and CD49d+IL-17A+ cytotoxic lymphocytes were observed in Nano11–SwIAV vaccinates in the draining TBLN. Enhanced frequency of CD49d+IFNγ+ CTLs in the TBLN and blood of both the Nano11-based SwIAV vaccinates was ob...
Vaccines
The development of cross-protective vaccines against the zoonotic swine influenza A virus (swIAV)... more The development of cross-protective vaccines against the zoonotic swine influenza A virus (swIAV), a potential pandemic-causing agent, continues to be an urgent global health concern. Commercially available vaccines provide suboptimal cross-protection against circulating subtypes of swIAV, which can lead to worldwide economic losses and poor zoonosis deterrence. The limited efficacy of current swIAV vaccines demands innovative strategies for the development of next-generation vaccines. Considering that intramuscular injection is the standard route of vaccine administration in both human and veterinary medicine, the exploration of alternative strategies, such as intradermal vaccination, presents a promising avenue for vaccinology. This investigation demonstrates the first evaluation of a direct comparison between a commercially available multivalent swIAV vaccine and monovalent whole inactivated H1N2 swine influenza vaccine, delivered by intradermal, intranasal, and intramuscular rou...
Frontiers in Cellular and Infection Microbiology, Jul 1, 2021
A novel influenza viral vector based Brucella abortus vaccine (Flu-BA) was introduced for use in ... more 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
BioMed Research International, Nov 19, 2020
In this paper, we first used recombinant influenza viral vector (rIVV) subtype H5N1 expressing fr... more In this paper, we first used recombinant influenza viral vector (rIVV) subtype H5N1 expressing from the open reading frame of NS1 80 and NS1 124 amino acids of Brucella outer membrane proteins (Omp) 16 and 19, ribosomal L7/L12, and Cu-Zn superoxide dismutase (SOD) proteins to develop a human brucellosis vaccine. We made 18 combinations of IVVs in mono-, bi-, and tetravalent vaccine formulations and tested them on mice to select the safest and most effective vaccine samples. Then, the most effective vaccine candidates were further tested on guinea pigs. Safety of the rIVV-based vaccine candidate was evaluated by a mouse weight-gain test. Mice and guinea pigs were challenged with the virulent strain B. melitensis 16M. The protective effect of the rIVV-based vaccine candidate was assessed by quantitation of Brucella colonization in tissues and organs of challenged animals. All vaccine formulations were safe in mice. Tested vaccine formulations, as well as the commercial B. melitensis Rev.1 vaccine, have been found to protect mice from B. melitensis 16M infection within the range of 1.6 to 2.97 log 10 units (P < 0:05). Tetravalent vaccine formulations from the position of NS1 80 amino acids (0:2 ± 0:4), as well as the commercial B. melitensis Rev.1 vaccine (1:2 ± 2:6), have been found to protect guinea pigs from B. melitensis 16M infection at a significant level (P < 0:05). Thus, tetravalent vaccine formulation Flu-NS1-80-Omp16+Flu-NS1-80-L7/L12+Flu-NS1-80-Omp19+Flu-NS1-80-SOD was chosen as a potential vaccine candidate for further development of an effective human vaccine against brucellosis. These results show a promising future for the development of a safe human vaccine against brucellosis based on rIVVs.
Viruses, Apr 18, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Research Square (Research Square), Jan 21, 2021
Background: A new candidate vector vaccine against human brucellosis based on recombinant in uenz... more Background: A new candidate vector vaccine against human brucellosis based on recombinant in uenza viral vectors (rIVV) subtypes H5N1 expressing Brucella outer membrane protein (Omp) 16, L7/L12, Omp19 or Cu-Zn SOD proteins has been developed. This paper presents the results of the study of protection of the vaccine using on guinea pigs, including various options of administering, dose and frequency. Provided data of the novel vaccine candidate will contribute to its further movement into the preclinical stage study. Methods: General states of guinea pigs was assessed based on behavior and dynamics of a guinea pig weight-gain test. The effectiveness of the new anti-brucellosis vector vaccine was determined by studying its protective effect after conjunctival, intranasal and sublingual administration in doses 10 5 EID 50 , 10 6 EID 50 and 10 7 EID 50 during prime and boost vaccinations of animals, followed by challenge with a virulent strain of B. melitensis 16M infection. For sake of comparison, the commercial B. melitensis Rev.1 vaccine was used as a control. The protective properties of vaccines were assessed by quantitation of Brucella colonization in organs and tissues of infected animals and compared to the control groups. Results: It was observed a gradual increase in body weight of guinea pigs after prime and booster immunization with the vaccine using conjunctival, intranasal and sublingual routes of administration, as well as after using various doses of vaccine. The most optimal way of using the vaccine has been established: double intranasal immunization of guinea pigs at a dose of 10 6 EID 50 , which provides 80% protection of guinea pigs from B. melitensis 16M infection (P<0.05), which is comparable to the results of the effectiveness of the commercial B. melitensis Rev.1 vaccine. Conclusions: We developed effective vaccine candidate against brucellosis and developed its immunization protocol in guinea pig model. We believe that because of these studies, the proposed vaccine has achieved the best level of protection, which in turn provides a basis for its further promotion.
Medicina, Aug 1, 2018
Контакты: Турегелдиева Динара Алимхановна, заведующая лабораторией биологических моделей с вивари... more Контакты: Турегелдиева Динара Алимхановна, заведующая лабораторией биологических моделей с виварием (ЛБМ), РГП на ПХВ Казахский научный центр карантинных и зоонозных инфекций им. М. Айкимбаева (КНЦКЗИ). , г. Алматы, ул. Капальская, 14. Индекс 050054.
Journal of Nanobiotechnology, Dec 23, 2022
Journal of Nanobiotechnology
Background Swine influenza A viruses (SwIAVs) pose an economic and pandemic threat, and developme... more Background Swine influenza A viruses (SwIAVs) pose an economic and pandemic threat, and development of novel effective vaccines is of critical significance. We evaluated the performance of split swine influenza A virus (SwIAV) H1N2 antigens with a plant-derived nanoparticle adjuvant alone (Nano-11) [Nano11-SwIAV] or in combination with the synthetic stimulator of interferon genes (STING) agonist ADU-S100 (NanoS100-SwIAV). Specific pathogen free (SPF) pigs were vaccinated twice via intramuscular (IM) or intradermal (ID) routes and challenged with a virulent heterologous SwIAV H1N1-OH7 virus. Results Animals vaccinated IM or ID with NanoS100-SwIAV had significantly increased cross-reactive IgG and IgA titers in serum, nasal secretion and bronchoalveolar lavage fluid at day post challenge 6 (DPC6). Furthermore, NanoS100-SwIAV ID vaccinates, even at half the vaccine dose compared to their IM vaccinated counterparts, had significantly increased frequencies of CXCL10+ myeloid cells in the...
Viruses
Influenza A viruses (IAV-S) belonging to the H1 subtype are endemic in swine worldwide. Antigenic... more Influenza A viruses (IAV-S) belonging to the H1 subtype are endemic in swine worldwide. Antigenic drift and antigenic shift lead to a substantial antigenic diversity in circulating IAV-S strains. As a result, the most commonly used vaccines based on whole inactivated viruses (WIVs) provide low protection against divergent H1 strains due to the mismatch between the vaccine virus strain and the circulating one. Here, a consensus coding sequence of the full-length of HA from H1 subtype was generated in silico after alignment of the sequences from IAV-S isolates obtained from public databases and was delivered to pigs using the Orf virus (ORFV) vector platform. The immunogenicity and protective efficacy of the resulting ORFVΔ121conH1 recombinant virus were evaluated against divergent IAV-S strains in piglets. Virus shedding after intranasal/intratracheal challenge with two IAV-S strains was assessed by real-time RT-PCR and virus titration. Viral genome copies and infectious virus load w...
Journal of Immunology, May 1, 2022
Infectious Diseases of Poverty, 2021
Background A new candidate vector vaccine against human brucellosis based on recombinant influenz... more Background A new candidate vector vaccine against human brucellosis based on recombinant influenza viral vectors (rIVV) subtypes H5N1 expressing Brucella outer membrane protein (Omp) 16, L7/L12, Omp19 or Cu–Zn SOD proteins has been developed. This paper presents the results of the study of protection of the vaccine using on guinea pigs, including various options of administering, dose and frequency. Provided data of the novel vaccine candidate will contribute to its further movement into the preclinical stage study. Methods General states of guinea pigs was assessed based on behavior and dynamics of a guinea pig weight-gain test. The effectiveness of the new anti-brucellosis vector vaccine was determined by studying its protective effect after conjunctival, intranasal and sublingual administration in doses 10 5 EID 50 , 10 6 EID 50 and 10 7 EID 50 during prime and boost vaccinations of animals, followed by challenge with a virulent strain of B. melitensis 16 M infection. For sake of...
Advances in Animal and Veterinary Sciences, 2020
Moreover, the vaccine even in vaccinated horses provided a continuous protective immune response ... more Moreover, the vaccine even in vaccinated horses provided a continuous protective immune response against the homologous wild-type virus A/equine/Otar/764/2007 (H3N8) with a duration of 12 months (Tabynov et al.,
A novel influenza viral vector based Brucella abortus vaccine (Flu-BA) was introduced for use in ... more 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 exper...
International Professional Journal "Medicine", Aug 1, 2018
Контакты: Турегелдиева Динара Алимхановна, заведующая лабораторией биологических моделей с вивари... more Контакты: Турегелдиева Динара Алимхановна, заведующая лабораторией биологических моделей с виварием (ЛБМ), РГП на ПХВ Казахский научный центр карантинных и зоонозных инфекций им. М. Айкимбаева (КНЦКЗИ). , г. Алматы, ул. Капальская, 14. Индекс 050054.
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Papers by Dina Bugybayeva