Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Virology Journal
Published in: Virology Journal 1/2014

Open Access 01-12-2014 | Research

Influenza viral vectors expressing the Brucella OMP16 or L7/L12 proteins as vaccines against B. abortus infection

Authors: Kaissar Tabynov, Abylai Sansyzbay, Zhailaubay Kydyrbayev, Bolat Yespembetov, Sholpan Ryskeldinova, Nadezhda Zinina, Nurika Assanzhanova, Kulaisan Sultankulova, Nurlan Sandybayev, Berik Khairullin, Irina Kuznetsova, Boris Ferko, Andrej Egorov

Published in: Virology Journal | Issue 1/2014

Login to get access

Abstract

Background

We generated novel, effective candidate vaccine against Brucella abortus based on recombinant influenza viruses expressing the Brucella ribosomal protein L7/L12 or outer membrane protein (Omp)-16 from the NS1 open reading frame. The main purpose of this work was to evaluate the safety, immunogenicity and protectiveness of vaccine candidate in laboratory animals.

Methods and Results

Four recombinant influenza A viral constructs of the subtypes Н5N1 or H1N1 expressing the Brucella proteins L7/L12 or Omp16 were obtained by a reverse genetics method: Flu-NS1-124-L7/L12-H5N1, Flu-NS1-124-Omp16-H5N1, Flu-NS1-124-L7/L12-H1N1 and Flu-NS1-124-Omp16-H1N1. Despite of substantial modification of NS1 gene, all constructs replicated well and were retain their Brucella inserts over five passages in embryonated chicken eggs (CE). Administration of the mono- or bivalent vaccine formulation via prime-boost intranasal (i.n.), conjunctival (c.) or subcutaneous (s.c.) immunization was safe in mice; no deaths, body weight loss or pathomorphological changes were observed over 56 days. Moreover, guinea pigs vaccinated i.n. with vaccine vectors did not shed the vaccine viruses through their upper respiratory tract after the prime and booster vaccination. These findings confirmed the replication-deficient phenotype of viral vectors. The highest antibody response to Brucella antigen was obtained with constructs expressing L7/L12 (ELISA, GMT 242.5-735.0); whereas the highest T-cell immune response- with construct expressing Omp16 (ELISPOT, 337 ± 52-651 ± 45 spots/4×105cells), which was comparable (P > 0.05) to the response induced by the commercial vaccine B. abortus 19. Interestingly, c. immunization appeared to be optimal for eliciting T-cell immune response. In guinea pigs, the highest protective efficacy after challenge with B. abortus 544 was achieved with Omp16 expressing constructs in both monovalent or bivalent vaccine formulations; protective efficacy was comparable to those induced by a commercial live B. abortus 19 vaccine.

Conclusion

Thus, influenza vectors expressing Brucella protective antigens can be developed as novel influenza vectored vaccine against B. abortus infection.
Appendix
Available only for authorised users
Literature
1.
Godfroid J, Cloeckaert A, Liautard JP, Kohler S, Fretin D, Walravens K, Garin-Bastuji B, Letesson JJ: From the discovery of the Malta fever’s agent to the discovery of a marine mammal reservoir, brucellosis has continuously been a re-emerging zoonosis. Vet Res 2005, 36: 313-326. 10.1051/vetres:2005003PubMedCrossRef
2.
Schurig GG, Sriranganathan N, Corbel MJ: Brucellosis vaccines: past, present and future. Vet Microbiol 2002, 90: 479-496. 10.1016/S0378-1135(02)00255-9PubMedCrossRef
3.
Ashford DA, di Pietra J, Lingappa J, Woods C, Noll H, Neville B, Weyant R, Bragg SL, Spiegel RA, Tappero J, Perkins BA: Adverse events in humans associated with accidental exposure to the livestock brucellosis vaccine RB51. Vaccine 2004, 22: 3435-3439. 10.1016/j.vaccine.2004.02.041PubMedCrossRef
4.
5.
Oliveira SC, Splitter GA: CD8 + type 1 CD44hi CD45 RBloT lymphocytes control intracellular Brucella abortus infection as demonstrated in major histocompatibility complex class I- and class II-deficient mice. Eur J Immunol 1995, 25: 2551-2557. 10.1002/eji.1830250922PubMedCrossRef
6.
Al-Mariri A, Tibor A, Mertens P, De Bolle X, Michel P, Godefroid J, Walravens K, Letesson JJ: Protection of BALB/c mice against Brucella abortus 544 challenge by vaccination with bacterioferritin or P39 recombinant proteins with CpGoligodeoxynucleotides as adjuvant. Infect Immun 2001, 69: 4816-4822. 10.1128/IAI.69.8.4816-4822.2001PubMedPubMedCentralCrossRef
7.
Tabatabai LB, Pugh GW Jr: Modulation of immune responses in Balb/c mice vaccinated with Brucellaabortus Cu-Zn superoxide dismutase synthetic peptide vaccine. Vaccine 1994, 12: 919-924. 10.1016/0264-410X(94)90035-3PubMedCrossRef
8.
Oliveira SC, Splitter GA: Immunization of mice with recombinant L7/L12 ribosomal protein confers protection against Brucella abortus infection. Vaccine 1996, 14: 959-962. 10.1016/0264-410X(96)00018-7PubMedCrossRef
9.
Oliveira SC, Zhu Y, Splitter G: Sequences of the rplJL operon containing the L10 and L7/L12 genes from Brucella abortus. Gene 1994, 140: 137-138. 10.1016/0378-1119(94)90744-7PubMedCrossRef
10.
Oliveira SC, Zhu Y, Splitter GA: Recombinant L7/L12 ribosomal protein and gamma-irradiated Brucella abortus induce a T-helper 1 subset response from murine CD4+ T cells. Immunology 1994, 83: 659-664.PubMedPubMedCentral
11.
Oliveira SC, Harms JS, Banai M, Splitter GA: Recombinant Brucella abortus proteins that induce proliferation and gamma-interferon secretion by CD4+ T cells from Brucella-vaccinated mice and delayed-type hypersensitivity in sensitized guinea pigs. Cell Immunol 1996, 172: 262-268. 10.1006/cimm.1996.0241PubMedCrossRef
12.
Cassataro J, Estein SM, Pasquevich KA, Velikovsky CA, de laBarrera S, Bowden R, Fossati CA, Giambartolomei GH: Vaccination with the recombinant Brucella outer membrane protein 31 or a derived 27-amino-acid synthetic peptide elicits a CD4+ T helper 1 response that protects against Brucella melitensis infection. Infect Immun 2005, 73: 8079-8088. 10.1128/IAI.73.12.8079-8088.2005PubMedPubMedCentralCrossRef
13.
Pasquevich KA, Estein SM, García Samartino C, Zwerdling A, Coria LM, Barrionuevo P, Fossati CA, Giambartolomei GH, Cassataro J: Immunization with recombinant Brucella species outer membrane protein Omp16 or Omp19 in adjuvant induces specific CD4+ and CD8+ T cells as well as systemic and oral protection against Brucella abortus infection. Infect Immun 2009, 77: 436-445. 10.1128/IAI.01151-08PubMedPubMedCentralCrossRef
14.
Mallick AI, Singha H, Chaudhuri P, Nadeem A, Khan SA, Dar KA, Owais M: Liposomised recombinant ribosomal L7/L12 protein protects BALB/c mice against Brucella abortus 544 infection. Vaccine 2007, 25: 3692-3704. 10.1016/j.vaccine.2007.01.066PubMedCrossRef
15.
Leclercq S, Harms JS, Oliveira SC: Enhanced efficacy of DNA vaccines against an intracellular bacterial pathogen by genetic adjuvants. Curr Pharm Biotechnol 2003, 4: 99-107. 10.2174/1389201033489892PubMedCrossRef
16.
Kurar E, Splitter GA: Nucleic acid vaccination of Brucella abortus ribosomal L7/L12 gene elicits immune response. Vaccine 1997, 15: 1851-1857. 10.1016/S0264-410X(97)00140-0PubMedCrossRef
17.
Oñate AA, Céspedes S, Cabrera A, Rivers R, González A, Muñoz C, Folch H, Andrews E: A DNA vaccine encoding Cu, Zn superoxide dismutase of Brucella abortus induces protective immunity in BALB/c mice. Infect Immun 2003, 71: 4857-4861. 10.1128/IAI.71.9.4857-4861.2003PubMedPubMedCentralCrossRef
18.
Mayfield JE, Bricker BJ, Godfrey H, Crosby RM, Knight DJ, Halling SM, Balinsky D, Tabatabai LB: The cloning, expression, and nucleotide sequence of a gene coding for an immunogenic Brucella abortus protein. Gene 1988, 63: 1-9. 10.1016/0378-1119(88)90540-9PubMedCrossRef
19.
Cassataro J, Velikovsky CA, de la Barrera S, Estein SM, Bruno L, Bowden R, Pasquevich KA, Fossati CA, Giambartolomei GH: A DNA vaccine coding for the Brucella outer membrane protein 31 confers protection against B. melitensis and B. ovis infection by eliciting a specific cytotoxic response. Infect Immun 2005, 73: 6537-6546. 10.1128/IAI.73.10.6537-6546.2005PubMedPubMedCentralCrossRef
20.
Luo D, Ni B, Li P, Shi W, Zhang S, Han Y, Mao L, He Y, Wu Y, Wang X: Protective immunity elicited by a divalent DNA vaccine encoding both the L7/L12 and Omp16 genes of Brucella abortus in BALB/c mice. Infect Immun 2006, 74: 2734-2741. 10.1128/IAI.74.5.2734-2741.2006PubMedPubMedCentralCrossRef
21.
Harms JS, Durward MA, Magnani DM, Splitter GA: Evaluation of recombinant invasive, non-pathogenic Eschericia coli as a vaccine vector against the intracellular pathogen. J Immune Based Ther Vaccines 2009, 7: 1. doi:10.1186/1476-8518-7-1 10.1186/1476-8518-7-1PubMedPubMedCentralCrossRef
22.
Zhao Z, Li M, Luo D, Xing L, Wu S, Duan Y, Yang P, Wang X: Protection of mice from Brucella infection by immunization with attenuated Salmonella enteric serovar typhimurium expressing A L7/L12 and BLS fusion antigen of Brucella. Vaccine 2009, 27: 5214-5219. 10.1016/j.vaccine.2009.06.075PubMedCrossRef
23.
He Y, Vemulapalli R, Schurig GG: Recombinant Ochrobactrum anthropi Expressing Brucella abortus Cu, Zn Superoxide Dismutase Protects Mice against B. abortus Infection Only after Switching of Immune Responses to Th1 Type. Infect Immun 2002,70(5):2535-2543. 10.1128/IAI.70.5.2535-2543.2002PubMedPubMedCentralCrossRef
24.
Cabrera A, Sáez D, Céspedes S, Andrews E, Oñate A: Vaccination with recombinant Semliki Forest virus particles expressing translation initiation factor 3 of Brucella abortus induces protective immunity in BALB/c mice. Immunobiology 2009,214(6):467-474. 10.1016/j.imbio.2008.11.016PubMedCrossRef
25.
Neumann G, Watanabe T, Ito H, Watanabe S, Goto H, Gao P, Hughes M, Perez DR, Donis R, Hoffmann E, Hobom G, Kawaoka Y: Generation of influenza A viruses entirely from cloned cDNAs. Proc Natl Acad Sci U S A 1999, 96: 9345-9350. 10.1073/pnas.96.16.9345PubMedPubMedCentralCrossRef
26.
Pleschka S, Jaskunas R, Engelhardt OG, Zurcher T, Palese P, Garcia-Sastre A: A plasmid-based reverse genetics system for influenza A virus. J Virol 1996, 70: 4188-4192.PubMedPubMedCentral
27.
Kittel C, Sereinig S, Ferko B, Stasakova J, Romanova J, Wolkerstorfer A, Katinger H, Egorov A: Rescue of influenza virus expressing GFP from the NS1 reading frame. Virology 2004, 324: 67-73. 10.1016/j.virol.2004.03.035PubMedCrossRef
28.
29.
Cruickshank JC: The duration of bacteraemia in relation to the virulence of Brucella strains. J Hyg (Lond) 1957,55(1):140-147. 10.1017/S0022172400061313CrossRef
30.
Gerdts V, Mutwiri GK, Tikoo SK, Babiuk LA: Mucosal delivery of vaccines in domestic animals. Vet Res 2006, 37: 487-510. 10.1051/vetres:2006012PubMedCrossRef
31.
Campbell CH, Easterday BC, Webster RG: Strains of Hong Kong influenza virus in calves. J Infect Dis 1977, 135: 678-680. 10.1093/infdis/135.4.678PubMedCrossRef
32.
Brown IH, Crawshaw TR, Harris PA, Alexander DJ: Detection of antibodies to influenza A virus in cattle in association with respiratory disease and reduced milk yield. Vet Rec 1998, 143: 637-638.PubMed
33.
Gunning RF, Brown IH, Crawshaw TR: Evidence of influenza A virus infection in dairy cows with sporadic milk drop syndrome. Vet Rec 1999, 145: 556-557. 10.1136/vr.145.19.556PubMedCrossRef
34.
Graham DA, Calvert V, McLaren E: Retrospective analysis of serum and nasal mucus from cattle in Northern Ireland for evidence of infection with influenza A virus. Vet Rec 2002, 150: 201-204. 10.1136/vr.150.7.201PubMedCrossRef
35.
Sereinig S, Stukova M, Zabolotnyh N, Ferko B, Kittel C, Romanova J, Vinogradova T, Katinger H, Kiselev O, Egorov A: Influenza virus NS Vectors expressing the mycobacterium tuberculosis ESAT-6 Protein Induce CD4+ Th1 immune response and protect animals against tuberculosis challenge. Clin Vaccine Immunol 2006,13(8):898-904. 10.1128/CVI.00056-06PubMedPubMedCentralCrossRef
36.
Ferko B, Stasakova J, Sereinig S, Romanova J, Katinger D, Niebler B, Katinger H, Egorov A: Hyperattenuated recombinant influenza A virus nonstructural-protein-encoding vectors induce human immunodeficiency virus type 1 Nef-specific systemic and mucosal immune responses in mice. J Virol 2001, 75: 8899-8908. 10.1128/JVI.75.19.8899-8908.2001PubMedPubMedCentralCrossRef
37.
el Idrissi AH, Benkirane A, el Maadoudi M, Bouslikhane M, Berrada J, Zerouali A: Comparison of the efficacy of Brucella abortus strain RB51 and Brucella melitensis Rev. 1 live vaccines against experimental infection with Brucella melitensis in pregnant ewes. Rev Sci Tech 2001,20(3):741-747.PubMed
38.
Egorov A, Brandt S, Sereinig S, Romanova J, Ferko B, Katinger D, Grassauer A, Alexandrova G, Katinger H, Muster T: Transfectant influenza A viruses with long deletions in the NS1 protein grow efficiently in vero cells. J Virol 1998,72(8):6437-6441.PubMedPubMedCentral
39.
Wang X, Basler CF, Williams BR, Silverman RH, Palese P, Garcia-Sastre A: Functional replacement of the carboxy-terminal two-thirds of the influenza A virus NS1 protein with short heterologous dimerization domains. J Virol 2002, 76: 12951-12962. 10.1128/JVI.76.24.12951-12962.2002PubMedPubMedCentralCrossRef
40.
Romanova J, Krenn BM, Wolschek M, Ferko B, Romanovskaja-Romanko E, Morokutti A, Shurygina A-P, Nakowitsch S, Ruthsatz T, Kiefmann B, König U, Bergmann M, Sachet M, Balasingam S, Mann A, Oxford J, Slais M, Kiselev O, Muster T, Egorov A: Preclinical evaluation of a replication-deficient intranasal ΔNS1 H5N1 influenza vaccine. PLoS One 2009,4(6):e5984. doi:10.1371/journal.pone.0005984 10.1371/journal.pone.0005984PubMedPubMedCentralCrossRef
41.
Wacheck V, Egorov A, Groiss F, Pfeiffer A, Fuereder T, Hoeflmayer D, Kundi M, Popow-Kraupp T, Redlberger-Fritz M, Mueller CA, Cinatl J, Michaelis M, Geiler J, Bergmann M, Romanova J, Roethl E, Morokutti A, Wolschek M, Ferko B, Seipelt J, Dick-Gudenus R, Muster T: A novel type of influenza vaccine: safety and immunogenicity of replication-deficient influenza virus created by deletion of the interferon antagonist NS1. J Infect Dis 2010,201(3):354-362. doi: 10.1086/649428 10.1086/649428PubMedCrossRef
42.
43.
Steven P, Gebert A: Conjunctiva-associated lymphoid tissue – current knowledge, animal models and experimental prospects. Ophthalmic Res 2009, 42: 2-8. 10.1159/000219678PubMedCrossRef
44.
Kageyama M, Nakatsuka K, Yamaguchi T, Owen RL, Shimada T: Ocular defense mechanisms with special reference to the demonstration and functional morphology of the conjunctiva-associated lymphoid tissue in Japanese monkeys. Arch Histol Cytol 2006, 69: 311-322. 10.1679/aohc.69.311PubMedCrossRef
45.
Belser JA, Zeng H, Katz JM, Tumpey TM: Ocular tropism of influenza A viruses: identification of H7 subtype-specific host responses in human respiratory and ocular cells. J Virol 2011,85(19):10117-10125. 10.1128/JVI.05101-11PubMedPubMedCentralCrossRef
46.
Pasquevich KA, García Samartino C, Coria LM, Estein SM, Zwerdling A, Ibañez AE, Barrionuevo P, Oliveira FS, Carvalho NB, Borkowski J, Oliveira SC, Warzecha H, Giambartolomei GH, Cassataro J: The protein moiety of outer membrane protein 16 is a new bacterial pathogen-associated molecular pattern that activates dendritic cells in vivo, induces a th1 immune response, and is a promising self-adjuvanting vaccine against systemic and oral acquired Brucellosis. J Immunol 2010,184(9):5200-5212. doi:10.4049/jimmunol.0902209 10.4049/jimmunol.0902209PubMedCrossRef
47.
Tabynov K, Kydyrbayev Z, Ryskeldinova S, Yespembetov B, Zinina N, Assanzhanova N, Kozhamkulov Y, Inkarbekov D, Gotskina T, Sansyzbay A: Novel influenza virus vectors expressing Brucella L7/L12 or Omp16 proteins in cattle induce a strong T-cell immune response, as well as high protectiveness against B. abortus infection. Vaccine 2014, 32: 2034-2041. 10.1016/j.vaccine.2014.02.058PubMedCrossRef
48.
Hoffmann E, Neumann G, Kawaoka Y, Hobom G, Webster RG: A DNA transfection system for generation of influenza A virus from eight plasmids. Proc Natl Acad Sci U S A 2000, 97: 6108-6113. 10.1073/pnas.100133697PubMedPubMedCentralCrossRef
49.
Chervyakova OV, Strochkov VM, Sultankulova KT, Sandybayev NT, Zaitsev VL, Mamadaliyev SM: Molecular and genetic analysis of NS gene from high pathogenic strains of the avian influenza (H5N1) virus isolated in Kazakhstan. Gene 2011, 476: 15-19. 10.1016/j.gene.2011.02.003PubMedCrossRef
50.
51.
Reed LJ, Muench H: A simple method of estimating fifty percent endpoints. Am J Hyg 1938, 27: 493-497.
Metadata
Title
Influenza viral vectors expressing the Brucella OMP16 or L7/L12 proteins as vaccines against B. abortus infection
Authors
Kaissar Tabynov
Abylai Sansyzbay
Zhailaubay Kydyrbayev
Bolat Yespembetov
Sholpan Ryskeldinova
Nadezhda Zinina
Nurika Assanzhanova
Kulaisan Sultankulova
Nurlan Sandybayev
Berik Khairullin
Irina Kuznetsova
Boris Ferko
Andrej Egorov
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2014
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-11-69

Other articles of this Issue 1/2014

Virology Journal 1/2014 Go to the issue

Research

Mouse Cytomegalovirus infection overrules T regulatory cell suppression on natural killer cells

Research

Studies of inactivation mechanism of non-enveloped icosahedral virus by a visible ultrashort pulsed laser

Research

Comparison of multiple DNA vaccines for protection against cytomegalovirus infection in BALB/c mice

Research

Nonstructural proteins 2C and 3D are involved in autophagy as induced by the encephalomyocarditis virus

Research

High prevalence and diversity of species D adenoviruses (HAdV-D) in human populations of four Sub-Saharan countries

Research

Type-I interferon response affects an inoculation dose-independent mortality in mice following Japanese encephalitis virus infection

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits