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Influenza viral vectors expressing the Brucella OMP16 or L7/L12 proteins as vaccines against B. abortus infection.
Virol J. 2014 Apr 10; 11:69.VJ

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.

Authors+Show Affiliations

The Research Institute for Biological Safety Problems, Zhambulskaya oblast, Kordaiskiy rayon, Gvardeisky, Republic of Kazakhstan. tabynov_81@mail.ru.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24716528

Citation

Tabynov, Kaissar, et al. "Influenza Viral Vectors Expressing the Brucella OMP16 or L7/L12 Proteins as Vaccines Against B. Abortus Infection." Virology Journal, vol. 11, 2014, p. 69.
Tabynov K, Sansyzbay A, Kydyrbayev Z, et al. Influenza viral vectors expressing the Brucella OMP16 or L7/L12 proteins as vaccines against B. abortus infection. Virol J. 2014;11:69.
Tabynov, K., Sansyzbay, A., Kydyrbayev, Z., Yespembetov, B., Ryskeldinova, S., Zinina, N., Assanzhanova, N., Sultankulova, K., Sandybayev, N., Khairullin, B., Kuznetsova, I., Ferko, B., & Egorov, A. (2014). Influenza viral vectors expressing the Brucella OMP16 or L7/L12 proteins as vaccines against B. abortus infection. Virology Journal, 11, 69. https://doi.org/10.1186/1743-422X-11-69
Tabynov K, et al. Influenza Viral Vectors Expressing the Brucella OMP16 or L7/L12 Proteins as Vaccines Against B. Abortus Infection. Virol J. 2014 Apr 10;11:69. PubMed PMID: 24716528.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Influenza viral vectors expressing the Brucella OMP16 or L7/L12 proteins as vaccines against B. abortus infection. AU - Tabynov,Kaissar, AU - Sansyzbay,Abylai, AU - Kydyrbayev,Zhailaubay, AU - Yespembetov,Bolat, AU - Ryskeldinova,Sholpan, AU - Zinina,Nadezhda, AU - Assanzhanova,Nurika, AU - Sultankulova,Kulaisan, AU - Sandybayev,Nurlan, AU - Khairullin,Berik, AU - Kuznetsova,Irina, AU - Ferko,Boris, AU - Egorov,Andrej, Y1 - 2014/04/10/ PY - 2014/02/22/received PY - 2014/04/04/accepted PY - 2014/4/11/entrez PY - 2014/4/11/pubmed PY - 2014/9/13/medline SP - 69 EP - 69 JF - Virology journal JO - Virol. J. VL - 11 N2 - 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. SN - 1743-422X UR - https://www.unboundmedicine.com/medline/citation/24716528/Influenza_viral_vectors_expressing_the_Brucella_OMP16_or_L7/L12_proteins_as_vaccines_against_B__abortus_infection_ L2 - https://virologyj.biomedcentral.com/articles/10.1186/1743-422X-11-69 DB - PRIME DP - Unbound Medicine ER -