Vaccination with recombinant Semliki Forest virus particles expressing translation initiation factor 3 of Brucella abortus induces protective immunity in BALB/c mice

Cabrera, Alex; Sáez, Darwin; Céspedes, Sandra; Andrews, Edilia; Oñate, Ángel

doi:10.1016/j.imbio.2008.11.016

Cited by 33 publications

(22 citation statements)

References 45 publications

(57 reference statements)

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“…To date, Escherichia coli [21], Salmonella enterica [22], Ochrobactrum anthropi [23] and Semliki Forest virus (SFV) [24] have been used as vectors for expressing Brucella proteins in vivo . It has been shown that the tested bacterial (intracellular) and viral vectors are capable of infecting a wide range of cell types and expressing Brucella antigens within the infected cells.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Tabynov¹,

Sansyzbay²,

Kydyrbayev³

et al. 2014

Virol J

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BackgroundWe 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 ResultsFour 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.ConclusionThus, influenza vectors expressing Brucella protective antigens can be developed as novel influenza vectored vaccine against B. abortus infection.

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Section: Introductionmentioning

confidence: 99%

“…It has been shown that the tested bacterial (intracellular) and viral vectors are capable of infecting a wide range of cell types and expressing Brucella antigens within the infected cells. Furthermore, in all cases, Th1 CD4 + and CD8 + T-cell anti-brucellosis immune responses were elicited in immunized animals [21-24]. …”

Section: Introductionmentioning

confidence: 99%

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

Tabynov¹,

Sansyzbay²,

Kydyrbayev³

et al. 2014

Virol J

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“…In an effort to create an effective and safe vaccine against B. abortus, several research groups have developed subunit (recombinant proteins) [4][5][6][7][8][9][10][11][12], a DNA [13][14][15][16][17][18], or live vector vaccines (based on bacteria and viruses) [19][20][21][22]. All of these vaccines were safe when tested in animal models (laboratory mice), and some when tested in cattle.…”

Section: Introductionmentioning

confidence: 99%

Safety of the novel vector vaccine against Brucella abortus based on recombinant influenza viruses expressing Brucella L7/L12 and OMP16 proteins, in cattle

Tabynov¹,

Kydyrbayev²,

Ryskeldinova³

et al. 2014

J Vaccines Immunol

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Citation: Tabynov K, Kydyrbayev Z, Ryskeldinova S, Yespembetov B, Syrymkyzy N, et al. (2015) eertechz AbstractThis paper presents the results of a study of the safety of new vector vaccine against B. abortus based on recombinant influenza A subtype H5N1 or H1N1 (viral constructs vaccine formulation) viruses expressing Brucella ribosomal protein L7/L12 and Omp16, in cattle. To increase the effectiveness of the vaccine, adjuvants such as Montanide Gel01 or chitosan were included in its composition. Immunization of cattle (5 animals per group) with the viral constructs vaccine formulation only, or its combination with adjuvants Montanide Gel01 or chitosan, were conducted via the conjunctival method using cross prime (influenza virus subtype H5N1) and booster (influenza virus subtype H1N1) vaccination schedules. Vaccine candidates were evaluated in comparison with the positive (B. abortus S19) and negative (PBS) controls. Comprehensive studies involving thermometry and clinical examination, hematology and biochemical blood analysis, showed that all of the viral constructs vaccine formulation, as well as their combination with adjuvants, compared to the commercial bacterial vaccine B. abortus S19 were completely safe in cattle. Furthermore it is shown that the developed vaccines can effectively differentiate vaccinated animals from infected animals. Brucella L7/L12 or Omp16 proteins. The influenza A virus contains a segmented genome consisting of eight negative-strand RNA fragments. Of these, the smallest fragment (NS) -encoding two proteins: viral nonstructural protein (NS1) and nuclear export protein (Nep) -is a convenient target for genetic manipulation as NS1 is able to tolerate foreign sequences exceeding its own length [25]. Thus, the ORF of NS1 was used for inserting Brucella sequences in this study. The А/Puerto Rico/8/34 (H1N1) strain was used as the backbone for obtaining influenza A virus vectors expressing Brucella L7/L12 or Omp16 sequences in the form of fusion proteins with the N-terminal 124 amino acid residues of NS1.Our previous studies have shown that a bivalent vaccine formulation comprising a mixture of recombinant influenza A virus subtype H5N1 or H1N1 expressing the ribosomal L7/L12 or Omp16 proteins in prime and booster immunization mode (via conjunctival injection) in cattle induced a strong antigen-specific T-cell immune response, and most importantly provided a high level of protectiveness comparable to the commercial B. abortus S19 vaccine and superior to the B. abortus S19 vaccine in combination with Montanide Gel01 adjuvant [24]. Based on this, the next stage of our study was to evaluate the safety of the proposed new live vector vaccine in cattle. Additionally, we evaluated the possibility of differentiating infected animals from vaccinated animals using the developed vaccine.

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“…Co-expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced the immune response. Replication-deficient SFV particles carrying the Brucella abortus translation initiation factor 3 (IF3) were subjected to immunization studies in BALB/c mice, which resulted in protection against challenges with the virulent B. abortus strain 2308 [71]. In another study, SIN vectors were utilized for the expression of the protective antigen (PA) for Bacillus antracis in Swiss Webster mice leading to the generation of specific and neutralizing antibodies and partial protection against challenges with pathogenic bacteria [72].…”

Section: Self-replicating Rna Virus-based Vaccinesmentioning

confidence: 99%

Replicon RNA Viral Vectors as Vaccines

Lundström¹

2016

Vaccines

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Single-stranded RNA viruses of both positive and negative polarity have been used as vectors for vaccine development. In this context, alphaviruses, flaviviruses, measles virus and rhabdoviruses have been engineered for expression of surface protein genes and antigens. Administration of replicon RNA vectors has resulted in strong immune responses and generation of neutralizing antibodies in various animal models. Immunization of mice, chicken, pigs and primates with virus-like particles, naked RNA or layered DNA/RNA plasmids has provided protection against challenges with lethal doses of infectious agents and administered tumor cells. Both prophylactic and therapeutic efficacy has been achieved in cancer immunotherapy. Moreover, recombinant particles and replicon RNAs have been encapsulated by liposomes to improve delivery and targeting. Replicon RNA vectors have also been subjected to clinical trials. Overall, immunization with self-replicating RNA viruses provides high transient expression levels of antigens resulting in generation of neutralizing antibody responses and protection against lethal challenges under safe conditions.

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Vaccination with recombinant Semliki Forest virus particles expressing translation initiation factor 3 of Brucella abortus induces protective immunity in BALB/c mice

Cited by 33 publications

References 45 publications

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

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

Safety of the novel vector vaccine against Brucella abortus based on recombinant influenza viruses expressing Brucella L7/L12 and OMP16 proteins, in cattle

Replicon RNA Viral Vectors as Vaccines

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