Modified Vaccinia virus Ankara: Innate immune activation and induction of cellular signalling

Price, Philip J. R.; Torres-Domínguez, Lino E.; Brandmüller, Christine; Sutter, Gerd; Lehmann, Michael H.

doi:10.1016/j.vaccine.2013.03.017

Cited by 47 publications

(33 citation statements)

References 38 publications

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“…Activation of C5 independently of C3 has been observed during cerebral malaria infection, in which it makes a critical contribution to the development of disease (26). We discovered that C5 functions independently of C3 to induce early neutrophil recruitment during infection with MVA, a nonreplicating viral vector known to activate the innate immune system (27). C5 may be activated by proteolytic enzymes such as serine proteases released from phagocytic cells (21), as we observed no differences in C3-deficient mice treated with antithrombin III (data not shown), ruling out thrombin-mediated activation (25).…”

Section: Discussionmentioning

confidence: 92%

Complement Component C5 Recruits Neutrophils in the Absence of C3 during Respiratory Infection with Modified Vaccinia Virus Ankara

Price

Bánki

Scheideler

et al. 2015

The Journal of Immunology

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Efficient leukocyte migration is important for an effective host response to viral infection and the development of adaptive immunity. The poxvirus strain modified vaccinia virus Ankara (MVA), a safe and efficient viral vector, rapidly induces chemokine expression and respiratory recruitment of leukocytes, which is unique among vaccinia viruses. In addition to chemokines, the complement system contributes to the attraction and activation of different types of leukocytes. Using a murine model of intranasal infection, we show in this study that MVA-induced neutrophil recruitment depends on complement component C5. Remarkably, we find that C5 mediates neutrophil recruitment to the lung, even in the absence of the central complement component C3. Our findings argue for complement C5 activation during MVA infection of the lung via a C3-independent pathway, which enables rapid recruitment of neutrophils.

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Section: Discussionmentioning

confidence: 92%

Complement Component C5 Recruits Neutrophils in the Absence of C3 during Respiratory Infection with Modified Vaccinia Virus Ankara

Price

Bánki

Scheideler

et al. 2015

The Journal of Immunology

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“…Intranasal inoculation is an attractive route of vaccination for delivery of MVA to mucosal tissue in the respiratory tract, which was found to be both safe and immunogenic in a phase I clinical trial [1]. A distinguishing feature of MVA is its ability to activate a robust innate immune response [2-4]. We recently showed that MVA triggers the production of chemokines in primary lung fibroblasts and bone marrow derived macrophages (BMDM) which induce chemotaxis of neutrophils [5].…”

Section: Resultsmentioning

confidence: 99%

Modified Vaccinia virus Ankara but not vaccinia virus induces chemokine expression in cells of the monocyte/macrophage lineage

Lehmann

Price

Brandmüller

et al. 2015

Virol J

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BackgroundThe orthopoxvirus strain Modified Vaccinia virus Ankara (MVA) rapidly induces innate immune responses. Previously, we demonstrated that CCL2 and CCR1 are important players in MVA induced recruitment of leukocytes to the lung. Alveolar macrophages are sentinel cells in the lung, which are likely amongst the first cells of the immune system to encounter and respond to virus during respiratory infection. Therefore we examined the potential of the murine alveolar macrophage MH-S cell line as a model to study chemokine expression during infection with MVA and vaccinia virus (VACV) strain Western Reserve (WR).FindingsMVA but not VACV infected MH-S cells increased the expression of the CXCR2 acting chemokine CXCL2. MH-S cells constitutively produced CCL2 and CCR1 acting chemokines CCL3, CCL5 and CCL9. Consequently, supernatants of mock treated and virus infected MH-S cells induced chemotaxis of murine promyelocyte MPRO cells and human monocytic THP-1 cells at the same level. However, supernatants of MVA infected MH-S cells significantly increased chemotaxis of the CCR2 deficient human monocytic cell line U-937. Chemotaxis of all three cell types was inhibited by J 113863, a CCR1 antagonist. Additionally, we show that MVA but not VACV WR infection of THP-1 cells induces expression of C-C motif and C-X-C motif chemokines and generates a chemotactic activity for monocytes, which was J 113863 sensitive.ConclusionsThese results extend our previous findings, demonstrating that MVA but not VACV WR induces chemokine production in alveolar macrophages and monocytes, which can induce recruitment of monocytes in a CCR1 dependent manner.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-015-0252-1) contains supplementary material, which is available to authorized users.

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“…ϩ T cells via innate immune activations (39). In future studies, we will evaluate the protective efficacy of the H5M antigen as a recombinant protein without the MVA vector.…”

Section: Discussionmentioning

confidence: 99%

Broad Protection against Avian Influenza Virus by Using a Modified Vaccinia Ankara Virus Expressing a Mosaic Hemagglutinin Gene

Kamlangdee

Kingstad-Bakke

Anderson

et al. 2014

J Virol

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A critical failure in our preparedness for an influenza pandemic is the lack of a universal vaccine. Influenza virus strains diverge by 1 to 2% per year, and commercially available vaccines often do not elicit protection from one year to the next, necessitating frequent formulation changes. This represents a major challenge to the development of a cross-protective vaccine that can protect against circulating viral antigenic diversity. We have constructed a recombinant modified vaccinia virus Ankara (MVA) that expresses an H5N1 mosaic hemagglutinin (H5M) (MVA-H5M). This mosaic was generated in silico using 2,145 field-sourced H5N1 isolates. A single dose of MVA-H5M provided 100% protection in mice against clade 0, 1, and 2 avian influenza viruses and also protected against seasonal H1N1 virus (A/Puerto Rico/8/34). It also provided short-term (10 days) and long-term (6 months) protection postvaccination. Both neutralizing antibodies and antigen-specific CD4 ؉ and CD8 ؉ T cells were still detected at 5 months postvaccination, suggesting that MVA-H5M provides long-lasting immunity. IMPORTANCEInfluenza viruses infect a billion people and cause up to 500,000 deaths every year. A major problem in combating influenza is the lack of broadly effective vaccines. One solution from the field of human immunodeficiency virus vaccinology involves a novel in silico mosaic approach that has been shown to provide broad and robust protection against highly variable viruses. Unlike a consensus algorithm which picks the most frequent residue at each position, the mosaic method chooses the most frequent Tcell epitopes and combines them to form a synthetic antigen. These studies demonstrated that a mosaic influenza virus H5 hemagglutinin expressed by a viral vector can elicit full protection against diverse H5N1 challenges as well as induce broader immunity than a wild-type hemagglutinin.

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Modified Vaccinia virus Ankara: Innate immune activation and induction of cellular signalling

Cited by 47 publications

References 38 publications

Complement Component C5 Recruits Neutrophils in the Absence of C3 during Respiratory Infection with Modified Vaccinia Virus Ankara

Complement Component C5 Recruits Neutrophils in the Absence of C3 during Respiratory Infection with Modified Vaccinia Virus Ankara

Modified Vaccinia virus Ankara but not vaccinia virus induces chemokine expression in cells of the monocyte/macrophage lineage

Broad Protection against Avian Influenza Virus by Using a Modified Vaccinia Ankara Virus Expressing a Mosaic Hemagglutinin Gene

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