Modified Vaccinia Virus Ankara Triggers Chemotaxis of Monocytes and Early Respiratory Immigration of Leukocytes by Induction of CCL2 Expression

Lehmann, Michael H.; Kastenmüller, Wolfgang; Kandemir, Judith D.; Brandt, Florian; Suezer, Yasemin; Sutter, Gerd

doi:10.1128/jvi.01884-08

Cited by 71 publications

(87 citation statements)

References 51 publications

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“…MVA induces NFκB activation (23) and robust neutrophil recruitment after intranasal (36) or intradermal infection (37). We demonstrate that, after i.p.…”

Section: Discussionmentioning

confidence: 94%

NFκB activation by modified vaccinia virus as a novel strategy to enhance neutrophil migration and HIV-specific T-cell responses

Pilato¹,

Mejías-Pérez²,

Zonca

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Neutrophils are antigen-transporting cells that generate vaccinia virus (VACV)-specific T-cell responses, yet how VACV modulates neutrophil recruitment and its significance in the immune response are unknown. We generated an attenuated VACV strain that expresses HIV-1 clade C antigens but lacks three specific viral genes (A52R, K7R, and B15R). We found that these genes act together to inhibit the NFκB signaling pathway. Triple ablation in modified virus restored NFκB function in macrophages. After virus infection of mice, NFκB pathway activation led to expression of several cytokines/chemokines that increased the migration of neutrophil populations (Nα and Nβ) to the infection site. Nβ cells displayed features of antigen-presenting cells and activated virus-specific CD8 T cells. Enhanced neutrophil trafficking to the infection site correlated with an increased T-cell response to HIV vector-delivered antigens. These results identify a mechanism for poxvirus-induced immune response and alternatives for vaccine vector design.

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“…MVA induces NFκB activation (23) and robust neutrophil recruitment after intranasal (36) or intradermal infection (37). We demonstrate that, after i.p.…”

Section: Discussionmentioning

confidence: 94%

NFκB activation by modified vaccinia virus as a novel strategy to enhance neutrophil migration and HIV-specific T-cell responses

Pilato¹,

Mejías-Pérez²,

Zonca

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…It has been demonstrated that recombinant MVA driving the expression of foreign genes can be used as a viral vector. high-level clinical safety, the availability of technologies for large-scale manufacturing, the ability to deliver substantial amounts of recombinant antigen and a particular immunostimulatory capacity due to adjuvant host responses such as type I interferon and chemokine synthesis (Lehmann et al, 2009;Waibler et al, 2007). Thus, recombinant MVA is an interesting candidate vector to serve as a high-yield production platform for pandemic influenza vaccines (Drexler et al, 2004;Rimmelzwaan & Sutter, 2009).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a modified vaccinia virus Ankara (MVA)-based candidate pandemic influenza A/H1N1 vaccine in the ferret model

Kreijtz¹,

Süzer

Bodewes³

et al. 2010

Journal of General Virology

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“…MVA has lost many of the host modulatory factors that are encoded in wild-type orthopoxviruses (11), including the virally encoded complement control protein that is a known virulence factor (12,13). Previously, we have shown that MVA, but not other VACV strains, induces robust innate immune responses including the early recruitment of leukocytes into the lung (14). During the early stages of MVA infection, neutrophils make up a large portion of infiltrating leukocytes, which are recruited by a mechanism involving CCR1 (15).…”

mentioning

confidence: 99%

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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Modified Vaccinia Virus Ankara Triggers Chemotaxis of Monocytes and Early Respiratory Immigration of Leukocytes by Induction of CCL2 Expression

Cited by 71 publications

References 51 publications

NFκB activation by modified vaccinia virus as a novel strategy to enhance neutrophil migration and HIV-specific T-cell responses

NFκB activation by modified vaccinia virus as a novel strategy to enhance neutrophil migration and HIV-specific T-cell responses

Evaluation of a modified vaccinia virus Ankara (MVA)-based candidate pandemic influenza A/H1N1 vaccine in the ferret model

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

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