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E3L and F1L Gene Functions Modulate the Protective Capacity of Modified Vaccinia Virus Ankara Immunization in Murine Model of Human Smallpox

Lehrstuhl für Virologie, Institut für Infektionsmedizin und Zoonosen, Ludwig-Maximilians-Universität München, 80539 Munich, Germany
Deutsches Zentrum für Infektionsforschung (DZIF), 80539 Munich, Germany
Division of Virology, Paul-Ehrlich-Institut, 63225 Langen, Germany
Author to whom correspondence should be addressed.
Viruses 2018, 10(1), 21;
Received: 22 November 2017 / Revised: 17 December 2017 / Accepted: 28 December 2017 / Published: 4 January 2018
(This article belongs to the Special Issue Smallpox and Emerging Zoonotic Orthopoxviruses: What Is Coming Next?)
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The highly attenuated Modified Vaccinia virus Ankara (MVA) lacks most of the known vaccinia virus (VACV) virulence and immune evasion genes. Today MVA can serve as a safety-tested next-generation smallpox vaccine. Yet, we still need to learn about regulatory gene functions preserved in the MVA genome, such as the apoptosis inhibitor genes F1L and E3L. Here, we tested MVA vaccine preparations on the basis of the deletion mutant viruses MVA-ΔF1L and MVA-ΔE3L for efficacy against ectromelia virus (ECTV) challenge infections in mice. In non-permissive human tissue culture the MVA deletion mutant viruses produced reduced levels of the VACV envelope antigen B5. Upon mousepox challenge at three weeks after vaccination, MVA-ΔF1L and MVA-ΔE3L exhibited reduced protective capacity in comparison to wildtype MVA. Surprisingly, however, all vaccines proved equally protective against a lethal ECTV infection at two days after vaccination. Accordingly, the deletion mutant MVA vaccines induced high levels of virus-specific CD8+ T cells previously shown to be essential for rapidly protective MVA vaccination. These results suggest that inactivation of the anti-apoptotic genes F1L or E3L modulates the protective capacity of MVA vaccination most likely through the induction of distinct orthopoxvirus specific immunity in the absence of these viral regulatory proteins. View Full-Text
Keywords: smallpox vaccination; MVA; immunogenic cell death; emergency vaccination smallpox vaccination; MVA; immunogenic cell death; emergency vaccination

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Volz, A.; Jany, S.; Freudenstein, A.; Lantermann, M.; Ludwig, H.; Sutter, G. E3L and F1L Gene Functions Modulate the Protective Capacity of Modified Vaccinia Virus Ankara Immunization in Murine Model of Human Smallpox. Viruses 2018, 10, 21.

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