Next Article in Journal
Atomic Resolution Structures of Human Bufaviruses Determined by Cryo-Electron Microscopy
Next Article in Special Issue
Vaccinia Virus in Blood Samples of Humans, Domestic and Wild Mammals in Brazil
Previous Article in Journal
Blood Coagulation Factor X Exerts Differential Effects on Adenovirus Entry into Human Lymphocytes
Previous Article in Special Issue
A Model to Detect Autochthonous Group 1 and 2 Brazilian Vaccinia virus Coinfections: Development of a qPCR Tool for Diagnosis and Pathogenesis Studies
Article Menu
Issue 1 (January) cover image

Export Article

Open AccessArticle
Viruses 2018, 10(1), 21; doi:10.3390/v10010021

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

1
Lehrstuhl für Virologie, Institut für Infektionsmedizin und Zoonosen, Ludwig-Maximilians-Universität München, 80539 Munich, Germany
2
Deutsches Zentrum für Infektionsforschung (DZIF), 80539 Munich, Germany
3
Division of Virology, Paul-Ehrlich-Institut, 63225 Langen, Germany
*
Author to whom correspondence should be addressed.
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?)
View Full-Text   |   Download PDF [1221 KB, uploaded 4 January 2018]   |  

Abstract

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
Figures

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).

Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top