Abstract
The Modified Vaccinia virus Ankara (MVA) is a highly attenuated vaccinia virus serving as a promising vector vaccine platform to develop vaccines against infectious diseases. In contrast to the well-established replication deficiency and safety of MVA in mammals, much less is known about MVA infection in avian hosts. Here, we used a recombinant MVA expressing fluorescent reporter proteins under transcriptional control of specific viral early and late promoters to study in vivo tropism, distribution, and pathogenesis of MVA infections in embryonated chicken eggs. The chorioallantoic membrane (CAM) of embryonated chicken eggs was inoculated with recombinant MVA, MVA or phosphate-buffered saline. The infection was analyzed by fluorescence microscopy, histology, immunohistochemistry, and virus titration of embryonic tissues. After infection of the CAM, MVA spread to internal and external embryonic tissues with the liver as a major target organ. Macrophages and hematopoietic cells were identified as primary target cells of MVA infection and may be involved in virus spread. Increasing doses of MVA did not result in increased lesion severity or embryonic death. Despite MVA generalization to embryonic tissues, the CAM seems to be the major site of MVA replication. The absence of considerable organ lesions and MVA-associated mortality highlights an excellent safety profile of MVA in chicken hosts.
Highlights
Modified Vaccinia virus Ankara (MVA) was originally generated by Anton Mayr and EberhardMunz in the 1960s [1]
The new virus differed from the parental Chorioallantoic VACV Ankara (CVA) in several biomarkers of infection including the tropism in cell culture, the behavior in embryonated chicken eggs and the loss of virulence for mice, and rabbits [2]
In MVA-green fluorescent protein (GFP)-mCherry inoculated chorioallantoic membrane (CAM), we found these pock lesions to be consistently associated with the detection of green and strong red fluorescence (Figure 1b,c)
Summary
Modified Vaccinia virus Ankara (MVA) was originally generated by Anton Mayr and EberhardMunz in the 1960s [1]. Modified Vaccinia virus Ankara (MVA) was originally generated by Anton Mayr and Eberhard. The starting point was a study encompassing serial infection experiments in cultures of primary chicken embryo fibroblasts (CEF) with a standard vaccinia virus (VACV) strain, the Chorioallantoic VACV Ankara (CVA), being used for vaccination against smallpox in Turkey and Germany. After over 516 passages in CEF, a highly attenuated laboratory virus had emerged which was renamed MVA. The new virus differed from the parental CVA in several biomarkers of infection including the tropism in cell culture, the behavior in embryonated chicken eggs and the loss of virulence for mice, and rabbits [2]. The attenuated phenotype of MVA infection is associated with substantial changes in the viral genome involving large genomic deletions and fragmentation, truncation and deletion of multiple open reading frames typically found in VACV genomes [3,4].
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