Unknown

Dataset Information

0

Pre-clinical efficacy and safety of experimental vaccines based on non-replicating vaccinia vectors against yellow fever.


ABSTRACT: BACKGROUND: Currently existing yellow fever (YF) vaccines are based on the live attenuated yellow fever virus 17D strain (YFV-17D). Although, a good safety profile was historically attributed to the 17D vaccine, serious adverse events have been reported, making the development of a safer, more modern vaccine desirable. METHODOLOGY/PRINCIPAL FINDINGS: A gene encoding the precursor of the membrane and envelope (prME) protein of the YFV-17D strain was inserted into the non-replicating modified vaccinia virus Ankara and into the D4R-defective vaccinia virus. Candidate vaccines based on the recombinant vaccinia viruses were assessed for immunogenicity and protection in a mouse model and compared to the commercial YFV-17D vaccine. The recombinant live vaccines induced γ-interferon-secreting CD4- and functionally active CD8-T cells, and conferred full protection against lethal challenge already after a single low immunization dose of 10(5) TCID(50). Surprisingly, pre-existing immunity against wild-type vaccinia virus did not negatively influence protection. Unlike the classical 17D vaccine, the vaccinia virus-based vaccines did not cause mortality following intracerebral administration in mice, demonstrating better safety profiles. CONCLUSIONS/SIGNIFICANCE: The non-replicating recombinant YF candidate live vaccines induced a broad immune response after single dose administration, were effective even in the presence of a pre-existing immunity against vaccinia virus and demonstrated an excellent safety profile in mice.

SUBMITTER: Schafer B 

PROVIDER: S-EPMC3170363 | BioStudies | 2011-01-01

SECONDARY ACCESSION(S): NC_002031

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC6082969 | BioStudies
2015-01-01 | S-EPMC4811652 | BioStudies
2020-01-01 | S-EPMC7067203 | BioStudies
2020-01-01 | S-EPMC7157777 | BioStudies
2019-01-01 | S-EPMC6805994 | BioStudies
2016-01-01 | S-EPMC4757529 | BioStudies
1000-01-01 | S-EPMC6292895 | BioStudies
2009-01-01 | S-EPMC2749449 | BioStudies
2020-01-01 | S-EPMC7221214 | BioStudies
2019-01-01 | S-EPMC6709925 | BioStudies