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Pre-clinical efficacy and safety of experimental vaccines based on non-replicating vaccinia vectors against yellow fever.
PLoS One. 2011; 6(9):e24505.Plos

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.

Authors+Show Affiliations

Department of Virology, Baxter Bioscience, Biomedical Research Center, Orth/Donau, Austria.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21931732

Citation

Schäfer, Birgit, et al. "Pre-clinical Efficacy and Safety of Experimental Vaccines Based On Non-replicating Vaccinia Vectors Against Yellow Fever." PloS One, vol. 6, no. 9, 2011, pp. e24505.
Schäfer B, Holzer GW, Joachimsthaler A, et al. Pre-clinical efficacy and safety of experimental vaccines based on non-replicating vaccinia vectors against yellow fever. PLoS One. 2011;6(9):e24505.
Schäfer, B., Holzer, G. W., Joachimsthaler, A., Coulibaly, S., Schwendinger, M., Crowe, B. A., Kreil, T. R., Barrett, P. N., & Falkner, F. G. (2011). Pre-clinical efficacy and safety of experimental vaccines based on non-replicating vaccinia vectors against yellow fever. PloS One, 6(9), e24505. https://doi.org/10.1371/journal.pone.0024505
Schäfer B, et al. Pre-clinical Efficacy and Safety of Experimental Vaccines Based On Non-replicating Vaccinia Vectors Against Yellow Fever. PLoS One. 2011;6(9):e24505. PubMed PMID: 21931732.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pre-clinical efficacy and safety of experimental vaccines based on non-replicating vaccinia vectors against yellow fever. AU - Schäfer,Birgit, AU - Holzer,Georg W, AU - Joachimsthaler,Alexandra, AU - Coulibaly,Sogue, AU - Schwendinger,Michael, AU - Crowe,Brian A, AU - Kreil,Thomas R, AU - Barrett,P Noel, AU - Falkner,Falko G, Y1 - 2011/09/09/ PY - 2010/11/09/received PY - 2011/08/12/accepted PY - 2011/9/21/entrez PY - 2011/9/21/pubmed PY - 2012/6/9/medline SP - e24505 EP - e24505 JF - PloS one JO - PLoS One VL - 6 IS - 9 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/21931732/Pre_clinical_efficacy_and_safety_of_experimental_vaccines_based_on_non_replicating_vaccinia_vectors_against_yellow_fever_ L2 - https://dx.plos.org/10.1371/journal.pone.0024505 DB - PRIME DP - Unbound Medicine ER -