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Vaccination with Replication Deficient Adenovectors Encoding YF-17D Antigens Induces Long-Lasting Protection from Severe Yellow Fever Virus Infection in Mice.
PLoS Negl Trop Dis. 2016 Feb; 10(2):e0004464.PN

Abstract

The live attenuated yellow fever vaccine (YF-17D) has been successfully used for more than 70 years. It is generally considered a safe vaccine, however, recent reports of serious adverse events following vaccination have raised concerns and led to suggestions that even safer YF vaccines should be developed. Replication deficient adenoviruses (Ad) have been widely evaluated as recombinant vectors, particularly in the context of prophylactic vaccination against viral infections in which induction of CD8+ T-cell mediated immunity is crucial, but potent antibody responses may also be elicited using these vectors. In this study, we present two adenobased vectors targeting non-structural and structural YF antigens and characterize their immunological properties. We report that a single immunization with an Ad-vector encoding the non-structural protein 3 from YF-17D could elicit a strong CD8+ T-cell response, which afforded a high degree of protection from subsequent intracranial challenge of vaccinated mice. However, full protection was only observed using a vector encoding the structural proteins from YF-17D. This vector elicited virus-specific CD8+ T cells as well as neutralizing antibodies, and both components were shown to be important for protection thus mimicking the situation recently uncovered in YF-17D vaccinated mice. Considering that Ad-vectors are very safe, easy to produce and highly immunogenic in humans, our data indicate that a replication deficient adenovector-based YF vaccine may represent a safe and efficient alternative to the classical live attenuated YF vaccine and should be further tested.

Authors+Show Affiliations

Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26886513

Citation

Bassi, Maria R., et al. "Vaccination With Replication Deficient Adenovectors Encoding YF-17D Antigens Induces Long-Lasting Protection From Severe Yellow Fever Virus Infection in Mice." PLoS Neglected Tropical Diseases, vol. 10, no. 2, 2016, pp. e0004464.
Bassi MR, Larsen MA, Kongsgaard M, et al. Vaccination with Replication Deficient Adenovectors Encoding YF-17D Antigens Induces Long-Lasting Protection from Severe Yellow Fever Virus Infection in Mice. PLoS Negl Trop Dis. 2016;10(2):e0004464.
Bassi, M. R., Larsen, M. A., Kongsgaard, M., Rasmussen, M., Buus, S., Stryhn, A., Thomsen, A. R., & Christensen, J. P. (2016). Vaccination with Replication Deficient Adenovectors Encoding YF-17D Antigens Induces Long-Lasting Protection from Severe Yellow Fever Virus Infection in Mice. PLoS Neglected Tropical Diseases, 10(2), e0004464. https://doi.org/10.1371/journal.pntd.0004464
Bassi MR, et al. Vaccination With Replication Deficient Adenovectors Encoding YF-17D Antigens Induces Long-Lasting Protection From Severe Yellow Fever Virus Infection in Mice. PLoS Negl Trop Dis. 2016;10(2):e0004464. PubMed PMID: 26886513.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vaccination with Replication Deficient Adenovectors Encoding YF-17D Antigens Induces Long-Lasting Protection from Severe Yellow Fever Virus Infection in Mice. AU - Bassi,Maria R, AU - Larsen,Mads A B, AU - Kongsgaard,Michael, AU - Rasmussen,Michael, AU - Buus,Søren, AU - Stryhn,Anette, AU - Thomsen,Allan R, AU - Christensen,Jan P, Y1 - 2016/02/17/ PY - 2015/10/04/received PY - 2016/01/26/accepted PY - 2016/2/18/entrez PY - 2016/2/18/pubmed PY - 2016/6/16/medline SP - e0004464 EP - e0004464 JF - PLoS neglected tropical diseases JO - PLoS Negl Trop Dis VL - 10 IS - 2 N2 - The live attenuated yellow fever vaccine (YF-17D) has been successfully used for more than 70 years. It is generally considered a safe vaccine, however, recent reports of serious adverse events following vaccination have raised concerns and led to suggestions that even safer YF vaccines should be developed. Replication deficient adenoviruses (Ad) have been widely evaluated as recombinant vectors, particularly in the context of prophylactic vaccination against viral infections in which induction of CD8+ T-cell mediated immunity is crucial, but potent antibody responses may also be elicited using these vectors. In this study, we present two adenobased vectors targeting non-structural and structural YF antigens and characterize their immunological properties. We report that a single immunization with an Ad-vector encoding the non-structural protein 3 from YF-17D could elicit a strong CD8+ T-cell response, which afforded a high degree of protection from subsequent intracranial challenge of vaccinated mice. However, full protection was only observed using a vector encoding the structural proteins from YF-17D. This vector elicited virus-specific CD8+ T cells as well as neutralizing antibodies, and both components were shown to be important for protection thus mimicking the situation recently uncovered in YF-17D vaccinated mice. Considering that Ad-vectors are very safe, easy to produce and highly immunogenic in humans, our data indicate that a replication deficient adenovector-based YF vaccine may represent a safe and efficient alternative to the classical live attenuated YF vaccine and should be further tested. SN - 1935-2735 UR - https://www.unboundmedicine.com/medline/citation/26886513/Vaccination_with_Replication_Deficient_Adenovectors_Encoding_YF_17D_Antigens_Induces_Long_Lasting_Protection_from_Severe_Yellow_Fever_Virus_Infection_in_Mice_ L2 - https://dx.plos.org/10.1371/journal.pntd.0004464 DB - PRIME DP - Unbound Medicine ER -