The live-attenuated yellow fever vaccine 17D induces broad and potent T cell responses against several viral proteins in Indian rhesus macaques-implications for recombinant vaccine design

Philip A. Mudd, Shari M. Piaskowski, Patricia C Costa Neves, Richard Rudersdorf, Holly L. Kolar, Christopher M. Eernisse, Kim L. Weisgrau, Marlon G Veloso De Santana, Nancy A. Wilson, Myrna C. Bonaldo, Ricardo Galler, Eva G. Rakasz, David Watkins

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The yellow fever vaccine 17D (YF17D) is one of the most effective vaccines. Its wide use and favorable safety profile make it a prime candidate for recombinant vaccines. It is believed that neutralizing antibodies account for a large measure of the protection afforded to YF17D-vaccinated individuals, however cytotoxic T lymphocyte (CTL) responses have been described in the setting of YF17D vaccination. YF17D is an ssRNA flavivirus that is translated as a full-length polyprotein, several domains of which pass into the lumen of the endoplasmic reticulum (ER). The processing and presentation machinery for MHC class I-restricted CTL responses favor cytoplasmic peptides that are transported into the ER by the transporter associated with antigen presentation proteins. In order to inform recombinant vaccine design, we sought to determine if YF17D-induced CTL responses preferentially targeted viral domains that remain within the cytoplasm. We performed whole YF17D proteome mapping of CTL responses in six Indian rhesus macaques vaccinated with YF17D using overlapping YF17D peptides. We found that the ER luminal E protein was the most immunogenic viral protein followed closely by the cytoplasmic NS3 and NS5 proteins. These results suggest that antigen processing and presentation in this model system is not preferentially affected by the subcellular location of the viral proteins that are the source of CTL epitopes. The data also suggest potential immunogenic regions of YF17D that could serve as the focus of recombinant T cell vaccine development.

Original languageEnglish
Pages (from-to)593-600
Number of pages8
JournalImmunogenetics
Volume62
Issue number9
DOIs
StatePublished - Sep 1 2010
Externally publishedYes

Fingerprint

Yellow Fever Vaccine
Attenuated Vaccines
Synthetic Vaccines
Viral Proteins
Macaca mulatta
T-Lymphocytes
Cytotoxic T-Lymphocytes
Antigen Presentation
Endoplasmic Reticulum
Vaccines
Flavivirus
Polyproteins
Peptides
Proteins
T-Lymphocyte Epitopes
Proteome
Neutralizing Antibodies
Cytoplasm
Vaccination

Keywords

  • Cytotoxic T lymphocyte
  • Indian rhesus macaque
  • Vaccine
  • Yellow fever 17D

ASJC Scopus subject areas

  • Immunology
  • Genetics

Cite this

The live-attenuated yellow fever vaccine 17D induces broad and potent T cell responses against several viral proteins in Indian rhesus macaques-implications for recombinant vaccine design. / Mudd, Philip A.; Piaskowski, Shari M.; Neves, Patricia C Costa; Rudersdorf, Richard; Kolar, Holly L.; Eernisse, Christopher M.; Weisgrau, Kim L.; De Santana, Marlon G Veloso; Wilson, Nancy A.; Bonaldo, Myrna C.; Galler, Ricardo; Rakasz, Eva G.; Watkins, David.

In: Immunogenetics, Vol. 62, No. 9, 01.09.2010, p. 593-600.

Research output: Contribution to journalArticle

Mudd, PA, Piaskowski, SM, Neves, PCC, Rudersdorf, R, Kolar, HL, Eernisse, CM, Weisgrau, KL, De Santana, MGV, Wilson, NA, Bonaldo, MC, Galler, R, Rakasz, EG & Watkins, D 2010, 'The live-attenuated yellow fever vaccine 17D induces broad and potent T cell responses against several viral proteins in Indian rhesus macaques-implications for recombinant vaccine design', Immunogenetics, vol. 62, no. 9, pp. 593-600. https://doi.org/10.1007/s00251-010-0461-0
Mudd, Philip A. ; Piaskowski, Shari M. ; Neves, Patricia C Costa ; Rudersdorf, Richard ; Kolar, Holly L. ; Eernisse, Christopher M. ; Weisgrau, Kim L. ; De Santana, Marlon G Veloso ; Wilson, Nancy A. ; Bonaldo, Myrna C. ; Galler, Ricardo ; Rakasz, Eva G. ; Watkins, David. / The live-attenuated yellow fever vaccine 17D induces broad and potent T cell responses against several viral proteins in Indian rhesus macaques-implications for recombinant vaccine design. In: Immunogenetics. 2010 ; Vol. 62, No. 9. pp. 593-600.
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