Exploiting cross-priming to generate protective CD8 T-cell immunity rapidly

Nhat Long L Pham, Lecia L. Pewe, Courtney J. Fleenor, Ryan A. Langlois, Kevin L. Legge, Vladimir P. Badovinac, John T. Harty

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

The number of memory CD8 T cells generated by infection or vaccination correlates strongly with the degree of protection observed in infection and tumor models. Therefore, rapid induction of protective numbers of effector and memory CD8 T cells may be crucial in the case of malignancy, pandemic infection, or bioterrorism. Many studies have shown that amplifying T-cell numbers by prime-boost vaccination is most effective with a substantial time interval between immunizations. In contrast, immunization with peptide-coated mature dendritic cells (DCs) results in a CD8 T-cell response exhibiting accelerated acquisition of memory characteristics, including the ability to respond to booster immunization within days of initial priming. However, personalized DC immunization is too costly, labor intensive, and time-consuming for large-scale vaccination. Here, we demonstrate that in vivo cross-priming with cell-associated antigens or antigen-coated, biodegradable microspheres in the absence of adjuvant quickly generates CD8 T cells that display the phenotype and function of long-term memory populations. Importantly, cross-primed CD8 T cells can respond to booster immunization within days of the initial immunization to generate rapidly large numbers of effector and memory T cells that can protect against bacterial, viral, and parasitic infections, including lethal influenza and malaria-causing Plasmodium infection. Thus, accelerated CD8 T-cell memory after in vivo cross-priming in the absence of adjuvant is generalizable and can be exploited to generate protective immunity rapidly.

Original languageEnglish (US)
Pages (from-to)12198-12203
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number27
DOIs
StatePublished - Jul 6 2010

Fingerprint

Cross-Priming
Immunity
T-Lymphocytes
Immunization
Secondary Immunization
Vaccination
Dendritic Cells
Malaria
Infection
Bioterrorism
Antigens
Parasitic Diseases
Aptitude
Long-Term Memory
Pandemics
Virus Diseases
Microspheres
Bacterial Infections
Human Influenza
Neoplasms

Keywords

  • Protective immunity
  • Vaccination

ASJC Scopus subject areas

  • General

Cite this

Pham, N. L. L., Pewe, L. L., Fleenor, C. J., Langlois, R. A., Legge, K. L., Badovinac, V. P., & Harty, J. T. (2010). Exploiting cross-priming to generate protective CD8 T-cell immunity rapidly. Proceedings of the National Academy of Sciences of the United States of America, 107(27), 12198-12203. https://doi.org/10.1073/pnas.1004661107

Exploiting cross-priming to generate protective CD8 T-cell immunity rapidly. / Pham, Nhat Long L; Pewe, Lecia L.; Fleenor, Courtney J.; Langlois, Ryan A.; Legge, Kevin L.; Badovinac, Vladimir P.; Harty, John T.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 27, 06.07.2010, p. 12198-12203.

Research output: Contribution to journalArticle

Pham, NLL, Pewe, LL, Fleenor, CJ, Langlois, RA, Legge, KL, Badovinac, VP & Harty, JT 2010, 'Exploiting cross-priming to generate protective CD8 T-cell immunity rapidly', Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 27, pp. 12198-12203. https://doi.org/10.1073/pnas.1004661107
Pham, Nhat Long L ; Pewe, Lecia L. ; Fleenor, Courtney J. ; Langlois, Ryan A. ; Legge, Kevin L. ; Badovinac, Vladimir P. ; Harty, John T. / Exploiting cross-priming to generate protective CD8 T-cell immunity rapidly. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 27. pp. 12198-12203.
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