Rapid memory CD8+ T-lymphocyte induction through priming with recombinant Mycobacterium smegmatis

Avi Hai Hovav, Mark J. Cayabyab, Michael W. Panas, Sampa Santra, John Greenland, Ralf Geiben, Barton F. Haynes, William R. Jacobs, Norman L. Letvin

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The most promising vaccine strategies for the induction of cytotoxic-T-lymphocyte responses have been heterologons prime/boost regimens employing a plasmid DNA prime and a live recombinant-vector boost. The priming immunogen in these regimens must elicit antigen-specific memory CD8+ T lymphocytes that will expand following the boosting immunization. Because plasmid DNA immunogens are expensive and their immunogenicity has proven disappointing in human clinical trials, we have been exploring novel priming immunogens that might be used in heterologous immunization regimens. Here we show that priming with a prototype recombinant Mycobacterium smegmatis strain expressing human immunodeficiency virus type 1 (HIV-1) gp120-elicited CD4 + T lymphocytes with a functional profile of helper cells as well as a CD8+ T-lymphocyte population. These CD8+ T lymphocytes rapidly differentiated to memory cells, defined on the basis of their cytokine profile and expression of CD62L and CD27. Moreover, these recombinant- mycobacterium-induced T lymphocytes rapidly expanded following boosting with a recombinant adenovirus expressing HIV-1 Env to gp120-specific CD8+ T lymphocytes. This work demonstrates a remarkable skewing of recombinant- mycobacterium-induced T lymphocytes to durable antigen-specific memory CD8 + T cells and suggests that such immunogens might be used as priming vectors in prime/boost vaccination regimens for the induction of cellular immune responses.

Original languageEnglish (US)
Pages (from-to)74-83
Number of pages10
JournalJournal of virology
Volume81
Issue number1
DOIs
StatePublished - Jan 1 2007

Fingerprint

Mycobacterium smegmatis
T-lymphocytes
T-Lymphocytes
antigens
Mycobacterium
Human immunodeficiency virus 1
HIV-1
Immunization
plasmids
immunization
Plasmids
Antigens
cytotoxic T-lymphocytes
DNA
Cytotoxic T-Lymphocytes
Adenoviridae
Helper-Inducer T-Lymphocytes
prototypes
Cellular Immunity
cell-mediated immunity

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Hovav, A. H., Cayabyab, M. J., Panas, M. W., Santra, S., Greenland, J., Geiben, R., ... Letvin, N. L. (2007). Rapid memory CD8+ T-lymphocyte induction through priming with recombinant Mycobacterium smegmatis. Journal of virology, 81(1), 74-83. https://doi.org/10.1128/JVI.01269-06

Rapid memory CD8+ T-lymphocyte induction through priming with recombinant Mycobacterium smegmatis. / Hovav, Avi Hai; Cayabyab, Mark J.; Panas, Michael W.; Santra, Sampa; Greenland, John; Geiben, Ralf; Haynes, Barton F.; Jacobs, William R.; Letvin, Norman L.

In: Journal of virology, Vol. 81, No. 1, 01.01.2007, p. 74-83.

Research output: Contribution to journalArticle

Hovav, AH, Cayabyab, MJ, Panas, MW, Santra, S, Greenland, J, Geiben, R, Haynes, BF, Jacobs, WR & Letvin, NL 2007, 'Rapid memory CD8+ T-lymphocyte induction through priming with recombinant Mycobacterium smegmatis', Journal of virology, vol. 81, no. 1, pp. 74-83. https://doi.org/10.1128/JVI.01269-06
Hovav, Avi Hai ; Cayabyab, Mark J. ; Panas, Michael W. ; Santra, Sampa ; Greenland, John ; Geiben, Ralf ; Haynes, Barton F. ; Jacobs, William R. ; Letvin, Norman L. / Rapid memory CD8+ T-lymphocyte induction through priming with recombinant Mycobacterium smegmatis. In: Journal of virology. 2007 ; Vol. 81, No. 1. pp. 74-83.
@article{14162d0a77ee41e38e04e86db5063e56,
title = "Rapid memory CD8+ T-lymphocyte induction through priming with recombinant Mycobacterium smegmatis",
abstract = "The most promising vaccine strategies for the induction of cytotoxic-T-lymphocyte responses have been heterologons prime/boost regimens employing a plasmid DNA prime and a live recombinant-vector boost. The priming immunogen in these regimens must elicit antigen-specific memory CD8+ T lymphocytes that will expand following the boosting immunization. Because plasmid DNA immunogens are expensive and their immunogenicity has proven disappointing in human clinical trials, we have been exploring novel priming immunogens that might be used in heterologous immunization regimens. Here we show that priming with a prototype recombinant Mycobacterium smegmatis strain expressing human immunodeficiency virus type 1 (HIV-1) gp120-elicited CD4 + T lymphocytes with a functional profile of helper cells as well as a CD8+ T-lymphocyte population. These CD8+ T lymphocytes rapidly differentiated to memory cells, defined on the basis of their cytokine profile and expression of CD62L and CD27. Moreover, these recombinant- mycobacterium-induced T lymphocytes rapidly expanded following boosting with a recombinant adenovirus expressing HIV-1 Env to gp120-specific CD8+ T lymphocytes. This work demonstrates a remarkable skewing of recombinant- mycobacterium-induced T lymphocytes to durable antigen-specific memory CD8 + T cells and suggests that such immunogens might be used as priming vectors in prime/boost vaccination regimens for the induction of cellular immune responses.",
author = "Hovav, {Avi Hai} and Cayabyab, {Mark J.} and Panas, {Michael W.} and Sampa Santra and John Greenland and Ralf Geiben and Haynes, {Barton F.} and Jacobs, {William R.} and Letvin, {Norman L.}",
year = "2007",
month = "1",
day = "1",
doi = "10.1128/JVI.01269-06",
language = "English (US)",
volume = "81",
pages = "74--83",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "1",

}

TY - JOUR

T1 - Rapid memory CD8+ T-lymphocyte induction through priming with recombinant Mycobacterium smegmatis

AU - Hovav, Avi Hai

AU - Cayabyab, Mark J.

AU - Panas, Michael W.

AU - Santra, Sampa

AU - Greenland, John

AU - Geiben, Ralf

AU - Haynes, Barton F.

AU - Jacobs, William R.

AU - Letvin, Norman L.

PY - 2007/1/1

Y1 - 2007/1/1

N2 - The most promising vaccine strategies for the induction of cytotoxic-T-lymphocyte responses have been heterologons prime/boost regimens employing a plasmid DNA prime and a live recombinant-vector boost. The priming immunogen in these regimens must elicit antigen-specific memory CD8+ T lymphocytes that will expand following the boosting immunization. Because plasmid DNA immunogens are expensive and their immunogenicity has proven disappointing in human clinical trials, we have been exploring novel priming immunogens that might be used in heterologous immunization regimens. Here we show that priming with a prototype recombinant Mycobacterium smegmatis strain expressing human immunodeficiency virus type 1 (HIV-1) gp120-elicited CD4 + T lymphocytes with a functional profile of helper cells as well as a CD8+ T-lymphocyte population. These CD8+ T lymphocytes rapidly differentiated to memory cells, defined on the basis of their cytokine profile and expression of CD62L and CD27. Moreover, these recombinant- mycobacterium-induced T lymphocytes rapidly expanded following boosting with a recombinant adenovirus expressing HIV-1 Env to gp120-specific CD8+ T lymphocytes. This work demonstrates a remarkable skewing of recombinant- mycobacterium-induced T lymphocytes to durable antigen-specific memory CD8 + T cells and suggests that such immunogens might be used as priming vectors in prime/boost vaccination regimens for the induction of cellular immune responses.

AB - The most promising vaccine strategies for the induction of cytotoxic-T-lymphocyte responses have been heterologons prime/boost regimens employing a plasmid DNA prime and a live recombinant-vector boost. The priming immunogen in these regimens must elicit antigen-specific memory CD8+ T lymphocytes that will expand following the boosting immunization. Because plasmid DNA immunogens are expensive and their immunogenicity has proven disappointing in human clinical trials, we have been exploring novel priming immunogens that might be used in heterologous immunization regimens. Here we show that priming with a prototype recombinant Mycobacterium smegmatis strain expressing human immunodeficiency virus type 1 (HIV-1) gp120-elicited CD4 + T lymphocytes with a functional profile of helper cells as well as a CD8+ T-lymphocyte population. These CD8+ T lymphocytes rapidly differentiated to memory cells, defined on the basis of their cytokine profile and expression of CD62L and CD27. Moreover, these recombinant- mycobacterium-induced T lymphocytes rapidly expanded following boosting with a recombinant adenovirus expressing HIV-1 Env to gp120-specific CD8+ T lymphocytes. This work demonstrates a remarkable skewing of recombinant- mycobacterium-induced T lymphocytes to durable antigen-specific memory CD8 + T cells and suggests that such immunogens might be used as priming vectors in prime/boost vaccination regimens for the induction of cellular immune responses.

UR - http://www.scopus.com/inward/record.url?scp=33845794802&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845794802&partnerID=8YFLogxK

U2 - 10.1128/JVI.01269-06

DO - 10.1128/JVI.01269-06

M3 - Article

C2 - 17050608

AN - SCOPUS:33845794802

VL - 81

SP - 74

EP - 83

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 1

ER -