Abstract
Human immunodeficiency virus type 1 (HIV-1) canarypox vaccines are safe but poorly immunogenic. CD40 ligand (CD40L), a member of the tumor necrosis factor superfamily (TNFSF), is a pivotal costimulatory molecule for immune responses. To explore whether CD40L can be used as an adjuvant for HIV-1 canarypox vaccine, we constructed recombinant canarypox viruses expressing CD40L. Co-immunization of mice with CD40L expressing canarypox and the canarypox vaccine expressing HIV-1 proteins, vCP1452, augmented HIV-1 specific cytotoxic T lymphocyte (CTL) responses in terms of frequency, polyfunctionality and interleukin (IL)-7 receptor α chain (IL-7Rα, CD127) expression. In addition, CD40L expressed from canarypox virus could significantly augment CD4+ T cell responses against HIV-1 in mice. CD40L expressed from canarypox virus matured human monocyte-derived dendritic cells (MDDCs) in a tumor necrosis factor-α (TNF-α) independent manner, which underwent less apoptosis, and could expand ex vivo Epstein-Barr virus (EBV)-specific CTL responses from healthy human individuals and ex vivo HIV-1-specific CTL responses from HIV-1-infected individuals in the presence or absence of CD4+ T cells. Taken together, our results suggest that CD40L incorporation into poxvirus vectors could be used as a strategy to enhance their immunogenicity.
| Original language | English |
|---|---|
| Pages (from-to) | 4062-4072 |
| Number of pages | 11 |
| Journal | Vaccine |
| Volume | 26 |
| Issue number | 32 |
| DOIs | |
| State | Published - Jul 29 2008 |
| Externally published | Yes |
Fingerprint
Keywords
- AIDS
- Canarypox vector
- Cytotoxic T cell
ASJC Scopus subject areas
- Immunology
- Microbiology
- Virology
- Infectious Diseases
- Public Health, Environmental and Occupational Health
- veterinary(all)
Cite this
CD40L expressed from the canarypox vector, ALVAC, can boost immunogenicity of HIV-1 canarypox vaccine in mice and enhance the in vitro expansion of viral specific CD8+ T cell memory responses from HIV-1-infected and HIV-1-uninfected individuals. / Liu, Jun; Yu, Qigui; Stone, Geoffrey; Yue, Feng Yun; Ngai, Nicholas; Jones, R. Brad; Kornbluth, Richard S.; Ostrowski, Mario A.
In: Vaccine, Vol. 26, No. 32, 29.07.2008, p. 4062-4072.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CD40L expressed from the canarypox vector, ALVAC, can boost immunogenicity of HIV-1 canarypox vaccine in mice and enhance the in vitro expansion of viral specific CD8+ T cell memory responses from HIV-1-infected and HIV-1-uninfected individuals
AU - Liu, Jun
AU - Yu, Qigui
AU - Stone, Geoffrey
AU - Yue, Feng Yun
AU - Ngai, Nicholas
AU - Jones, R. Brad
AU - Kornbluth, Richard S.
AU - Ostrowski, Mario A.
PY - 2008/7/29
Y1 - 2008/7/29
N2 - Human immunodeficiency virus type 1 (HIV-1) canarypox vaccines are safe but poorly immunogenic. CD40 ligand (CD40L), a member of the tumor necrosis factor superfamily (TNFSF), is a pivotal costimulatory molecule for immune responses. To explore whether CD40L can be used as an adjuvant for HIV-1 canarypox vaccine, we constructed recombinant canarypox viruses expressing CD40L. Co-immunization of mice with CD40L expressing canarypox and the canarypox vaccine expressing HIV-1 proteins, vCP1452, augmented HIV-1 specific cytotoxic T lymphocyte (CTL) responses in terms of frequency, polyfunctionality and interleukin (IL)-7 receptor α chain (IL-7Rα, CD127) expression. In addition, CD40L expressed from canarypox virus could significantly augment CD4+ T cell responses against HIV-1 in mice. CD40L expressed from canarypox virus matured human monocyte-derived dendritic cells (MDDCs) in a tumor necrosis factor-α (TNF-α) independent manner, which underwent less apoptosis, and could expand ex vivo Epstein-Barr virus (EBV)-specific CTL responses from healthy human individuals and ex vivo HIV-1-specific CTL responses from HIV-1-infected individuals in the presence or absence of CD4+ T cells. Taken together, our results suggest that CD40L incorporation into poxvirus vectors could be used as a strategy to enhance their immunogenicity.
AB - Human immunodeficiency virus type 1 (HIV-1) canarypox vaccines are safe but poorly immunogenic. CD40 ligand (CD40L), a member of the tumor necrosis factor superfamily (TNFSF), is a pivotal costimulatory molecule for immune responses. To explore whether CD40L can be used as an adjuvant for HIV-1 canarypox vaccine, we constructed recombinant canarypox viruses expressing CD40L. Co-immunization of mice with CD40L expressing canarypox and the canarypox vaccine expressing HIV-1 proteins, vCP1452, augmented HIV-1 specific cytotoxic T lymphocyte (CTL) responses in terms of frequency, polyfunctionality and interleukin (IL)-7 receptor α chain (IL-7Rα, CD127) expression. In addition, CD40L expressed from canarypox virus could significantly augment CD4+ T cell responses against HIV-1 in mice. CD40L expressed from canarypox virus matured human monocyte-derived dendritic cells (MDDCs) in a tumor necrosis factor-α (TNF-α) independent manner, which underwent less apoptosis, and could expand ex vivo Epstein-Barr virus (EBV)-specific CTL responses from healthy human individuals and ex vivo HIV-1-specific CTL responses from HIV-1-infected individuals in the presence or absence of CD4+ T cells. Taken together, our results suggest that CD40L incorporation into poxvirus vectors could be used as a strategy to enhance their immunogenicity.
KW - AIDS
KW - Canarypox vector
KW - Cytotoxic T cell
UR - http://www.scopus.com/inward/record.url?scp=47149112188&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=47149112188&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2008.05.018
DO - 10.1016/j.vaccine.2008.05.018
M3 - Article
C2 - 18562053
AN - SCOPUS:47149112188
VL - 26
SP - 4062
EP - 4072
JO - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 32
ER -