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.
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 alpha chain (IL-7Ralpha, 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-alpha (TNF-alpha) 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.
Clinical Sciences Division, University of Toronto, Toronto, Ontario, Canada.
Jun
J
Liu
Qigui
Q
Yu
Geoffrey W
GW
Stone
Feng Yun
FY
Yue
Nicholas
N
Ngai
R Brad
RB
Jones
Richard S
RS
Kornbluth
Mario A
MA
Ostrowski
D016915:AIDS Vaccines / Q000737:chemistry / Q000276:immunology; D000276:Adjuvants, Immunologic; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D023201:CD40 Ligand / Q000378:metabolism* / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D028121:Canarypox virus / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects; D005260:Female; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D014765:Viral Vaccines / Q000378:metabolism*
D016915:AIDS Vaccines; C078788:ALVAC vaccine; D000276:Adjuvants, Immunologic; D014765:Viral Vaccines; D023201:CD40 Ligand