Induction of HIV-1-specific immunity after vaccination with apoptotic HIV-1/murine leukemia virus-infected cells.
Ag-presenting dendritic cells present viral Ags to T cells after uptake of apoptotic bodies derived from virus-infected cells in vitro. However, it is unclear whether apoptotic virus-infected cells are capable of generating immunity in vivo. In this study, we show that inoculation of mice with apoptotic HIV-1/murine leukemia virus (MuLV)-infected cells induces HIV-1-specific immunity. Immunization with apoptotic HIV-1/MuLV-infected syngeneic splenocytes resulted in strong Nef-specific CD8(+) T cell proliferation and p24-induced CD4(+) and CD8(+) T cell proliferation as well as IFN-gamma production. In addition, systemic IgG and IgA as well as mucosa-associated IgA responses were generated. Moreover, mice vaccinated with apoptotic HIV-1/MuLV cells were protected against challenge with live HIV-1/MuLV-infected cells, whereas mice vaccinated with apoptotic noninfected or MuLV-infected splenocytes remained susceptible to HIV-1/MuLV. These data show that i.p. immunization with apoptotic HIV-1-infected cells induces high levels of HIV-1-specific systemic immunity, primes for mucosal immunity, and induces protection against challenge with live HIV-1-infected cells in mice. These findings may have implications for the development of therapeutic and prophylactic HIV-1 vaccines.
Spetz
Anna-Lena
AL
Department of Medicine, Center for Infectious Medicine, Huddinge University Hospital, F82 Karolinska Institutet, S-141 86 Stockholm, Sweden. anna-lena.spetz@medhs.ki.se
Sörensen
Anna Smed
AS
Walther-Jallow
Lilian
L
Wahren
Britta
B
Andersson
Jan
J
Holmgren
Lars
L
Hinkula
Jorma
J
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015483:HIV Antibodies / Q000096:biosynthesis / Q000097:blood; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007274:Injections, Intraperitoneal; D009052:Leukemia Virus, Murine / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D013154:Spleen / Q000166:cytology* / Q000637:transplantation* / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015483:HIV Antibodies