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The Journal of Immunology, 2002, 169: 5771-5779.
Copyright © 2002 by The American Association of Immunologists

Induction of HIV-1-Specific Immunity After Vaccination with Apoptotic HIV-1/Murine Leukemia Virus-Infected Cells1

Anna-Lena Spetz2,*, Anna Smed Sörensen*, Lilian Walther-Jallow*, Britta Wahren{dagger},{ddagger}, Jan Andersson*, Lars Holmgren§ and Jorma Hinkula{dagger},{ddagger}

* Department of Medicine, Center for Infectious Medicine, Huddinge University Hospital, and {dagger} Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden; {ddagger} Swedish Institute for Infectious Disease Control, Stockholm, Sweden; § Cancer Center, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden; and Department of Health and Society, Malmö University, Malmö, Sweden

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.




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