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

Abstract

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-γ 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.

DNA Vaccines: Progress and Challenges

“…EBV or HIV DNA present in apoptotic bodies can be transferred into APCs and viral epitopes effectively presented by MHC class I molecules (10). Proteins and peptides complexed with heat-shock proteins may be re-presented by APCs (11).…”

Neutralizing activity and cellular immune responses induced in mice after immunization with apoptotic HIV-1/murine leukemia virus infected cells

“…This pseudovirus can infect and replicate in murine cells leading to production of gp120 and gp160 HIV-1 proteins [19] . We were able to show that inoculation of mice with apoptotic HIV-1/ MuLV infected cells induces HIV-1 specific immunity [18] . We used i.p vaccination in the previous study because it allows for induction of immune responses in the spleen of mice.…”

“…or i.n. with either apoptotic HIV-1/MuLV infected or MuLV infected cells as previously reported [18] . In brief, human CEM-1B cells containing the complete murine leukaemia virus A4070 genome were infected with the human immunodeficiency virus type 1 IIIB [23] .…”

“…The day of immunization cells were thawed, washed two times in PBS and exposed to gamma-irradiation (150 Gy) for apoptosis induction, as previously described [18] . Animals were immunized two times with 3 weeks between immunizations.…”

“…In a previous mouse study we raised the question of whether apoptotic HIV-1 infected cells were capable of eliciting HIV-specific immune responses in vivo [18] . To overcome the Hinkula et al 20080917 -4 -cellular tropism of HIV-1, which is a major obstacle in small animal models, we used a pseudotyped virus generated by using the amphotropic MuLV and HIV-1 LAI [19,20] .…”