Detection of simian immunodeficiency virus (SIV)-specific CD8+ T cells in macaques protected from SIV challenge by prior SIV subunit vaccination.

AUTOR(ES)

Kent, S J

RESUMO

Vaccines for lentiviruses would ideally induce in the host complete resistance to infection of host cells. However, such sterilizing immunity may be neither readily achievable nor absolutely necessary to provide protection from exposure to the immunodeficiency viruses. To examine the nature of protective immunity to simian immunodeficiency virus (SIV), we studied three macaques that had been immunized with a recombinant vaccinia virus-based SIV subunit vaccine regimen and exhibited protection from a challenge with cell-free SIV (MNE) as determined by viral cultures, serology, and PCR for viral genomes. Peripheral blood mononuclear cells were obtained from the protected macaques and analyzed for CD8+ cytotoxic T-lymphocyte (CTL) responses to SIV proteins. CTL reactive to SIV proteins not included in the subunit vaccine, and thus to which these animals had not been exposed prior to challenge, were detected postchallenge in the vaccine-protected animals and persisted for up to 1 year. These CTL, as reflected by studies of cytolytic lines and derived T-cell clones, were CD8+, did not recognize allogeneic targets, and recognized the SIV proteins in the context of class I major histocompatibility complex molecules. The frequency of precursor CD8+ CTL reactive to SIV proteins was determined by limiting-dilution analysis and demonstrated that the responses elicited following challenge of protected animals to SIV proteins not present in the vaccine were quantitatively similar to those of animals persistently infected with SIV. The presence of these CD8+ CTL responses to SIV proteins present only in the challenge virus suggests that infection of some host cells occurred postchallenge. These results suggest that the development of a low level of SIV infection following exposure of vaccinated hosts to SIV does not preclude protection from lethal SIV disease by vaccine-induced immunity.

Documentos Relacionados

• Inhibition of Simian Immunodeficiency Virus (SIV) Replication by CD8+ T Lymphocytes from Macaques Immunized with Live Attenuated SIV
• Occult Systemic Infection and Persistent Simian Immunodeficiency Virus (SIV)-Specific CD4+-T-Cell Proliferative Responses in Rhesus Macaques That Were Transiently Viremic after Intravaginal Inoculation of SIV
• Direct ex vivo simian immunodeficiency virus (SIV)-specific cytotoxic activity detected from small intestine intraepithelial lymphocytes of SIV-infected macaques at an advanced stage of infection.
• Simian Immunodeficiency Virus (SIV) Infection of a Rhesus Macaque Induces SIV-Specific CD8+ T Cells with a Defect in Effector Function That Is Reversible on Extended Interleukin-2 Incubation
• Emergence and Kinetics of Simian Immunodeficiency Virus-Specific CD8+ T Cells in the Intestines of Macaques during Primary Infection