Extralymphoid CD8 ⁺ T Cells Resident in Tissue from Simian Immunodeficiency Virus SIVmac239Δnef-Vaccinated Macaques Suppress SIVmac239 Replication Ex Vivo

Abstract

Live-attenuated vaccination with simian immunodeficiency virus (SIV) SIVmac239⌬nef is the most successful vaccine product tested to date in macaques. However, the mechanisms that explain the efficacy of this vaccine remain largely unknown. We utilized an ex vivo viral suppression assay to assess the quality of the immune response in SIVmac239⌬nef-immunized animals. Using major histocompatibility complex-matched Mauritian cynomolgus macaques, we did not detect SIV-specific functional immune responses in the blood by gamma interferon (IFN-␥) enzyme-linked immunospot assay at select time points; however, we found that lung CD8 ؉ T cells, unlike blood CD8 ؉ T cells, effectively suppress virus replication by up to 80%. These results suggest that SIVmac239⌬nef may be an effective vaccine because it elicits functional immunity at mucosal sites. Moreover, these results underscore the limitations of relying on immunological measurements from peripheral blood lymphocytes in studies of protective immunity to HIV/SIV.

Conditional CD8+T Cell Escape during Acute Simian Immunodeficiency Virus Infection

“…Responses in BAL fluid samples were more robust than those in the blood samples (Fig. 1B and Table S1), consistent with earlier studies of SIV-specific CD8 ϩ T cell responses at this mucosal site (17).…”

Gag-Specific Cellular Immunity Determines In Vitro Viral Inhibition and In Vivo Virologic Control following Simian Immunodeficiency Virus Challenges of Vaccinated Rhesus Monkeys

“…CD8 ϩ T lymphocytes have been shown to be critical for the control of HIV-1 infection in persons with very low levels of plasma HIV-1 RNA in the absence of antiviral therapy (7,10,15,22,25). A similar observation has also been made in SIV-infected rhesus monkeys (8,9,12,14). For example, Hansen et al demonstrated in nonhuman primates that peak SIV-specific CD8 ϩ T lymphocyte responses following immunization were associated with virologic control in rhesus monkeys immunized with rhesus cytomegalovirus vaccines that included Gag antigens (9).…”

“…A wealth of literature has shown that CD8 ϩ T lymphocytes can mediate control of viremia in HIV-1-infected humans (2,7,10,11,22,25) and SIV-infected rhesus monkeys (8,9,23) and that T lymphocytes specific for HIV-1 Gag epitopes are associated with virologic control in vivo (4,5,13,15,26,28). Vaccine trials in nonhuman primates have also indicated an association between Gag-specific cellular immune responses and virologic control in vaccinated rhesus monkeys following SIV challenge (1,12,14,18,27).…”

Evaluation of humoral, mucosal, and cellular immune responses following co-immunization of HIV-1 Gag and Env proteins expressed by Newcastle disease virus

“…[8][9][10] Several studies have indicated that CD8 C T lymphocytes can control viremia in HIV-1 infected humans [11][12][13][14] and SIV infected monkeys. 11,[15][16][17][18] It has also been shown that CD8…”