scholarly journals MHC Heterozygote Advantage in Simian Immunodeficiency Virus-Infected Mauritian Cynomolgus Macaques

2010 ◽  
Vol 2 (22) ◽  
pp. 22ra18-22ra18 ◽  
Author(s):  
S. L. O'Connor ◽  
J. J. Lhost ◽  
E. A. Becker ◽  
A. M. Detmer ◽  
R. C. Johnson ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Heterozygote Advantage ◽  
Immunodeficiency Virus ◽  
Cynomolgus Macaques

scholarly journals Expansion of Simian Immunodeficiency Virus (SIV)-Specific CD8 T Cell Lines from SIV-Naive Mauritian Cynomolgus Macaques for Adoptive Transfer

2015 ◽  
Vol 89 (19) ◽  
pp. 9748-9757 ◽  
Author(s):  
Mariel S. Mohns ◽  
Justin M. Greene ◽  
Brian T. Cain ◽  
Ngoc H. Pham ◽  
Emma Gostick ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Simian Immunodeficiency Virus ◽  
Cell Lines ◽  
Cd8 T Cells ◽  
Adoptive Transfer ◽  
Cd8 T Cell ◽  
Immunodeficiency Virus ◽  
Cynomolgus Macaques ◽  
Transfer Strategies

ABSTRACTCD8 T cells play a crucial role in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). However, the specific qualities and characteristics of an effective CD8 T cell response remain unclear. Although targeting breadth, cross-reactivity, polyfunctionality, avidity, and specificity are correlated with HIV control, further investigation is needed to determine the precise contributions of these various attributes to CD8 T cell efficacy. We developed protocols for isolating and expanding SIV-specific CD8 T cells from SIV-naive Mauritian cynomolgus macaques (MCM). These cells exhibited an effector memory phenotype, produced cytokines in response to cognate antigen, and suppressed viral replicationin vitro. We further cultured cell lines specific for four SIV-derived epitopes, Nef103–111RM9, Gag389–394GW9, Env338–346RF9, and Nef254–262LT9. These cell lines were up to 94.4% pure, as determined by major histocompatibility complex (MHC) tetramer analysis. After autologous transfer into two MCM recipients, expanded CD8 T cells persisted in peripheral blood and lung tissue for at least 24 weeks and trafficked to multiple extralymphoid tissues. However, these cells did not impact the acute-phase SIV load after challenge compared to historic controls. The expansion and autologous transfer of SIV-specific T cells into naive animals provide a unique model for exploring cellular immunity and the control of SIV infection and facilitate a systematic evaluation of therapeutic adoptive transfer strategies for eradication of the latent reservoir.IMPORTANCECD8 T cells play a crucial role in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). Autologous adoptive transfer studies followed by SIV challenge may help define the critical elements of an effective T cell response to HIV and SIV infection. We developed protocols for isolating and expanding SIV-specific CD8 T cells from SIV-naive Mauritian cynomolgus macaques. This is an important first step toward the development of autologous transfer strategies to explore cellular immunity and potential therapeutic applications in the SIV model.

scholarly journals Changes in Soluble Factor-Mediated CD8+ Cell-Derived Antiviral Activity in Cynomolgus Macaques Infected with Simian Immunodeficiency Virus SIVmac251: Relationship to Biological Markers of Progression

2006 ◽  
Vol 80 (1) ◽  
pp. 236-245 ◽  
Author(s):  
Vincent Dioszeghy ◽  
Kadija Benlhassan-Chahour ◽  
Benoit Delache ◽  
Nathalie Dereuddre-Bosquet ◽  
Celine Aubenque ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Simian Immunodeficiency Virus ◽  
Clinical Stage ◽  
Soluble Factor ◽  
Cross Sectional ◽  
Cell Counts ◽  
Immunodeficiency Virus ◽  
Cynomolgus Macaques ◽  
Over Time

ABSTRACT Cross-sectional studies have shown that the capacity of CD8+ cells from human immunodeficiency virus (HIV)-infected patients and simian immunodeficiency virus (SIV) SIVmac-infected macaques to suppress the replication of human and simian immunodeficiency viruses in vitro depends on the clinical stage of disease, but little is known about changes in this antiviral activity over time in individual HIV-infected patients or SIV-infected macaques. We assessed changes in the soluble factor-mediated noncytolytic antiviral activity of CD8+ cells over time in eight cynomolgus macaques infected with SIVmac251 to determine the pathophysiological role of this activity. CD8+ cell-associated antiviral activity increased rapidly in the first week after viral inoculation and remained detectable during the early phase of infection. The net increase in antiviral activity of CD8+ cells was correlated with plasma viral load throughout the 15 months of follow-up. CD8+ cells gradually lost their antiviral activity over time and acquired virus replication-enhancing capacity. Levels of antiviral activity correlated with CD4+ T-cell counts after viral set point. Concentrations of β-chemokines and interleukin-16 in CD8+ cell supernatants were not correlated with this antiviral activity, and α-defensins were not detected. The soluble factor-mediated antiviral activity of CD8+ cells was neither cytolytic nor restricted to major histocompatibility complex. This longitudinal study strongly suggests that the increase in noncytolytic antiviral activity from baseline and the maintenance of this increase over time in cynomolgus macaques depend on both viral replication and CD4+ T cells.

scholarly journals Specific CD8+ T Cell Responses Correlate with Control of Simian Immunodeficiency Virus Replication in Mauritian Cynomolgus Macaques

2012 ◽  
Vol 86 (14) ◽  
pp. 7596-7604 ◽  
Author(s):  
M. L. Budde ◽  
J. M. Greene ◽  
E. N. Chin ◽  
A. J. Ericsen ◽  
M. Scarlotta ◽  
...  
Keyword(s):  
T Cell ◽  
Simian Immunodeficiency Virus ◽  
Virus Replication ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Cynomolgus Macaques

Preliminary report: protection of cynomolgus macaques against simian immunodeficiency virus by fixed infected-cell vaccine

The Lancet ◽  
1990 ◽  
Vol 336 (8730-8731) ◽  
pp. 1538-1541 ◽  
Author(s):  
E.J. Stott ◽  
F. Taffs ◽  
P. Kitchin ◽  
W.L. Chan ◽  
KHG Mills ◽  
...  
Keyword(s):  
Infected Cell ◽  
Simian Immunodeficiency Virus ◽  
Preliminary Report ◽  
Cell Vaccine ◽  
Immunodeficiency Virus ◽  
Cynomolgus Macaques

scholarly journals Mucosal Immunization of Cynomolgus Macaques with Two Serotypes of Live Poliovirus Vectors Expressing Simian Immunodeficiency Virus Antigens: Stimulation of Humoral, Mucosal, and Cellular Immunity

1999 ◽  
Vol 73 (11) ◽  
pp. 9485-9495 ◽  
Author(s):  
Shane Crotty ◽  
Barbara L. Lohman ◽  
Fabien X.-S. Lü ◽  
ShenBei Tang ◽  
Christopher J. Miller ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Simian Immunodeficiency Virus ◽  
Cytotoxic T Lymphocytes ◽  
Cytotoxic T Lymphocyte ◽  
Immunoglobulin A ◽  
Live Virus ◽  
Mucosal Antibody ◽  
Immunodeficiency Virus ◽  
Cynomolgus Macaques

ABSTRACT Poliovirus live virus vectors are a candidate recombinant vaccine system. Previous studies using this system showed that a live poliovirus vector expressing a foreign antigen between the structural and nonstructural proteins generates both antibody and cytotoxic T-lymphocyte responses in mice. Here we describe a novel in vitro method of cloning recombinant polioviruses involving a hybrid-PCR approach. We report the construction of recombinant vectors of two different serotypes of poliovirus-expressing simian immunodeficiency virus (SIV) antigens and the intranasal and intravenous inoculations of four adult cynomolgus macaques with these poliovirus vectors expressing the SIV proteins p17 gag and gp41 env . All macaques generated a mucosal anti-SIV immunoglobulin A (IgA) response in rectal secretions. Two of the four macaques generated mucosal antibody responses detectable in vaginal lavages. Strong serum IgG responses lasting for at least 1 year were detected in two of the four monkeys. SIV-specific T-cell lymphoproliferative responses were detected in three of the four monkeys. SIV-specific cytotoxic T lymphocytes were detected in two of the four monkeys. This is the first report of poliovirus-elicited vaginal IgA or cytotoxic T lymphocytes in any naturally infectable primate, including humans. These findings support the concept that a live poliovirus vector is a potentially useful delivery system that elicits humoral, mucosal, and cellular immune responses against exogenous antigens.

scholarly journals Multi-Low-Dose Mucosal Simian Immunodeficiency Virus SIVmac239 Challenge of Cynomolgus Macaques Immunized with “Hyperattenuated” SIV Constructs

2009 ◽  
Vol 84 (5) ◽  
pp. 2304-2317 ◽  
Author(s):  
David O. Willer ◽  
Yongjun Guan ◽  
Mark A. Luscher ◽  
Bing Li ◽  
Rick Pilon ◽  
...  
Keyword(s):  
Viral Load ◽  
Simian Immunodeficiency Virus ◽  
Low Dose ◽  
Vaccine Group ◽  
Cell Counts ◽  
Immunodeficiency Virus ◽  
Cynomolgus Macaques ◽  
Peak Viral Load ◽  
Viral Load Set Point

ABSTRACT Hyperattenuated simian immunodeficiency virus SIVmac239-derived constructs Δ5-CMV and Δ6-CCI are an effort to render SIV incapable of, in practical terms, both reversion and recombination while maintaining the immune features of SIV as a retrovirus. Primary inoculation of cynomolgus macaques with 108 50% tissue culture infective doses (TCID50) of Δ5-CMV or Δ6-CCI induced low-level humoral and cellular responses detectable in the absence of measureable in vivo replication. The first of three DNA boosts resulted in elevated gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) responses to Gag, Pol, and Env in the Δ5-CMV vaccine group compared to the Δ6-CCI vaccine group (P = 0.001). Weekly intrarectal challenge with a low dose of SIVmac239 followed by a dose escalation was conducted until all animals became infected. The mean peak viral load of the Δ5-CMV-vaccinated animals (3.7 × 105 copies/ml) was ∼1 log unit lower than that of the control animals. More dramatically, the viral load set point of these animals was decreased by 3 log units compared to that of the controls (<50 versus 1.64 × 104 copies/ml; P < 0.0001). Seventy-five percent (6/8) of vaccine recipients controlled virus below 1,000 copies/ml for at least 6 months, with a subset controlling virus and maintaining substantial CD4 T-cell counts for close to 2 years of follow-up. The correlates of protection from SIV disease progression may lie in the rapidity and protective value of immune responses that occur early in primary SIV infection. Prior immunization with hyperattenuated SIVmac239, even if sterilizing immunity is not achieved, may allow a more advantageous host response.

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