Mucosal immunization with a live, virulence-attenuated simian immunodeficiency virus (SIV) vaccine elicits antiviral cytotoxic T lymphocytes and antibodies in rhesus macaques

1994 ◽  
Vol 23 (2-3) ◽  
pp. 95-101 ◽  
Author(s):  
Barbara L. Lohman ◽  
Micheal B. McChesney ◽  
Christopher J. Miller ◽  
Moses Otsyula ◽  
Christopher J. Berardi ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Simian Immunodeficiency Virus ◽  
Cytotoxic T Lymphocytes ◽  
Rhesus Macaques ◽  
Mucosal Immunization ◽  
Immunodeficiency Virus

scholarly journals CD8+ Lymphocytes Do Not Mediate Protection against Acute Superinfection 20 Days after Vaccination with a Live Attenuated Simian Immunodeficiency Virus

2005 ◽  
Vol 79 (19) ◽  
pp. 12264-12272 ◽  
Author(s):  
Richard Stebbings ◽  
Neil Berry ◽  
Herman Waldmann ◽  
Pru Bird ◽  
Geoff Hale ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Lymphocytes ◽  
Simian Immunodeficiency Virus ◽  
Cytotoxic T Lymphocytes ◽  
T Lymphocyte ◽  
Lymphoid Tissue ◽  
Human Immunoglobulin ◽  
Wild Type ◽  
Lymphocyte Depletion ◽  
Immunodeficiency Virus

ABSTRACT In order to test the hypothesis that CD8+ cytotoxic T lymphocytes mediate protection against acute superinfection, we depleted >99% of CD8+ lymphocytes in live attenuated simian immunodeficiency virus macC8 (SIVmacC8) vaccinees from the onset of vaccination, maintained that depletion for 20 days, and then challenged with pathogenic, wild-type SIVmacJ5. Vaccinees received 5 mg per kg of humanized anti-CD8 monoclonal antibody (MAb) 1 h before inoculation, followed by the same dose again on days 3, 7, 10, 13, and 17. On day 13, peripheral CD8+ T lymphocytes were >99% depleted in three out of four anti-CD8 MAb-treated vaccinees. At this time attenuated SIVmacC8 viral RNA loads in anti-CD8 MAb-treated vaccinees were significantly higher than control vaccinees treated contemporaneously with nonspecific human immunoglobulin. Lymphoid tissue CD8+ T lymphocyte depletion was >99% in three out of four anti-CD8 MAb-treated vaccinees on the day of wild-type SIVmacJ5 challenge. All four control vaccinees and three out of four anti-CD8 MAb-treated vaccinees were protected against detectable superinfection with wild-type SIVmacJ5. Although superinfection with wild-type SIVmacJ5 was detected at postmortem in a single anti-CD8 MAb-treated vaccinee, this did not correlate with the degree of preceding CD8+ T lymphocyte depletion. Clearance of attenuated SIVmacC8 viremia coincided with recovery of normal CD8+ T lymphocyte counts between days 48 and 76. These results support the view that cytotoxic T lymphocytes are important for host-mediated control of SIV primary viremia but do not indicate a central role in protection against acute superinfection conferred by inoculation with live attenuated SIV.

scholarly journals Elicitation of Simian Immunodeficiency Virus-Specific Cytotoxic T Lymphocytes in Mucosal Compartments of Rhesus Monkeys by Systemic Vaccination

2002 ◽  
Vol 76 (22) ◽  
pp. 11484-11490 ◽  
Author(s):  
Jamal Baig ◽  
Daniel B. Levy ◽  
Paul F. McKay ◽  
Joern E. Schmitz ◽  
Sampa Santra ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Cytotoxic T Lymphocytes ◽  
Rhesus Monkeys ◽  
Hiv Infections ◽  
Systemic Delivery ◽  
Mucosal Tissues ◽  
Immunodeficiency Virus ◽  
Ctl Responses

ABSTRACT Since most human immunodeficiency virus (HIV) infections are initiated following mucosal exposure to the virus, the anatomic containment or abortion of an HIV infection is likely to require vaccine-elicited cellular immune responses in those mucosal sites. Studying vaccine-elicited mucosal immune responses has been problematic because of the difficulties associated with sampling T lymphocytes from those anatomic compartments. In the present study, we demonstrate that mucosal cytotoxic T lymphocytes (CTL) specific for simian immunodeficiency virus (SIV) and simian HIV can be reproducibly sampled from intestinal mucosal tissue of rhesus monkeys obtained under endoscopic guidance. These lymphocytes recognize peptide-major histocompatibility complex class I complexes and express gamma interferon on exposure to peptide antigen. Interestingly, systemic immunization of monkeys with plasmid DNA immunogens followed by live recombinant attenuated poxviruses or adenoviruses with genes deleted elicits high-frequency SIV-specific CTL responses in these mucosal tissues. These studies therefore suggest that systemic delivery of potent HIV immunogens may suffice to elicit substantial mucosal CTL responses.

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 Inhibition of Simian Immunodeficiency Virus (SIV) Replication by CD8+ T Lymphocytes from Macaques Immunized with Live Attenuated SIV

1998 ◽  
Vol 72 (8) ◽  
pp. 6315-6324 ◽  
Author(s):  
Marie-Claire Gauduin ◽  
Rhona L. Glickman ◽  
Robert Means ◽  
R. Paul Johnson
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Simian Immunodeficiency Virus ◽  
Cytotoxic T Lymphocyte ◽  
Rhesus Macaques ◽  
Hiv Replication ◽  
Inhibitory Protein ◽  
Soluble Factors ◽  
Immunodeficiency Virus ◽  
Vaccine Approach

ABSTRACT Characterization of immune responses induced by live attenuated simian immunodeficiency virus (SIV) strains may yield clues to the nature of protective immunity induced by this vaccine approach. We investigated the ability of CD8+ T lymphocytes from rhesus macaques immunized with the live, attenuated SIV strain SIVmac239Δnef or SIVmac239Δ3 to inhibit SIV replication. CD8+ T lymphocytes from immunized animals were able to potently suppress SIV replication in autologous SIV-infected CD4+ T cells. Suppression of SIV replication by unstimulated CD8+ T cells required direct contact and was major histocompatibility complex (MHC) restricted. However, CD3-stimulated CD8+ T cells produced soluble factors that inhibited SIV replication in an MHC-unrestricted fashion as much as 30-fold. Supernatants from stimulated CD8+ T cells were also able to inhibit replication of both CCR5- and CXCR4-dependent human immunodeficiency virus type 1 (HIV-1) strains. Stimulation of CD8+ cells with cognate cytotoxic T-lymphocyte epitopes also induced secretion of soluble factors able to inhibit SIV replication. Production of RANTES, macrophage inhibitory protein 1α (MIP-1α), or MIP-1β from stimulated CD8+ T cells of vaccinated animals was almost 10-fold higher than that from stimulated CD8+ T cells of control animals. However, addition of antibodies that neutralize these β-chemokines, either alone or in combination, only partly blocked inhibition of SIV and HIV replication by soluble factors produced by stimulated CD8+ T cells. Our results indicate that inhibition of SIV replication by CD8+ T cells from animals immunized with live attenuated SIV strains involves both MHC-restricted and -unrestricted mechanisms and that MHC-unrestricted inhibition of SIV replication is due principally to soluble factors other than RANTES, MIP-1α, and MIP-1β.

scholarly journals Decreased Frequency of Cytomegalovirus (CMV)-Specific CD4+ T Lymphocytes in Simian Immunodeficiency Virus-Infected Rhesus Macaques: Inverse Relationship with CMV Viremia

2002 ◽  
Vol 76 (8) ◽  
pp. 3646-3658 ◽  
Author(s):  
Amitinder Kaur ◽  
Corrina L. Hale ◽  
Bradley Noren ◽  
Nadine Kassis ◽  
Meredith A. Simon ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Simian Immunodeficiency Virus ◽  
Inverse Relationship ◽  
Rhesus Macaques ◽  
Intracellular Cytokine Staining ◽  
Median Frequency ◽  
Intracellular Cytokine ◽  
Immunodeficiency Virus ◽  
Siv Infection ◽  
Limiting Dilution

ABSTRACT The frequency of cytomegalovirus (CMV)-specific CD4+ T lymphocytes was determined in CMV-seropositive rhesus macaques with or without simian immunodeficiency virus (SIV) infection by using the sensitive assays of intracellular cytokine staining and gamma interferon ELISPOT. Both techniques yielded 3- to 1,000-fold-higher frequencies of CMV-specific CD4+ T lymphocytes than traditional proliferative limiting dilution assays. The median frequency of CMV-specific CD4+ T lymphocytes in 23 CMV-seropositive SIV-negative macaques was 0.63% (range, 0.16 to 5.8%). The majority of CMV-specific CD4+ T lymphocytes were CD95pos and CD27lo but expressed variable levels of CD45RA. A significant reduction (P < 0.05) in the frequency of CMV-specific CD4+ T lymphocytes was observed in pathogenic SIV-infected macaques but not in macaques infected with live attenuated strains of SIV. CMV-specific CD4+ T lymphocytes were not detected in six of nine pathogenic SIV-infected rhesus macaques. CMV DNA was detected in the plasma of four of six of these macaques but in no animal with detectable CMV-specific CD4+ T lymphocytes. In pathogenic SIV-infected macaques, loss of CMV-specific CD4+ T lymphocytes was not predicted by the severity of CD4+ T lymphocytopenia. Neither was it predicted by the pre-SIV infection frequencies of CD45RAneg or CCR5pos CMV-specific CD4+ T lymphocytes. However, the magnitude of activation, as evidenced by the intensity of CD40L expression on CMV-specific CD4+ T lymphocytes pre-SIV infection, was three- to sevenfold greater in the two macaques that subsequently lost these cells after SIV infection than in the two macaques that retained CMV-specific CD4+ T lymphocytes post-SIV infection. Future longitudinal studies with these techniques will facilitate the study of CMV pathogenesis in AIDS.

scholarly journals Decline of Simian Immunodeficiency Virus (SIV)–Specific Cytotoxic T Lymphocytes in the Peripheral Blood of Long‐Term Nonprogressing Macaques Infected with SIVmac32H‐J5

1999 ◽  
Vol 180 (4) ◽  
pp. 1133-1141 ◽  
Author(s):  
Anna‐Maria Geretti ◽  
Ellen G. J. Hulskotte ◽  
Marlinda E. M. Dings ◽  
Carel A. van Baalen ◽  
Geert van Amerongen ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Simian Immunodeficiency Virus ◽  
Cytotoxic T Lymphocytes ◽  
Peripheral Blood ◽  
Immunodeficiency Virus

scholarly journals Viral Escape from Dominant Simian Immunodeficiency Virus Epitope-Specific Cytotoxic T Lymphocytes in DNA-Vaccinated Rhesus Monkeys

2003 ◽  
Vol 77 (13) ◽  
pp. 7367-7375 ◽  
Author(s):  
Dan H. Barouch ◽  
Jennifer Kunstman ◽  
Jennifer Glowczwskie ◽  
Kevin J. Kunstman ◽  
Michael A. Egan ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Viral Replication ◽  
Simian Immunodeficiency Virus ◽  
Cytotoxic T Lymphocytes ◽  
Rhesus Monkeys ◽  
Viral Rna ◽  
Viral Escape ◽  
Effective Control ◽  
Immunodeficiency Virus ◽  
Dominant Epitope

ABSTRACT Virus-specific cytotoxic T lymphocytes (CTL) are critical for control of human immunodeficiency virus type 1 replication. However, viral escape from CTL recognition can undermine this immune control. Here we demonstrate the high frequency and pattern of viral escape from dominant epitope-specific CTL in SIV gag DNA-vaccinated rhesus monkeys following a heterologous simian immunodeficiency virus (SIV) challenge. DNA-vaccinated monkeys exhibited initial effective control of the SIV challenge, but this early control was lost by serial breakthroughs of viral replication over a 3-year follow-up period. Increases in plasma viral RNA correlated temporally with declines of dominant SIV epitope-specific CD8+ T-lymphocyte responses and the emergence of viral mutations that escaped recognition by dominant epitope-specific CTL. Viral escape from CTL occurred in a total of seven of nine vaccinated and control monkeys, including three animals that initially controlled viral replication to undetectable levels of plasma viral RNA. These data suggest that CTL exert selective pressure on viral replication and that viral escape from CTL may be a limitation of CTL-based AIDS vaccine strategies.

scholarly journals Effects of Cytotoxic T Lymphocytes (CTL) Directed against a Single Simian Immunodeficiency Virus (SIV) Gag CTL Epitope on the Course of SIVmac239 Infection

2002 ◽  
Vol 76 (20) ◽  
pp. 10507-10511 ◽  
Author(s):  
Todd M. Allen ◽  
Peicheng Jing ◽  
Briana Calore ◽  
Helen Horton ◽  
David H. O'Connor ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Lymphocytes ◽  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Cytotoxic T Lymphocytes ◽  
Ctl Epitope ◽  
Immunodeficiency Virus ◽  
The Impact ◽  
Sivmac239 Infection ◽  
Ctl Responses

ABSTRACT Vaccine-induced cytotoxic T lymphocytes (CTL) have been implicated in the control of virus replication in simian immunodeficiency virus (SIV)-challenged and simian-human immunodeficiency virus-challenged macaques. Therefore, we wanted to test the impact that vaccine-induced CTL responses against an immunodominant Gag epitope might have in the absence of other immune responses. By themselves, these strong CTL responses failed to control SIVmac239 replication.

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