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Transcriptional profiles of unfractionated lymph nodes cells obtained from completely protected, non protected and unvaccinated control rhesus macaques seven days prior to, and four and fourteen days after wt SIVmac239 challenge by microarray analysis.

ABSTRACT: Live-attenuated SIV vaccines (LAVs) remain the most efficacious of all vaccines in nonhuman primate models of HIV/AIDS, yet the basis of their robust protection remains poorly understood. Here, we demonstrate that the degree of LAV-mediated protection against intravenous (IV) wildtype (wt) SIVmac239 challenge strongly correlates with the magnitude and function of SIV-specific, effector-differentiated T cells in lymph node (LN), but not with such T cell responses in blood or with other cellular, humoral and innate immune parameters. Maintenance of protective T cell responses was associated with persistent LAV replication in LN, which occurred almost exclusively in follicular helper T cells. Thus, effective LAVs maintain lymphoid tissue-based, effector-differentiated, SIV-specific T cells that intercept and suppress early wt SIV amplification and, if present in sufficient frequencies, can completely control and perhaps clear infection -- an observation that provides rationale for development of safe, persistent vectors that can elicit and maintain such responses.

ORGANISM(S): Homo sapiens Macaca mulatta

PROVIDER: GSE39967 | GEO | 2012/08/09

SECONDARY ACCESSION(S): PRJNA172175

REPOSITORIES: GEO

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Transcriptional profiles of unfractionated lymph nodes cells obtained from completely protected, non protected and unvaccinated control rhesus macaques seven days prior to, and four and fourteen days after wt SIVmac239 challenge by microarray analysis.

Project description:Live-attenuated SIV vaccines (LAVs) remain the most efficacious of all vaccines in nonhuman primate models of HIV/AIDS, yet the basis of their robust protection remains poorly understood. Here, we demonstrate that the degree of LAV-mediated protection against intravenous (IV) wildtype (wt) SIVmac239 challenge strongly correlates with the magnitude and function of SIV-specific, effector-differentiated T cells in lymph node (LN), but not with such T cell responses in blood or with other cellular, humoral and innate immune parameters. Maintenance of protective T cell responses was associated with persistent LAV replication in LN, which occurred almost exclusively in follicular helper T cells. Thus, effective LAVs maintain lymphoid tissue-based, effector-differentiated, SIV-specific T cells that intercept and suppress early wt SIV amplification and, if present in sufficient frequencies, can completely control and perhaps clear infection -- an observation that provides rationale for development of safe, persistent vectors that can elicit and maintain such responses. There are four protection outcome groups: unvaccinated control (C), complete protect (CP), non-protect (NP) and partial protect (PP). Respectively for these groups, there are 7, 9, 6 and 4 animals sampled seven days pre-challenge (minus7PCD); 9, 13, 5 and 5 animals sampled four days post-challenge (4PCD) and 8, 11, 5 and 3 fourteen days post-challenge (14PCD).

2012-08-08 | E-GEOD-39967 | biostudies-arrayexpress

Transcriptional profiles of sorted CD8+ and CD4+ memory T cells from CP and NP and unvaccinated control RM 7 days prior to, and 4 and 14 days after wt SIVmac239 challenge by microarray analysis.

Project description:Live-attenuated SIV vaccines (LAVs) remain the most efficacious of all vaccines in nonhuman primate models of HIV/AIDS, yet the basis of their robust protection remains poorly understood. Here, we demonstrate that the degree of LAV-mediated protection against intravenous (IV) wildtype (wt) SIVmac239 challenge strongly correlates with the magnitude and function of SIV-specific, effector-differentiated T cells in lymph node (LN), but not with such T cell responses in blood or with other cellular, humoral and innate immune parameters. Maintenance of protective T cell responses was associated with persistent LAV replication in LN, which occurred almost exclusively in follicular helper T cells. Thus, effective LAVs maintain lymphoid tissue-based, effector-differentiated, SIV-specific T cells that intercept and suppress early wt SIV amplification and, if present in sufficient frequencies, can completely control and perhaps clear infection -- an observation that provides rationale for development of safe, persistent vectors that can elicit and maintain such responses. There are two protection outcome groups, complete protect (CP) and non-protect (NP) animals. Memory T cells (CD4+ or CD8+) were sorted for three time points, seven days pre-challenge, four days post-challenge and fourteen days post-challenge.

2012-08-08 | E-GEOD-39968 | biostudies-arrayexpress

Transcriptional profiles of sorted CD8+ and CD4+ memory T cells from CP and NP and unvaccinated control RM 7 days prior to, and 4 and 14 days after wt SIVmac239 challenge by microarray analysis.

2012-08-09 | GSE39968 | GEO

Elucidating the Onset of Cross-protective Immunity after Intranasal Vaccination with the Attenuated African Swine Fever Vaccine Candidate BA71ΔCD2

Project description:African swine fever (ASF) is a deadly disease of swine currently causing a worldwide pandemic leading to severe economic consequences for the porcine industry. The control of disease spread is hampered by the limitation of available effective vaccines. Live attenuated vaccines (LAVs) are currently the most advanced vaccine prototypes, providing strong protection against ASF. However, the significant advances achieved using LAVs must be complemented with further studies to analyse vaccine-induced immunity. Here we characterized the onset of cross-protective immunity triggered by the LAV candidate BA71ΔCD2. Intranasally vaccinated pigs were challenged with the virulent Georgia 2007/1 strain at days 3, 7 and 12 postvaccination. Only the animals vaccinated 12 days before challenge effectively controlled infection progression, showing low virus loads, minor clinical signs and lack of the unbalanced inflammatory response characteristic of severe disease. Contrarily, animals vaccinated 3 or 7 days before challenge just showed a minor delay of disease progression. Virus-specific antibody responses and whole blood transcriptome signatures demonstrated that control of infection is associated with the presence of virus-specific antibodies and a cytotoxic response before challenge. These results contribute to our understanding of protective immunity induced by LAV-based vaccines, encouraging their use in emergency responses in ASF affected areas.

2024-05-08 | GSE266565 | GEO

Transcriptome Profiles of Gag-Specific CD8+ T Cells Induced by Live Attenuated SIV Vaccine

Project description:SIVmac239Δnef (SIVΔnef) live attenuated vaccine (LAV) induces the best protection among all the vaccine modalities tested in rhesus macaque model of HIV-1 infection. Time-dependent protection is a unique feature of this vaccine: macaques are not protected at 3-5 weeks post vaccination (WPV), whereas immune protection emerges between 15 and 20 WPV. To elucidate the protection mechanisms induced by SIVΔnef vaccine, we longitudinally compared the global gene expression profiles of SIV Gag-CM9+ CD8+ (Gag-specific CD8+) T cells from peripheral blood of Mamu-A*01 rhesus macaques at 3 and 20 WPV using rhesus microarray. We found that gene expression profiles of Gag-specific CD8+ T cells at 20 WPV are qualitatively different from those at 3 WPV. At 20 WPV, the most significant transcriptional changes of Gag-specific CD8+ T cells were genes involved in cell activation, differentiation and maturation toward central memory cells. Our study indicates that a higher quality of SIV-specific CD8+ T cells elicited by SIVΔnef over time may contribute to the maturation of time dependent protection.

2015-12-02 | GSE75567 | GEO

Interleukin-10 regulates reservoir establishment and persistence in antiretroviral therapy-treated, SIV-infected macaques

Project description:Interleukin (IL)-10 is an immunosuppressive cytokine that signals through STAT3 to regulate T follicular helper cell (TFH) differentiation and germinal center formation, which we propose acts as a determinant of HIV/SIV persistence. In SIV-infected macaques, levels of IL-10 in plasma and lymph node (LN) are induced by infection and not normalized with ART. During chronic infection, plasma IL-10 and transcriptomic signatures of IL-10 signaling were significantly correlated with the cell-associated SIV-DNA content within LN CD4+ memory subsets, including TFH, and predicted the frequency of CD4+ TFH and their cell-associated SIV-DNA content during ART, respectively. Notably, in ART-treated RMs, cells harboring SIV-DNA by DNAscope were preferentially found in the LN B-cell follicle in close proximity to IL-10. Finally, we demonstrate that the in vivo neutralization of soluble IL-10 in ART-treated, SIV-infected macaques significantly reduces B cell follicle maintenance and, by extension, cellular sites of viral persistence, including LN TFH and memory CD4+ T-cells expressing PD-1 and CTLA-4. Thus, these data support a role for IL-10 in maintaining a pool of target cells in lymphoid tissue that serve as a niche for viral persistence. Targeting IL-10 signaling to impair CD4+ T-cell survival and improve antiviral immune responses may represent a novel approach to limit viral persistence in ART-suppressed people living with HIV.

2022-02-09 | GSE196436 | GEO

Interleukin-10 contributes to reservoir establishment and persistence in antiretroviral therapy-treated, SIV-infected macaques

Project description:Interleukin (IL)-10 is an immunosuppressive cytokine that signals through STAT3 to regulate T follicular helper cell (TFH) differentiation and germinal center formation. In SIV-infected macaques, levels of IL-10 in plasma and lymph node (LN) are induced by infection and not normalized with ART. During chronic infection, plasma IL-10 and transcriptomic signatures of IL-10 signaling were significantly correlated with the cell-associated SIV-DNA content within LN CD4+ memory subsets, including TFH, and predicted the frequency of CD4+ TFH and their cell- associated SIV-DNA content during ART, respectively. Notably, in ART-treated RMs, cells harboring SIV-DNA by DNAscope were preferentially found in the LN B-cell follicle in close proximity to IL-10. Finally, we demonstrate that the in vivo neutralization of soluble IL-10 in ART-treated, SIV-infected macaques significantly reduces B cell follicle maintenance and, by extension, cellular sites of viral persistence, including LN TFH and memory CD4+ T-cells expressing PD-1 and CTLA-4. Thus, these data support a role for IL-10 in maintaining a pool of target cells in lymphoid tissue that serve as a niche for viral persistence. Targeting IL-10 signaling to impair CD4+ T-cell survival and improve antiviral immune responses may represent a novel approach to limit viral persistence in ART-suppressed people living with HIV.

2022-02-09 | GSE196182 | GEO

Correlates of protection against SIVmac239 infection in rhesus macaques immunized with chimpanzee-derived adenovirus vectors

Project description:An efficacious vaccine to HIV-1 remains elusive. We tested two vaccine regimens based on prime-boosting with two chimpanzee-origin adenovirus (Ad) vectors (SAdV) of serotypes SAdV24 and SAdV23 or two distinct human serotype Ad vectors (HAdV), i.e., HAdV5 and HAdV26, expressing Gag and gp160 of SIVmac239 for induction of protection against repeated low dose rectal SIVmac251 challenges in Indian rhesus macaques (RMs). Animals were rendered seropositive to the HAdV vectors prior to vaccination. In RMs with non-controller genotypes, the SAdV vectors achieved significant reduction in viral acquisition. In RMs with controller genotypes, both vaccine regimens reduced set-point and peak viral loads and accelerated viral clearance. In SAdV-vaccinated RMs resistance against infection correlated with levels of circulating envelope (Env)-specific antibody (Ab) titers. In both vaccine groups CD8+T cells controlled viral loads upon infection. Circulating CD4+ and CD8+ T cells showed significant changes in their transcriptome over time following vaccination, which differed between the vaccine groups. T cells from SIV-resistant RMs had unique transcriptional profiles indicating that both follicular T helper (TFH) cell responses and highly activated CD8+ T cells may play a role in protection. Our results demonstrate that SAdV-based candidate AIDS vaccines provide protection from virus acquisition and replication in a stringent SIV challenge model in RMs and may thus outperform HIV-1 vaccines that have undergone large-scale clinical efficacy testing in humans.

2019-05-21 | GSE102115 | GEO

IL-21 and IFNalpha therapy rescues terminally-differentiated NK cells and limit SIV reservoir in ART-treated macaques [cohort3]

Project description:Unlike HIV infection, which progresses to AIDS absent suppressive anti-retroviral therapy (ART), nonpathogenic infections in natural hosts, such African green monkeys (AGMs), are characterized by a lack of gut microbial translocation and robust secondary lymphoid Natural Killer (NK) cell responses resulting in absence of chronic inflammation and limited SIV dissemination in lymph nodes (LN) B-cell-follicles, respectively. In a pathogenic infection model (i.e. ART-treated, SIVmac239-infected rhesus macaques; RMs), sequential Interleukin (IL)-21 and interferon (IFN)-alpha therapy generated terminally-differentiated blood NK cells (NKG2a/clowCD16+) with potent HLA-E-restricted activity in response to SIV-ENV peptides in contrast to control RMs, where less differentiated, IFN-gamma+ NK cells predominated. The frequency and cytolytic activity of NKG2a/clowCD16+ NK cells correlated with a reduction of replication-competent SIV in LN during ART and viral rebound delay following analytical treatment interruption. These data demonstrate that AGM-like NK cell differentiation profiles can be rescued in RMs to promote viral clearance in tissues.

2021-02-22 | GSE163442 | GEO

IL-21 and IFNalpha therapy rescues terminally-differentiated NK cells and limit SIV reservoir in ART-treated macaques [cohort2]

2021-02-22 | GSE163441 | GEO

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