Characterization of T-Cell Responses in Macaques Immunized with a Single Dose of HIV DNA Vaccine

Arrode-Brusés, Géraldine; Sheffer, Darlene; Hegde, R. K.; Dhillon, Sukbir; Liu, Zhengian; Villinger, François; Narayan, Opendra; Chebloune, Yahia

doi:10.1128/jvi.01846-09

Cited by 11 publications

(21 citation statements)

References 65 publications

(80 reference statements)

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“…Our nonintegrating and non-persisting vaccine will hence induce similar responses that persist over a long period. Interestingly, similarly to the data that we reported earlier in both mice and macaque models, most proliferating CD8+ T cells induced by CAL-SHIV-IN − do not produce INF-␥ [31,43,77] but do produce the lytic compound Granzyme B as characteristics of cytotoxicity. We observed that at the early time points post immunization (week 2 and 4) almost equivalent response were detected against Gag, Env and TRN.…”

Section: Discusionsupporting

confidence: 86%

“…S3) indicate that Gag and TRN-specific T cell responses were mostly composed of proliferating CD3+ CD8+ T cells that increased by 3 fold from week 1 (5.9% of total CD8+ T cells) to week 2 (17.4% of total CD8+ T cells) post-immunization. The majority of these cells did not produce detectable level of IFN-␥ in this five days in vitro culture assay as we previously described [30,31]. Supplementary Fig.…”

Section: Immune Responses Induced In the Mouse Modelsmentioning

confidence: 68%

“…We demonstrated with our first generation of non-replicating and non-integrating DNA vaccine, 4SHIV-KU2, that a single dose immunization in the mouse and NHP models allowed the development of long-lasting and polyfunctional SHIVspecific T cell responses against Gag and other HIV antigens in immunized animals [29][30][31]. Importantly also, in earlier studies, macaques vaccinated with repeated doses of this DNA vaccine only, were protected from the challenge with SHIV89.6p [32][33][34].…”

Section: Introductionmentioning

confidence: 74%

See 2 more Smart Citations

A novel non-integrative single-cycle chimeric HIV lentivector DNA vaccine

Moussa

Arrode-Brusés

Manoylov

et al. 2015

Vaccine

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Section: Discusionsupporting

confidence: 86%

Section: Immune Responses Induced In the Mouse Modelsmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 74%

See 1 more Smart Citation

A novel non-integrative single-cycle chimeric HIV lentivector DNA vaccine

Moussa

Arrode-Brusés

Manoylov

et al. 2015

Vaccine

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“…Chlamydial-specific T cell expansion and cytokine production from PBMC was done as described (14). Briefly, CFSE (carboxy fluorescein succimidyl ester, Molecular Probes) labeled PBMCs were incubated at 2 x10 6 cell/ml in deep well tissue culture plates (96 well, Eppendorf) in 1 ml of AIM V medium (Life Technologies) only or pulsed with C. trachomatis A2497P + elementary bodies (EB) (MOI= 20) or chlamydial soluble antigen (SA) (100 μg/ml) and incubated for five days at 37°C and 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

CD8+ T Cells Define an Unexpected Role in Live-Attenuated Vaccine Protective Immunity against Chlamydia trachomatis Infection in Macaques

Olivares-Zavaleta

Whitmire

Kari

et al. 2014

The Journal of Immunology

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Trachoma, caused by the obligate intracellular organism Chlamydia trachomatis, is the world’s leading cause of preventable blindness for which a vaccine is needed. We have previously shown that a plasmid-deficient live-attenuated trachoma vaccine delivered ocularly to macaques elicited either solid or partial protective immunity against a virulent ocular challenge. Solidly protected macaques shared the same MHC class II alleles implicating CD4+ T cells in superior protective immunity. Understandably, we sought to define T cell immune correlates in these animals to potentially improve vaccine efficacy. Here, following a two year resting period, these macaques were boosted intramuscularly with the live-attenuated trachoma vaccine and their peripheral T cell anamnestic responses studied. Both solidly and partially protected macaques exhibited a CD4+ and CD8+ T cell anamnestic response following booster immunization. CD8+ but not CD4+ T cells from solidly protected macaques proliferated against soluble chlamydial antigen. We observed a more rapid T cell inflammatory cytokine response in tears of solidly protected animals following ocular re-challenge. Most notably, depletion of CD8+ T cells in solidly protected macaques completely abrogated protective immunity. Collectively, our findings support the conclusion that CD8+ T cells play an important but unexpected role in live-attenuated trachoma vaccine mediated protective immunity.

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“…Efforts were also made to enhance the immunogenicity of these vaccines by optimizing their delivery, the expression of viral antigens or targeting particular compartment in expressing cells. We have recently increased the dose of delivered DNA and characterized the immune responses induced by our HIV-DNA vaccine alone (Δ4-SHIV ku2 ) in immunized mice [15, 18] and macaques [20, 21]. We found, in both animal model studies that the responses to one high dose were made of long lasting and polyfunctional HIV-specific CD8 + T cells expressing Granzyme B endowed with high proliferating capacities.…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity of a lentiviral-based DNA vaccine driven by the 5′LTR of the naturally attenuated caprine arthritis encephalitis virus (CAEV) in mice and macaques

Arrode-Brusés¹,

Hegde²,

Jin³

et al. 2012

Vaccine

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Increasing the safety and the efficacy of existing HIV vaccines is one of the strategies that could help to promote the development of a vaccine for human use. We developed a HIV DNA vaccine (Δ4-SHIVku2) that has been shown to induce potent polyfunctional HIV-specific T cell responses following a single dose immunization of mice and macaques. Δ4-SHIVku2 also induced protection when immunized macaques were challenged with homologous pathogenic viruses. In the present study, our aim was to examine whether a chimeric HIV DNA vaccine (CAL-Δ4-SHIVku2) whose genome is driven by the LTR of the goat lentivirus, caprine arthritis encephalitis (CAEV) expresses efficiently the vaccine antigens and induces potent immune responses in animal models for HIV vaccine. Data of radioimmunoprecipitation assays clearly show that this chimeric genome drives efficient expression of all HIV antigens in the construct. In addition, evaluation of the p24 Gag protein in the supernatant of HEK-293-T cells transfected in parallel with Δ4-SHIVku2 and CAL-Δ4-SHIVku2 showed no difference suggesting that these two LTRs are inducing equally the expression of the viral genes. Immunization of mice and macaques using our single dose immunization regimen resulted in induction of similar IFN-γ ELISPOT responses in Δ4-SHIVku2- and CAL-Δ4-SHIVku2-treated mice. Similar profiles of T cell responses were also detected both in mice and macaques when multiparametric flow cytometry analyses were performed. Since CAEV LTR is not dependent of Tat to drive viral gene expression and is not functional for integration with HIV integrase, this new vector increases the safety and efficacy of our vaccine vectors and vaccination strategy.

show abstract

Characterization of T-Cell Responses in Macaques Immunized with a Single Dose of HIV DNA Vaccine

Cited by 11 publications

References 65 publications

A novel non-integrative single-cycle chimeric HIV lentivector DNA vaccine

A novel non-integrative single-cycle chimeric HIV lentivector DNA vaccine

CD8+ T Cells Define an Unexpected Role in Live-Attenuated Vaccine Protective Immunity against Chlamydia trachomatis Infection in Macaques

Immunogenicity of a lentiviral-based DNA vaccine driven by the 5′LTR of the naturally attenuated caprine arthritis encephalitis virus (CAEV) in mice and macaques

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