Immune Responses following Neonatal DNA Vaccination Are Long-Lived, Abundant, and Qualitatively Similar to Those Induced by Conventional Immunization

Hassett, Daniel E.; Zhang, Jie; Slifka, Mark K.; Whitton, J. Lindsay

doi:10.1128/jvi.74.6.2620-2627.2000

Cited by 78 publications

(52 citation statements)

References 46 publications

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“…6 Much less information is available on cellular immunity. Hassett et al 7 reported that antigenspecific CD8 + T cells remained detectable at 1 year after vaccination by directly measuring the presence of peptide-specific CD8 + T cells, also similar to the present results. The mechanism of their persistence is unknown Gene Therapy at present.…”

Section: Discussionsupporting

confidence: 91%

“…While DNA vaccines induce CD8 + cytotoxic T lymphocytes (CTL) specific for peptides derived from plasmid-encoded molecules, detailed analysis of the kinetics of CD8 + T cells induced by vaccinations is still limited. 7,8 We have recently demonstrated in a murine syngeneic tumor system that 9mer peptide, murine HER2p63 (TYLPANASL), can induce CD8 + CTLs with MHC class I, K d restriction and more importantly, can be a target for in vivo tumor-rejection immune responses. [9][10][11] HLA-A2402, which is expressed by more than 60% of the Japanese population and also by a significant proportion of individuals in other countries, shares a similar peptidebinding motif with murine MHC class I, K d .…”

Section: Introductionmentioning

confidence: 99%

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HER2 peptide-specific CD8+ T cells are proportionally detectable long after multiple DNA vaccinations

et al. 2002

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

HER2 peptide-specific CD8+ T cells are proportionally detectable long after multiple DNA vaccinations

et al. 2002

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“…Thus, CD8 ϩ responses can be primed by a DNA vaccine, and memory CD8 ϩ T cells remain detectable directly ex vivo for 30 days postinjection (ϳ0.7% of all splenic CD8 ϩ T cells) (Fig. 1); this proportion of antigen-specific memory cells is maintained and can confer protective immunity, for at least a year after pCM-VNP immunization (10).…”

Section: Resultsmentioning

confidence: 99%

“…CTL assays were carried out as previously described (10). ICCS and flow cytometric analysis of antigen-specific T-cell responses.…”

Section: Methodsmentioning

confidence: 99%

Direct Ex Vivo Kinetic and Phenotypic Analyses of CD8⁺T-Cell Responses Induced by DNA Immunization

Hassett

Zhang

Whitton

2000

J Virol

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In many natural infections and experimental models, virusspecific CD8 ϩ T cells are critical for clearance of primary virus infection and for subsequent protective immunity. In addition, these cells are an important component of the immunity conferred by attenuated and recombinant viruses and by plasmid DNA vaccines. Although the kinetics of the antiviral CD8 ϩ T-cell response during the inductive and memory phases of certain systemic viral infections have been well characterized (8,16,19), there is little detailed knowledge about the kinetics of cellular immunity induced by conventional vaccines or by DNA immunization. Of particular interest is how rapidly CD8 ϩ T-cell responses develop after vaccination, as these cells play a critical role in limiting virus replication.Although a number of groups have independently demonstrated DNA vaccine-induced antigen-specific CD8 ϩ T cells in a variety of animal models (1,6,12,14,18,24,26,31) as well as in humans (29), the kinetics and functional attributes of these responses have not been fully characterized. In particular, most DNA vaccine studies to date have employed in vitro cytotoxicity assays to detect CD8 ϩ T-cell responses, but these assays are not sufficiently sensitive to permit the direct ex vivo detection of DNA-induced cytotoxic T lymphocytes (CTLs); consequently, DNA-induced CTLs have been extensively restimulated in vivo or in vitro to expand their numbers to a detectable level. It has therefore been difficult to confidently enumerate the CD8 ϩ T cells in a DNA-vaccinated host. Here we employ a more sensitive technique, intracellular cytokine staining (ICCS), to detect CD8 ϩ T-cell responses, thereby avoiding the need for lengthy restimulation. In this way, we have been able to measure DNA-induced CD8 ϩ T-cell numbers directly ex vivo at various times after a single inoculation of plasmid DNA. Using a well-defined murine model of viral pathogenesis and immunity, infection with the arenavirus lymphocytic choriomeningitis virus (LCMV), we have examined the temporal kinetics and functional attributes of CD8 ϩ T cells induced by DNA vaccination and compared them to the responses induced by LCMV infection and by immunization with a recombinant vaccinia virus vaccine. We have also determined how rapidly a DNA vaccine can induce protective antiviral immunity. MATERIALS AND METHODSMice. BALB/c mice were purchased from the Scripps Research Institute animal facility and housed in specific-pathogen-free conditions. Mice were used between 4 and 16 weeks of age.Viruses and viral infections. Stocks of the Armstrong strain of LCMV were grown on BHK cells in RPMI containing 10% fetal bovine serum (FBS), penicillin G (50 U/liter), streptomycin (50 g/liter), and 20 mM L-glutamine (all from Gibco-BRL, Rockville, Md.). LCMV titers were determined by plaque assay on Vero cells grown in medium 199 (Gibco-BRL) containing 5% FBS, penicillin G (50 U/liter), streptomycin (50 g/liter), 20 mM L-glutamine, and 0.5% agarose as previously described (11). Mice were infected by the intrap...

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“…Since protective immunity seemed to correlate with CMI rather than humoral immune responses (8), a major effort was focused on examination of the potential of DNA vaccines to induce this type of immune response because plasmid DNA-expressing viral genes together with the CpG motifs are known to be potent inducers of CMI responses (9). Current HIV-1 DNA vaccines consist of one or more HIV genes whose expression is regulated by the CMV promoter.…”

mentioning

confidence: 99%

Phenotypic and Functional Analysis of Immune CD8+ T Cell Responses Induced by a Single Injection of a HIV DNA Vaccine in Mice

Arrode

Hegde

Mani

et al. 2007

The Journal of Immunology

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HIV DNA vaccines are potent inducers of cell-mediated immune (CMI) response in mice but elicit poor HIV-specific IFN-γ-producing T cells in monkeys and humans. In this study, we performed kinetic analyses on splenocytes of BALB/c mice that were immunized by a single injection with a unique DNA vaccine. Using IFN-γ-ELISPOT and multiparametric FACS analysis, we characterized the induced CMI response. We found that the response was detectable for at least 63 wk. ELISPOT detection of IFN-γ-producing T cells showed a profile with two waves separated by a long period of minimal response. Multiparametric FACS analysis showed two populations of CD3+CD8+ T cells that were specific for all HIV Ags. These cells had similar robust proliferation abilities and contained granzyme B. However, only a few produced IFN-γ. Both IFN-γ-producing and non-IFN-γ-producing HIV-specific CD8+ T cells were detected in the early stage (week (W)1 and W2 postimmunization (PI)), in the prolonged intermediate period of minimal response (W4-W26 PI), and in the final late phase of increased response (W30-W63 PI). Our longitudinal characterization showed that both subsets of cells underwent expansion, contraction, and memory generation/maintenance phases throughout the lifespan of the animal. Altogether, these findings bring insight to the heterogeneity of the immune T cell response induced by a single immunization with this DNA and strengthen the concept that used of the IFN-γ-ELISPOT assay alone may be insufficient to detect critical T cell responses to candidate HIV vaccines.

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Immune Responses following Neonatal DNA Vaccination Are Long-Lived, Abundant, and Qualitatively Similar to Those Induced by Conventional Immunization

Cited by 78 publications

References 46 publications

HER2 peptide-specific CD8+ T cells are proportionally detectable long after multiple DNA vaccinations

HER2 peptide-specific CD8+ T cells are proportionally detectable long after multiple DNA vaccinations

Direct Ex Vivo Kinetic and Phenotypic Analyses of CD8⁺T-Cell Responses Induced by DNA Immunization

Phenotypic and Functional Analysis of Immune CD8+ T Cell Responses Induced by a Single Injection of a HIV DNA Vaccine in Mice

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Immune Responses following Neonatal DNA Vaccination Are Long-Lived, Abundant, and Qualitatively Similar to Those Induced by Conventional Immunization

Cited by 78 publications

References 46 publications

HER2 peptide-specific CD8+ T cells are proportionally detectable long after multiple DNA vaccinations

HER2 peptide-specific CD8+ T cells are proportionally detectable long after multiple DNA vaccinations

Direct Ex Vivo Kinetic and Phenotypic Analyses of CD8+T-Cell Responses Induced by DNA Immunization

Phenotypic and Functional Analysis of Immune CD8+ T Cell Responses Induced by a Single Injection of a HIV DNA Vaccine in Mice

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Direct Ex Vivo Kinetic and Phenotypic Analyses of CD8⁺T-Cell Responses Induced by DNA Immunization