Induction of Human T Cell–Mediated Immune Responses after Primary and Secondary Smallpox Vaccination

Kennedy, Jennifer; Frey, Sharon E.; Yan, Lihan; Rothman, Alan L.; Cruz, John; Newman, Frances K.; Orphin, Laura; Belshe, Robert B.; Ennis, Francis A.

doi:10.1086/423848

Cited by 76 publications

(65 citation statements)

References 29 publications

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“…Based on experience with other viruses, such as HIV (27,29), the WN virus E peptide-specific IFN-␥ responses may largely represent WNspecific CD8 ϩ T cells, although this was not specifically demonstrated. These results are consistent with studies of lymphocytic choriomeningitis virus in mice and vaccinia in humans demonstrating that effector CD8 ϩ T lymphocytes expand upon antigen stimulation and contract again after the acute phase of infection (30,31). The structural genes of divergent mosquito-borne flaviviruses such as WN and YF viruses have a lesser degree of homology (32).…”

Section: Discussionsupporting

confidence: 84%

A live, attenuated recombinant West Nile virus vaccine

Monath

Liu

Kanesa-thasan

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

208

119

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authors note that Fig. 5 did not include all vaccine study groups. The corrected figure and legend appear below. This error does not affect the conclusions of the article. Confidence intervals for Spearman's rank correlation of log 10 IFN-␥ producing PBMC per million and log10 stimulation index were based on Fisher's transformation. On day 14, the correlation was 0.491 (95% CI, 0.231-0.686); on day 28, the correlation was 0.188 (95% CI: Ϫ0.112 to 0.456).

show abstract

Section: Discussionsupporting

confidence: 84%

A live, attenuated recombinant West Nile virus vaccine

Monath

Liu

Kanesa-thasan

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

208

119

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“…Using whole viral Ag, CD4 ϩ cells up-regulating CD134 in response to vaccinia reached similar levels. IFN-␥ ϩ CD4 cells peaked at ϳ1%, as observed in this study and by others (18,61). To investigate the difference between assays, Zaunders et al sought, but did not detect, bystander CD4 T cell activation.…”

Section: Discussionsupporting

confidence: 62%

Dominance and Diversity in the Primary Human CD4 T Cell Response to Replication-Competent Vaccinia Virus

Jing¹,

Chong

Byrd³

et al. 2007

The Journal of Immunology

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Vaccination with replication-competent vaccinia protects against heterologous orthopoxvirus challenge. CD4 T cells have essential roles helping functionally important Ab and CD8 antiviral responses, and contribute to the durability of vaccinia-specific memory. Little is known about the specificity, diversity, or dominance hierarchy of orthopoxvirus-specific CD4 T cell responses. We interrogated vaccinia-reactive CD4 in vitro T cell lines with vaccinia protein fragments expressed from an unbiased genomic library, and also with a panel of membrane proteins. CD4 T cells from three primary vaccinees reacted with 44 separate antigenic regions in 35 vaccinia proteins, recognizing 8 to 20 proteins per person. The integrated responses to the Ags that we defined accounted for 49 to 81% of the CD4 reactivity to whole vaccinia Ag. Individual dominant Ags drove up to 30% of the total response. The gene F11L-encoded protein was immunodominant in two of three subjects and is fragmented in a replication-incompetent vaccine candidate. The presence of protein in virions was strongly associated with CD4 antigenicity. These findings are consistent with models in which exogenous Ag drives CD4 immunodominance, and provides tools to investigate the relationship between Ab and CD4 T cell specificity for complex pathogens.

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“…Serum and PBMC samples were collected at Study Weeks 0, 2,4,6,12,14,16,20,22,24,28,30,32,36 and 52 to measure antibody and CMI responses. All volunteers were recruited and enrolled in the Clinical Vaccine Research Unit, UMMS.…”

Section: 3b Study Design and Immunization Schedule-thismentioning

confidence: 99%

“…Wells containing media alone served as a negative control and wells containing 1 μg/ml phytohemagglutinin (PHA) served as a positive control. A CEF peptide pool containing defined epitopes of cytomegalovirus, Epstein-Barr virus and influenza A virus was used as a peptide positive control [30]. PBMC from HIV-1-infected donors and healthy control donors (with a known positive response to the CEF peptide pool) were included in each assay to assess reproducibility.…”

Section: Elispotmentioning

confidence: 99%

Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers

Wang

Kennedy

West

et al. 2008

Vaccine

124

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An optimally effective AIDS vaccine would likely require the induction of both neutralizing antibody and cell-mediated immune responses, which has proven difficult to obtain in previous clinical trials. Here we report the induction of Human Immunodeficiency Virus Type-1 (HIV-1)-specific immune responses in healthy adult volunteers that received the multi-gene, polyvalent, DNA prime-protein boost HIV-1 vaccine formulation, DP6−001 in a Phase I clinical trial conducted in healthy adult volunteers of both genders. Robust cross-subtype HIV-1-specific T cell responses were detected in IFNγ ELISPOT assays. Furthermore, we detected high titer serum antibody responses that recognized a wide range of primary HIV-1 Env antigens and also neutralized pseudotyped viruses that express the primary Env antigens from multiple HIV-1 subtypes. These findings demonstrate that the DNA prime-protein boost approach is an effective immunization method to elicit both humoral and cellmediated immune responses in humans, and that a polyvalent Env formulation could generate broad immune responses against HIV-1 viruses with diverse genetic backgrounds.

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Induction of Human T Cell–Mediated Immune Responses after Primary and Secondary Smallpox Vaccination

Cited by 76 publications

References 29 publications

A live, attenuated recombinant West Nile virus vaccine

A live, attenuated recombinant West Nile virus vaccine

Dominance and Diversity in the Primary Human CD4 T Cell Response to Replication-Competent Vaccinia Virus

Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers

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