Human Immune Memory to Yellow Fever and Smallpox Vaccination

Wrammert, Jens; Miller, Joe; Akondy, Rama; Ahmed, Rafi

doi:10.1007/s10875-008-9267-3

Cited by 31 publications

(26 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[27][28][29][30] In the present study, CD8 + and CD4 + T cell responses and the cytokine responses were similar in the Ig and saline recipients. Ki-67 is up-regulated in recently divided or cycling cells.…”

Section: Discussionsupporting

confidence: 64%

“…Bcl-2 down-regulation indicates susceptibility to apoptosis, which is also a characteristic of T cells differentiating to become effectors. 20,30 HLA-DR and CD38 are expressed by activated CD8 + and CD4 + T cells during acute viral infections in humans. 20,29,30 In our study, 3-4% of total CD8 + T cells were activated (determined by Ki-67 + / Bcl-2 low and HLA-DR + /CD38 + markers) at day 14, confirming our earlier work.…”

Section: Discussionmentioning

confidence: 99%

“…20,30 HLA-DR and CD38 are expressed by activated CD8 + and CD4 + T cells during acute viral infections in humans. 20,29,30 In our study, 3-4% of total CD8 + T cells were activated (determined by Ki-67 + / Bcl-2 low and HLA-DR + /CD38 + markers) at day 14, confirming our earlier work. 20 A single outlier value that we observed + T cells (19%) in one participant likely represents an intercurrent infection unrelated to the study, because this activated phenotype may be seen with any acute infection (Figure 4).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

A Randomized, Double-Blind, Controlled Trial of the 17D Yellow Fever Virus Vaccine Given in Combination with Immune Globulin or Placebo: Comparative Viremia and Immunogenicity

Edupuganti

Eidex²,

Keyserling

et al. 2013

The American Journal of Tropical Medicine and Hygiene

Self Cite

View full text Add to dashboard Cite

Abstract. We evaluated whether coadministration of the yellow fever (YF) virus vaccine with human immunoglobulin (Ig) that contained YF virus-neutralizing antibodies would reduce post-vaccination viremia without compromising immunogenicity and thus, potentially mitigate YF vaccine-associated adverse events. We randomized 80 participants to receive either YF vaccine and Ig or YF vaccine and saline placebo. Participants were followed for 91 days for safety and assessments of viremia and immunogenicity. There were no differences found between the two groups in the proportion of vaccinated participants who developed viremia, seroconversion, cluster of differentiation (CD)-8 + and CD4 + T-cell responses, and cytokine responses. These results argue against one putative explanation for the increased reporting of YF vaccine side effects in recent years (i.e., a change in travel clinic practice after 1996 when hepatitis A prophylaxis with vaccine replaced routine use of pre-travel Ig, thus potentially removing an incidental YF vaccineattenuating effect of anti-YF virus antibodies present in Ig) (ClinicalTrials.gov identifier: NCT00254826).

show abstract

Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A Randomized, Double-Blind, Controlled Trial of the 17D Yellow Fever Virus Vaccine Given in Combination with Immune Globulin or Placebo: Comparative Viremia and Immunogenicity

Edupuganti

Eidex²,

Keyserling

et al. 2013

The American Journal of Tropical Medicine and Hygiene

Self Cite

View full text Add to dashboard Cite

show abstract

“…While neutralizing antibody responses to viral structural proteins are considered to be the predominant protective effect elicited by vaccination, limited published data imply that T cell help may play some role in promoting protection (24,25). Activated CD4 ϩ T cells have been shown to appear early after YF vaccination and are known to produce cytokines that support the activation and differentiation of B cells (26).…”

Section: Discussionmentioning

confidence: 99%

Yellow Fever Vaccination Elicits Broad Functional CD4 ⁺ T Cell Responses That Recognize Structural and Nonstructural Proteins

James

LaFond

Gates

et al. 2013

J Virol

View full text Add to dashboard Cite

bYellow fever virus (YFV) can induce acute, life-threatening disease that is a significant health burden in areas where yellow fever is endemic, but it is preventable through vaccination. The live attenuated 17D YFV strain induces responses characterized by neutralizing antibodies and strong T cell responses. This vaccine provides an excellent model for studying human immunity. While several studies have characterized YFV-specific antibody and CD8 ؉ T cell responses, less is known about YFV-specific CD4 ؉ T cells. Here we characterize the epitope specificity, functional attributes, and dynamics of YFV-specific T cell responses in vaccinated subjects by investigating peripheral blood mononuclear cells by using HLA-DR tetramers. A total of 112 epitopes restricted by seven common HLA-DRB1 alleles were identified. Epitopes were present within all YFV proteins, but the capsid, envelope, NS2a, and NS3 proteins had the highest epitope density. Antibody blocking demonstrated that the majority of YFV-specific T cells were HLA-DR restricted. Therefore, CD4؉ T cell responses could be effectively characterized with HLA-DR tetramers. Ex vivo tetramer analysis revealed that YFV-specific T cells persisted at frequencies ranging from 0 to 100 cells per million that are detectable years after vaccination. Longitudinal analysis indicated that YFV-specific CD4 ؉ T cells reached peak frequencies, often exceeding 250 cells per million, approximately 2 weeks after vaccination. As frequencies subsequently declined, YFV-specific cells regained CCR7 expression, indicating a shift from effector to central memory. Cells were typically CXCR3 positive, suggesting Th1 polarization, and produced gamma interferon and other cytokines after reactivation in vitro. Therefore, YFV elicits robust early effector CD4؉ T cell responses that contract, forming a detectable memory population. Members of the family Flaviviridae such as Yellow fever virus (YFV) are important causes of illness both historically and at present, causing a significant health burden in areas where yellow fever is endemic (1). Yellow fever (YF) produces symptoms ranging from a mild flu-like illness to hemorrhagic fever and organ failure, but infection is preventable through vaccination (2, 3). The YF vaccine uses a live attenuated virus (17D) and is safe and extremely effective, generating robust antibody responses that persist for decades (4, 5). The vaccine is known to elicit neutralizing antibodies and strong T cell responses in nearly all recipients (6, 7). Therefore, the YFV 17D vaccine is an excellent and important model for studying human antiviral immunity. Multiple studies have investigated the attributes and dynamics of CD4 ϩ and CD8 ϩ T cell responses following YF vaccination (8-12). By using a variety of readouts, these studies demonstrated that YFVspecific CD8 ϩ T cell responses are polyfunctional, exhibit distinct surface phenotypic markers, and peak approximately 2 to 4 weeks after vaccination. Blom et al. evaluated both CD4 ϩ and CD8 ϩ T cell responses by examinin...

show abstract

“…The most recent versions of smallpox vaccines are based on a live, replicating bovine pathogen (vaccinia virus) that confers protective immunity against disease caused by a related human pathogen (variola virus), and is safe for use in humans. The basis of protective immunity from live attenuated viral vaccines is now believed to be an induction of crossreactive antigen-specific antibody and T cell responses (Wrammert, Miller, Akondy, & Ahmed, 2009) as a result of limited viral infection launched by delivery of an intact viral genome. Today, there are several licensed live attenuated vaccines that function in a similar manner, including those that protect against viral (polio, measles, mumps, rubella, influenza, yellow fever, rotavirus, chicken pox) and bacterial diseases (tuberculosis, typhoid fever).…”

Section: History Of Nucleic Acid Vaccinesmentioning

confidence: 99%

Self-Amplifying mRNA Vaccines

Brito

Kommareddy

Maione

et al. 2015

Nonviral Vectors for Gene Therapy - Physical Methods and Medical Translation

139

160

View full text Add to dashboard Cite

Human Immune Memory to Yellow Fever and Smallpox Vaccination

Abstract: Here, we summarize the work of our laboratory and others on B and T cell responses and the establishment and maintenance of immune memory after acute viral infections induced by vaccination with two of the most successful vaccines to date, the yellow fever and the smallpox vaccines.

Cited by 31 publications

References 48 publications

A Randomized, Double-Blind, Controlled Trial of the 17D Yellow Fever Virus Vaccine Given in Combination with Immune Globulin or Placebo: Comparative Viremia and Immunogenicity

A Randomized, Double-Blind, Controlled Trial of the 17D Yellow Fever Virus Vaccine Given in Combination with Immune Globulin or Placebo: Comparative Viremia and Immunogenicity

Yellow Fever Vaccination Elicits Broad Functional CD4 ⁺ T Cell Responses That Recognize Structural and Nonstructural Proteins

Self-Amplifying mRNA Vaccines

Contact Info

Product

Resources

About

Human Immune Memory to Yellow Fever and Smallpox Vaccination

Abstract: Here, we summarize the work of our laboratory and others on B and T cell responses and the establishment and maintenance of immune memory after acute viral infections induced by vaccination with two of the most successful vaccines to date, the yellow fever and the smallpox vaccines.

Cited by 31 publications

References 48 publications

A Randomized, Double-Blind, Controlled Trial of the 17D Yellow Fever Virus Vaccine Given in Combination with Immune Globulin or Placebo: Comparative Viremia and Immunogenicity

A Randomized, Double-Blind, Controlled Trial of the 17D Yellow Fever Virus Vaccine Given in Combination with Immune Globulin or Placebo: Comparative Viremia and Immunogenicity

Yellow Fever Vaccination Elicits Broad Functional CD4 + T Cell Responses That Recognize Structural and Nonstructural Proteins

Self-Amplifying mRNA Vaccines

Contact Info

Product

Resources

About

Yellow Fever Vaccination Elicits Broad Functional CD4 ⁺ T Cell Responses That Recognize Structural and Nonstructural Proteins