Plasmid DNA initiates replication of yellow fever vaccine in vitro and elicits virus-specific immune response in mice

Correlates of immune-mediated protection to most viral and cancer vaccines are still unknown. This impedes the development of novel vaccines to incurable diseases such as HIV and cancer. In this study, we have used functional genomics and polychromatic flow cytometry to define the signature of the immune response to the yellow fever (YF) vaccine 17D (YF17D) in a cohort of 40 volunteers followed for up to 1 yr after vaccination. We show that immunization with YF17D leads to an integrated immune response that includes several effector arms of innate immunity, including complement, the inflammasome, and interferons, as well as adaptive immunity as shown by an early T cell response followed by a brisk and variable B cell response. Development of these responses is preceded, as demonstrated in three independent vaccination trials and in a novel in vitro system of primary immune responses (modular immune in vitro construct [MIMIC] system), by the coordinated up-regulation of transcripts for specific transcription factors, including STAT1, IRF7, and ETS2, which are upstream of the different effector arms of the immune response. These results clearly show that the immune response to a strong vaccine is preceded by coordinated induction of master transcription factors that lead to the development of a broad, polyfunctional, and persistent immune response that integrates all effector cells of the immune system.

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A qualitatively validated mathematical-computational model of the immune response to the yellow fever vaccine

BMC Immunology ◽

10.1186/s12865-018-0252-1 ◽

2018 ◽

Vol 19 (1) ◽

Cited By ~ 3

Author(s):

Carla R. B. Bonin ◽

Guilherme C. Fernandes ◽

Rodrigo W. dos Santos ◽

Marcelo Lobosco

Keyword(s):

Immune Response ◽

Computational Model ◽

Yellow Fever ◽

Yellow Fever Vaccine

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Randomized, double-blinded, controlled non-inferiority trials evaluating the immunogenicity and safety of fractional doses of Yellow Fever vaccines in Kenya and Uganda

Wellcome Open Research ◽

10.12688/wellcomeopenres.15579.1 ◽

2019 ◽

Vol 4 ◽

pp. 182 ◽

Cited By ~ 2

Author(s):

Derick Kimathi ◽

Aitana Juan ◽

Philip Bejon ◽

Rebecca F. Grais ◽

George M. Warimwe ◽

...

Keyword(s):

Immune Response ◽

Randomized Controlled Trials ◽

Yellow Fever ◽

Vaccine Dose ◽

World Health ◽

Yellow Fever Vaccine ◽

Controlled Trials ◽

Post Vaccination ◽

Randomized Controlled ◽

Link Type

Introduction: Yellow fever is endemic in specific regions of sub-Saharan Africa and the Americas, with recent epidemics occurring on both continents. The yellow fever vaccine is effective, affordable and safe, providing life-long immunity following a single dose vaccination. However, the vaccine production process is slow and cannot be readily scaled up during epidemics. This has led the World Health Organization (WHO) to recommend the use of fractional doses as a dose-sparing strategy during epidemics, but there are no randomized controlled trials of fractional yellow fever vaccine doses in Africa. Methods and analysis: We will recruit healthy adult volunteers, adults living with HIV, and children to a series of randomized controlled trials aiming to determine the immunogenicity and safety of fractional vaccine doses in comparison to the standard vaccine dose. The trials will be conducted across two sites; Kilifi, Kenya and Mbarara, Uganda. Recruited participants will be randomized to receive fractional or standard doses of yellow fever vaccine. Scheduled visits will include blood collection for serum and peripheral blood mononuclear cells (PBMCs) before vaccination and on various days – up to 2 years – post-vaccination. The primary outcome is the rate of seroconversion as measured by the plaque reduction neutralization test (PRNT50) at 28 days post-vaccination. Secondary outcomes include antibody titre changes, longevity of the immune response, safety assessment using clinical data, the nature and magnitude of the cellular immune response and post-vaccination control of viremia by vaccine dose. Ethics and dissemination: The clinical trial protocols have received approval from the relevant institutional ethics and regulatory review committees in Kenya and Uganda, and the WHO Ethics Review Committee. The research findings will be disseminated through open-access publications and presented at relevant conferences and workshops. Registration: ClinicalTrials.gov NCT02991495 (registered on 13 December 2016) and NCT04059471 (registered on 15 August 2019).

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Interference assessment of yellow fever vaccine with the immune response to a single-dose inactivated hepatitis A vaccine (1440 EL.U.). A controlled study in adults

Vaccine ◽

10.1016/0264-410x(96)00059-x ◽

1996 ◽

Vol 14 (11) ◽

pp. 1028-1030 ◽

Cited By ~ 21

Author(s):

A Gil

Keyword(s):

Immune Response ◽

Single Dose ◽

Yellow Fever ◽

Hepatitis A ◽

Yellow Fever Vaccine ◽

Controlled Study

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Tumor-Specific Immune Response: Current In Vitro Analyses May Not Reflect the In Vivo Immune Status

Critical Reviews™ in Immunology ◽

10.1615/critrevimmunol.v18.i1-2.90 ◽

1998 ◽

Vol 18 (1-2) ◽

pp. 77-86 ◽

Cited By ~ 28

Author(s):

Florence Faure ◽

Jos Even ◽

Philippe Kourilsky

Keyword(s):

Immune Response ◽

Immune Status ◽

Specific Immune Response ◽

Response Current ◽

Tumor Specific Immune Response

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Restricted replication and lysosomal trafficking of yellow fever 17D vaccine virus in human dendritic cells

Journal of General Virology ◽

10.1099/vir.0.82272-0 ◽

2007 ◽

Vol 88 (1) ◽

pp. 148-156 ◽

Cited By ~ 28

Author(s):

Dupeh R. Palmer ◽

Stefan Fernandez ◽

John Bisbing ◽

Kristina K. Peachman ◽

Mangala Rao ◽

...

Keyword(s):

Dendritic Cells ◽

Immune Responses ◽

Yellow Fever ◽

Virus Replication ◽

Yellow Fever Virus ◽

Vaccine Virus ◽

Yellow Fever Vaccine ◽

Effective Vaccine ◽

Contributing Factors

The yellow fever virus attenuated 17D vaccine strain is a safe and effective vaccine and a valuable model system for evaluating immune responses against attenuated viral variants. This study compared the in vitro interactions of the commercially available yellow fever vaccine (YF-VAX), Dengue virus and the live-attenuated dengue vaccine PDK50 with dendritic cells (DCs), the main antigen-presenting cells at the initiation of immune responses. Similar to PDK50, infection with YF-VAX generated activated DCs; however, for YF-VAX, activation occurred with limited intracellular virus replication. The majority of internalized virus co-localized with endolysosomal markers within 90 min, suggesting that YF-VAX is processed rapidly in DCs. These results indicate that restricted virus replication and lysosomal compartmentalization may be important contributing factors to the success of the YF-VAX vaccine.

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Yellow fever 17D as a vaccine vector for microbial CTL epitopes

Journal of Experimental Medicine ◽

10.1084/jem.20041526 ◽

2005 ◽

Vol 201 (2) ◽

pp. 201-209 ◽

Cited By ~ 49

Author(s):

Deng Tao ◽

Giovanna Barba-Spaeth ◽

Urvashi Rai ◽

Victor Nussenzweig ◽

Charles M. Rice ◽

...

Keyword(s):

T Cell ◽

Yellow Fever ◽

Cell Epitope ◽

Parasite Burden ◽

Plasmodium Yoelii ◽

Yellow Fever Vaccine ◽

T Cell Epitopes ◽

High Level

The yellow fever vaccine 17D (17D) is safe, and after a single immunizing dose, elicits long-lasting, perhaps lifelong protective immunity. One of the major challenges facing delivery of human vaccines in underdeveloped countries is the need for multiple injections to achieve full efficacy. To examine 17D as a vector for microbial T cell epitopes, we inserted the H-2Kd–restricted CTL epitope of the circumsporozoite protein (CS) of Plasmodium yoelii between 17D nonstructural proteins NS2B and NS3. The recombinant virus, 17D-Py, was replication competent and stable in vitro and in vivo. A single subcutaneous injection of 105 PFU diminished the parasite burden in the liver by ∼70%. The high level of protection lasted between 4 and 8 wk after immunization, but a significant effect was documented even 24 wk afterwards. Thus, the immunogenicity of a foreign T cell epitope inserted into 17D mimics some of the remarkable properties of the human vaccine. Priming with 17D-Py followed by boosting with irradiated sporozoites conferred sterile immunity to 90% of the mice. This finding indicates that the immune response of vaccine-primed individuals living in endemic areas could be sustained and magnified by the bite of infected mosquitoes.

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