CD8+ gamma-delta TCR+ and CD4+ T cells produce IFN-γ at 5–7 days after yellow fever vaccination in Indian rhesus macaques, before the induction of classical antigen-specific T cell responses

Neves, Patrícia; Rudersdorf, Richard; Galler, Ricardo; Bonaldo, Myrna C.; Santana, Marlon G. Veloso de; Mudd, Philip A.; Martins, Maurício A.; Rakasz, Eva G.; Wilson, Nancy A.; Watkins, David I.

doi:10.1016/j.vaccine.2010.09.090

Cited by 32 publications

(29 citation statements)

References 21 publications

(35 reference statements)

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“…In a comparison of 17DD and 17D-213 substrains in a pediatric cohort, the cytokine responses of the vaccines were similar, however revealing an enhanced inflammatory component for the group receiving the 17D-213 substrain vaccine [95]. IFN-gamma responses are observed to correlate with humoral, CD4+, and CD8+ responses [96, 97]. It is hoped that, by interrogation of specific immune response elements, predictive models of response to live-attenuated vaccines could be constructed, and in such a manner offer personalized insight to the safety and eventual protection available to the recipient.…”

Section: New Insights To Immunogenicity and Durability Of Protection mentioning

confidence: 99%

Current status and future prospects of yellow fever vaccines

Beck

Barrett²

2015

Expert Review of Vaccines

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Summary Yellow fever 17D vaccine is one of the oldest live-attenuated vaccines in current use that is recognized for historically immunogenic and safe properties. These unique properties of 17D are presently exploited in rationally designed recombinant vaccines targeting not only flaviviral antigens but also other pathogens of public health concern. Several candidate vaccines based on 17D have advanced to human trials, and a chimeric recombinant Japanese encephalitis vaccine utilizing the 17D backbone has been licensed. The mechanism(s) of attenuation for 17D are poorly understood; however, recent insights from large in silico studies have indicated particular host genetic determinants contributing to the immune response to the vaccine, which presumably influences the considerable durability of protection, now in many cases considered to be life-long. The very rare occurrence of severe adverse events for 17D is discussed, including a recent fatal case of vaccine-associated viscerotropic disease.

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Section: New Insights To Immunogenicity and Durability Of Protection mentioning

confidence: 99%

Current status and future prospects of yellow fever vaccines

Beck

Barrett²

2015

Expert Review of Vaccines

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“…The activation of innate immunity cell types, such as NK and gamma-delta T cells, results in the early production of gamma interferon in man, monkeys, and mice which may be of importance to the overall adaptive immune response. [15][16][17] The activation and maturation of different subsets of DCs is likely to contribute to the marked adaptive immune response after vaccination with the YF17D virus. 18 Analyzing microarrays on PBMCs of vaccinated humans, the most frequently activated gene was EIF2AK4 (GCN2) which is known to be related to the formation of stress granules.…”

Section: Immunological Aspects Of Vaccination With the Yellow Fever 1mentioning

confidence: 99%

The yellow fever 17D virus as a platform for new live attenuated vaccines

Bonaldo

Sequeira

Galler³

2014

Human Vaccines & Immunotherapeutics

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“…A potential caveat in this analysis relates to the sensitivity of our IFN-γ ELISPOT assay, which might have been reduced since PBMC from these animals produced high background levels of IFN-γ at days 14 and 17 post vaccination. We have recently described this phenomenon, which occurs after YF17D vaccination of rhesus macaques and appears to be caused by the activation of CD8 + γδ + and CD4 + T-cells [53]. Since this “spontaneous” production of IFN-γ increased the background of our ELISPOT assays during the first few weeks after vaccination, we likely missed low-frequency SIV-specific T-cell responses induced by the rYF17D/SIV vectors.…”

Section: Discussionmentioning

confidence: 89%

“…As a result, we may have missed low-frequency T-cell responses induced by rYF17D/SIV vaccination since this “spontaneous” production of IFN-γ increased the background of our IFN-γ ELISPOT assays. We have recently described this phenomenon in Indian rhesus macaques immunized with YF17D and found that it is mediated, at least in part, by activated CD8 + γδ + and CD4 + T-cells [53].…”

Section: Resultsmentioning

confidence: 98%

Immunogenicity of Seven New Recombinant Yellow Fever Viruses 17D Expressing Fragments of SIVmac239 Gag, Nef, and Vif in Indian Rhesus Macaques

et al. 2013

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An effective vaccine remains the best solution to stop the spread of human immunodeficiency virus (HIV). Cellular immune responses have been repeatedly associated with control of viral replication and thus may be an important element of the immune response that must be evoked by an efficacious vaccine. Recombinant viral vectors can induce potent T-cell responses. Although several viral vectors have been developed to deliver HIV genes, only a few have been advanced for clinical trials. The live-attenuated yellow fever vaccine virus 17D (YF17D) has many properties that make it an attractive vector for AIDS vaccine regimens. YF17D is well tolerated in humans and vaccination induces robust T-cell responses that persist for years. Additionally, methods to manipulate the YF17D genome have been established, enabling the generation of recombinant (r)YF17D vectors carrying genes from unrelated pathogens. Here, we report the generation of seven new rYF17D viruses expressing fragments of simian immunodeficiency virus (SIV)mac239 Gag, Nef, and Vif. Studies in Indian rhesus macaques demonstrated that these live-attenuated vectors replicated in vivo, but only elicited low levels of SIV-specific cellular responses. Boosting with recombinant Adenovirus type-5 (rAd5) vectors resulted in robust expansion of SIV-specific CD8+ T-cell responses, particularly those targeting Vif. Priming with rYF17D also increased the frequency of CD4+ cellular responses in rYF17D/rAd5-immunized macaques compared to animals that received rAd5 only. The effect of the rYF17D prime on the breadth of SIV-specific T-cell responses was limited and we also found evidence that some rYF17D vectors were more effective than others at priming SIV-specific T-cell responses. Together, our data suggest that YF17D – a clinically relevant vaccine vector – can be used to prime AIDS virus-specific T-cell responses in heterologous prime boost regimens. However, it will be important to optimize rYF17D-based vaccine regimens to ensure maximum delivery of all immunogens in a multivalent vaccine.

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CD8+ gamma-delta TCR+ and CD4+ T cells produce IFN-γ at 5–7 days after yellow fever vaccination in Indian rhesus macaques, before the induction of classical antigen-specific T cell responses

Cited by 32 publications

References 21 publications

Current status and future prospects of yellow fever vaccines

Current status and future prospects of yellow fever vaccines

The yellow fever 17D virus as a platform for new live attenuated vaccines

Immunogenicity of Seven New Recombinant Yellow Fever Viruses 17D Expressing Fragments of SIVmac239 Gag, Nef, and Vif in Indian Rhesus Macaques

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