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T cell mediated immunity induced by the live-attenuated Shigella flexneri 2a vaccine candidate CVD 1208S in humans

Overview of attention for article published in Journal of Translational Medicine, March 2018
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Title
T cell mediated immunity induced by the live-attenuated Shigella flexneri 2a vaccine candidate CVD 1208S in humans
Published in
Journal of Translational Medicine, March 2018
DOI 10.1186/s12967-018-1439-1
Pubmed ID
Authors

Franklin R. Toapanta, Paula J. Bernal, Karen L. Kotloff, Myron M. Levine, Marcelo B. Sztein

Abstract

Shigellosis persists as a public health problem worldwide causing ~ 165,000 deaths every year, of which ~ 55,000 are in children less than 5 years of age. No vaccine against shigellosis is currently licensed. The live-attenuated Shigella flexneri 2a vaccine candidate CVD 1208S (S. flexneri 2a; ΔguaBA, Δset, Δsen) demonstrated to be safe and immunogenic in phase 1 and 2 clinical trials. Earlier reports focused on humoral immunity. However, Shigella is an intracellular pathogen and therefore, T cell mediated immunity (T-CMI) is also expected to play an important role. T-CMI responses after CVD 1208S immunization are the focus of the current study. Consenting volunteers were immunized orally (3 doses, 108 CFU/dose, 28 days apart) with CVD 1208S. T-CMI to IpaB was assessed using autologous EBV-transformed B-Lymphocytic cell lines as stimulator cells. T-CMI was assessed by the production of 4 cytokines (IFN-γ, IL-2, IL-17A and TNF-α) and/or expression of the degranulation marker CD107a in 14 volunteers (11 vaccine and 3 placebo recipients). Following the first immunization, T-CMI was detected in CD8 and CD4 T cells obtained from CVD 1208S recipients. Among CD8 T cells, the T effector memory (TEM) and central memory (TCM) subsets were the main cytokine/CD107a producers/expressors. Multifunctional (MF) cells were also detected in CD8 TEM cells. Cells with 2 and 3 functions were the most abundant. Interestingly, TNF-α appeared to be dominant in CD8 TEM MF cells. In CD4 T cells, TEM responses predominated. Following subsequent immunizations, no booster effect was detected. However, production of cytokines/expression of CD107a was detected in individuals who had previously not responded. After three doses, production of at least one cytokine/CD107a was detected in 8 vaccinees (73%) in CD8 TEM cells and in 10 vaccinees (90%) in CD4 TEM cells. CVD 1208S induces diverse T-CMI responses, which likely complement the humoral responses in protection from disease. Trial registration This study was approved by the Institutional Review Board and registered on ClinicalTrials.gov (identifier NCT01531530).

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 31 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 6 19%
Other 4 13%
Student > Ph. D. Student 4 13%
Student > Master 3 10%
Student > Doctoral Student 2 6%
Other 4 13%
Unknown 8 26%
Readers by discipline Count As %
Immunology and Microbiology 6 19%
Agricultural and Biological Sciences 4 13%
Medicine and Dentistry 4 13%
Psychology 3 10%
Pharmacology, Toxicology and Pharmaceutical Science 2 6%
Other 5 16%
Unknown 7 23%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 July 2019.
All research outputs
#12,251,193
of 15,418,020 outputs
Outputs from Journal of Translational Medicine
#2,352
of 2,902 outputs
Outputs of similar age
#209,904
of 279,832 outputs
Outputs of similar age from Journal of Translational Medicine
#1
of 2 outputs
Altmetric has tracked 15,418,020 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,902 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.0. This one is in the 10th percentile – i.e., 10% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 279,832 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 13th percentile – i.e., 13% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 2 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them