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Modest heterologous protection after Plasmodium falciparum sporozoite immunization: a double-blind randomized controlled clinical trial

Overview of attention for article published in BMC Medicine, September 2017
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3 tweeters
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1 Redditor

Citations

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56 Mendeley
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Title
Modest heterologous protection after Plasmodium falciparum sporozoite immunization: a double-blind randomized controlled clinical trial
Published in
BMC Medicine, September 2017
DOI 10.1186/s12916-017-0923-4
Pubmed ID
Authors

Jona Walk, Isaie J. Reuling, Marije C. Behet, Lisette Meerstein-Kessel, Wouter Graumans, Geert-Jan van Gemert, Rianne Siebelink-Stoter, Marga van de Vegte-Bolmer, Thorsten Janssen, Karina Teelen, Johannes H. W. de Wilt, Quirijn de Mast, André J. van der Ven, Ernest Diez Benavente, Susana Campino, Taane G. Clark, Martijn A. Huynen, Cornelus C. Hermsen, Else M. Bijker, Anja Scholzen, Robert W. Sauerwein

Abstract

A highly efficacious vaccine is needed for malaria control and eradication. Immunization with Plasmodium falciparum NF54 parasites under chemoprophylaxis (chemoprophylaxis and sporozoite (CPS)-immunization) induces the most efficient long-lasting protection against a homologous parasite. However, parasite genetic diversity is a major hurdle for protection against heterologous strains. We conducted a double-blind, randomized controlled trial in 39 healthy participants of NF54-CPS immunization by bites of 45 NF54-infected (n = 24 volunteers) or uninfected mosquitoes (placebo; n = 15 volunteers) against a controlled human malaria infection with the homologous NF54 or the genetically distinct NF135.C10 and NF166.C8 clones. Cellular and humoral immune assays were performed as well as genetic characterization of the parasite clones. NF54-CPS immunization induced complete protection in 5/5 volunteers against NF54 challenge infection at 14 weeks post-immunization, but sterilely protected only 2/10 and 1/9 volunteers against NF135.C10 and NF166.C8 challenge infection, respectively. Post-immunization plasma showed a significantly lower capacity to block heterologous parasite development in primary human hepatocytes compared to NF54. Whole genome sequencing showed that NF135.C10 and NF166.C8 have amino acid changes in multiple antigens targeted by CPS-induced antibodies. Volunteers protected against heterologous challenge were among the stronger immune responders to in vitro parasite stimulation. Although highly protective against homologous parasites, NF54-CPS-induced immunity is less effective against heterologous parasite clones both in vivo and in vitro. Our data indicate that whole sporozoite-based vaccine approaches require more potent immune responses for heterologous protection. This trial is registered in clinicaltrials.gov, under identifier NCT02098590 .

Twitter Demographics

The data shown below were collected from the profiles of 3 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 56 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 56 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 12 21%
Student > Ph. D. Student 10 18%
Student > Bachelor 6 11%
Student > Master 6 11%
Other 4 7%
Other 10 18%
Unknown 8 14%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 10 18%
Immunology and Microbiology 9 16%
Medicine and Dentistry 8 14%
Agricultural and Biological Sciences 7 13%
Nursing and Health Professions 2 4%
Other 4 7%
Unknown 16 29%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 15 September 2017.
All research outputs
#6,742,205
of 11,771,184 outputs
Outputs from BMC Medicine
#1,627
of 1,884 outputs
Outputs of similar age
#127,641
of 265,077 outputs
Outputs of similar age from BMC Medicine
#29
of 39 outputs
Altmetric has tracked 11,771,184 research outputs across all sources so far. This one is in the 40th percentile – i.e., 40% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,884 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 33.3. This one is in the 12th percentile – i.e., 12% 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 265,077 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 39 others from the same source and published within six weeks on either side of this one. This one is in the 20th percentile – i.e., 20% of its contemporaries scored the same or lower than it.