Evidence map›Paper›PMID 34174879›Full record

ArticleMalaria journal2021

Transient knockdown of Anopheles stephensi LRIM1 using RNAi increases Plasmodium falciparum sporozoite salivary gland infections.

Peter F Billingsley, Kasim I George, Abraham G Eappen, Robert A Harrell, Robert Alford, Tao Li, Sumana Chakravarty, B Kim Lee Sim, Stephen L Hoffman, David A O'Brochta

Open access · goldAbstract read
In one paragraph

Article in Malaria journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.7field-weighted citation impact, top 32% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
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  5. Novel systems to study vector-pathogen interactions in malaria.Frontiers in cellular and infection microbiology · 2023
    Review
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  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Peter F BillingsleySanaria Inc, Suite A209, 9800 Medical Center Drive, Rockville, MD, 20850, USA. pbillingsley@sanaria.com.ORCID http://orcid.org/0000-0003-1142-4813
Kasim I GeorgeInstitute for Bioscience and Biotechnology Research and Department of Entomology, University of Maryland, Gudelsky Drive, Rockville, MD, 20850, USA.
Abraham G EappenSanaria Inc, Suite A209, 9800 Medical Center Drive, Rockville, MD, 20850, USA.
Robert A HarrellInstitute for Bioscience and Biotechnology Research and Department of Entomology, University of Maryland, Gudelsky Drive, Rockville, MD, 20850, USA.
Robert AlfordInstitute for Bioscience and Biotechnology Research and Department of Entomology, University of Maryland, Gudelsky Drive, Rockville, MD, 20850, USA.
Tao LiSanaria Inc, Suite A209, 9800 Medical Center Drive, Rockville, MD, 20850, USA.
Sumana ChakravartySanaria Inc, Suite A209, 9800 Medical Center Drive, Rockville, MD, 20850, USA.
B Kim Lee SimSanaria Inc, Suite A209, 9800 Medical Center Drive, Rockville, MD, 20850, USA.
Stephen L HoffmanSanaria Inc, Suite A209, 9800 Medical Center Drive, Rockville, MD, 20850, USA.
David A O'BrochtaInstitute for Bioscience and Biotechnology Research and Department of Entomology, University of Maryland, Gudelsky Drive, Rockville, MD, 20850, USA.
Sanaria · USAdvanced Bioscience Laboratories (United States) · USFoundation for the National Institutes of Health · US

Funding

Transgenic Mosquitoes for Improved Malaria Sporozoite Vaccine ManufactureR44AI077262 · NIAID · SANARIA, INC. · PI BILLINGSLEY, PETER F. · 2012 to 2014
$3.0M
NIAID NIH HHS R44 AI077262
6 · The paper itself

Abstract

backgroundPlasmodium falciparum (Pf) sporozoites (PfSPZ) can be administered as a highly protective vaccine conferring the highest protection seen to date. Sanaria® PfSPZ vaccines are produced using aseptically reared Anopheles stephensi mosquitoes. The bionomics of sporogonic development of P. falciparum in A. stephensi to fully mature salivary gland PfSPZ is thought to be modulated by several components of the mosquito innate immune system. In order to increase salivary gland PfSPZ infections in A. stephensi and thereby increase vaccine production efficiency, a gene knock down approach was used to investigate the activity of the immune deficiency (IMD) signaling pathway downstream effector leucine-rich repeat immune molecule 1 (LRIM1), an antagonist to Plasmodium development.

methodsExpression of LRIM1 in A. stephensi was reduced following injection of double stranded (ds) RNA into mosquitoes. By combining the Gal4/UAS bipartite system with in vivo expression of short hairpin (sh) RNA coding for LRIM1 reduced expression of LRIM1 was targeted in the midgut, fat body, and salivary glands. RT-qPCR was used to demonstrate fold-changes in gene expression in three transgenic crosses and the effects on P. falciparum infections determined in mosquitoes showing the greatest reduction in LRIM1 expression.

resultsLRIM1 expression could be reduced, but not completely silenced, by expression of LRIM1 dsRNA. Infections of P. falciparum oocysts and PfSPZ were consistently and significantly higher in transgenic mosquitoes than wild type controls, with increases in PfSPZ ranging from 2.5- to tenfold.

conclusionsPlasmodium falciparum infections in A. stephensi can be increased following reduced expression of LRIM1. These data provide the springboard for more precise knockout of LRIM1 for the eventual incorporation of immune-compromised A. stephensi into manufacturing of Sanaria's PfSPZ products.

Indexed as

RNA InterferenceAnimalsAnophelesFemaleGene Knockdown TechniquesInsect ProteinsPlasmodium falciparumSalivary GlandsSporozoitesInsect ProteinsLRIM1 protein, Anopheles gambiaeAnopheles stephensiGene silencingImmune systemMosquitoOocystPfSPZ vaccinePlasmodium falciparumSporozoite

Identifiers

PMID34174879
PMCPMC8235909
OpenAlexW3173698192

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.