Evidence map›Paper›PMID 34707606›Full record

ArticleFrontiers in immunology2021

Alternative Complement Pathway Inhibition Abrogates Pneumococcal Opsonophagocytosis in Vaccine-Naïve, but Not in Vaccinated Individuals.

Lukas Muri, Emma Ispasanie, Anna Schubart, Christine Thorburn, Natasa Zamurovic, Thomas Holbro, Michael Kammüller, Gerd Pluschke

Open access · goldAbstract readComparative Study
In one paragraph

Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

15 citing papers in PubMed, 22 citations in OpenAlex.

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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

8 authors at 3 institutions in 2 countries.

Lukas MuriMolecular Immunology Unit, Swiss Tropical and Public Health Institute, Basel, Switzerland.
Emma IspasanieMolecular Immunology Unit, Swiss Tropical and Public Health Institute, Basel, Switzerland.
Anna SchubartTranslational Medicine-Preclinical Safety, Novartis Institutes for Biomedical Research, Basel, Switzerland.
Christine ThorburnNovartis Pharma AG, Global Drug Development, London, United Kingdom.
Natasa ZamurovicTranslational Medicine-Preclinical Safety, Novartis Institutes for Biomedical Research, Basel, Switzerland.
Thomas HolbroNovartis Pharma AG, Global Drug Development, Basel, Switzerland.
Michael KammüllerTranslational Medicine-Preclinical Safety, Novartis Institutes for Biomedical Research, Basel, Switzerland.
Gerd PluschkeMolecular Immunology Unit, Swiss Tropical and Public Health Institute, Basel, Switzerland.
Novartis (Switzerland) · CHSwiss Tropical and Public Health Institute · CHNovartis (United Kingdom) · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

To assess the relative contribution of opsonisation by antibodies, classical and alternative complement pathways to pneumococcal phagocytosis, we analyzed killing of pneumococci by human blood leukocytes collected from vaccine-naïve and PCV13-vaccinated subjects. With serotype 4 pneumococci as model, two different physiologic opsonophagocytosis assays based on either hirudin-anticoagulated whole blood or on washed cells from EDTA-anticoagulated blood reconstituted with active serum, were compared. Pneumococcal killing was measured in the presence of inhibitors targeting the complement components C3, C5, MASP-2, factor B or factor D. The two assay formats yielded highly consistent and comparable results. They highlighted the importance of alternative complement pathway activation for efficient opsonophagocytic killing in blood of vaccine-naïve subjects. In contrast, alternative complement pathway inhibition did not affect pneumococcal killing in PCV13-vaccinated individuals. Independent of amplification by the alternative pathway, even low capsule-specific antibody concentrations were sufficient to efficiently trigger classical pathway mediated opsonophagocytosis. In heat-inactivated or C3-inhibited serum, high concentrations of capsule-specific antibodies were required to trigger complement-independent opsonophagocytosis. Our findings suggest that treatment with alternative complement pathway inhibitors will increase susceptibility for invasive pneumococcal infection in non-immune subjects, but it will not impede pneumococcal clearance in vaccinated individuals.

Indexed as

Complement Pathway, AlternativeOpsonizationVaccinationAdultAgedComplement Inactivator ProteinsComplement System ProteinsFemaleHost-Pathogen InteractionsHumansLongitudinal StudiesMaleMiddle AgedPneumococcal InfectionsPneumococcal VaccinesStreptococcus pneumoniae13-valent pneumococcal vaccineComplement Inactivator ProteinsComplement System ProteinsPneumococcal Vaccinesalternative pathway inhibitorcomplement systeminnate immunitymicrobial immunologyopsonophagocytosisStreptococcus pneumoniae

Identifiers

PMID34707606
PMCPMC8543009
OpenAlexW3205318374

What OpenQuestion holds

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LicenceCC BY
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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.