Evidence map›Paper›PMID 35087099›Full record

ArticleNPJ vaccines2022

Restricted valency (NPNA)

Mark D Langowski, Farhat A Khan, Sofya Savransky, Dallas R Brown, Arasu Balasubramaniyam, William B Harrison, Xiaoyan Zou, Zoltan Beck, Gary R Matyas, Jason A Regules and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ vaccines, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
4.0field-weighted citation impact, top 6% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
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  7. Review
  8. Review
  9. Article
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  12. Article
  13. A multivalentBioengineering & translational medicine · 2023
    Article
  14. Article
  15. Article
  16. Humoral Immune Responses toInfection and drug resistance · 2023
    Review
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

14 authors at 4 institutions in 1 country.

Mark D Langowski *Structural Vaccinology Lab, Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Farhat A Khan *Structural Vaccinology Lab, Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Sofya SavranskyStructural Vaccinology Lab, Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Dallas R BrownStructural Vaccinology Lab, Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Arasu BalasubramaniyamStructural Vaccinology Lab, Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
William B HarrisonStructural Vaccinology Lab, Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Xiaoyan ZouMalaria Department, Naval Medical Research Center, Silver Spring, MD, USA.
Zoltan BeckUS Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Gary R MatyasUS Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.ORCID http://orcid.org/0000-0002-2074-2373
Jason A RegulesMalaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Robin MillerUnited States Agency for International Development, Washington, DC, USA.
Lorraine A SoissonUnited States Agency for International Development, Washington, DC, USA.
Adrian H BatchelorStructural Vaccinology Lab, Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Sheetij DuttaStructural Vaccinology Lab, Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA. sheetij.dutta.civ@mail.mil.ORCID http://orcid.org/0000-0002-4571-1880
Walter Reed Army Institute of Research · USUnited States Agency for International Development · USNaval Medical Research Command · USPfizer (United States) · US

Funding

Predoctoral Training in Pharmacological Sciences (Resubmission)T32GM133332 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Tija C. Jacob, Francisco Jose Schopfer · 2020 to 2026
$1.8M
NIGMS NIH HHS T32 GM133332
6 · The paper itself

Abstract

The Circumsporozoite Protein (CSP) of Plasmodium falciparum contains an N-terminal region, a conserved Region I (RI), a junctional region, 25-42 copies of major (NPNA) and minor repeats followed by a C-terminal domain. The recently approved malaria vaccine, RTS,S/AS01 contains NPNAx19 and the C-terminal region of CSP. The efficacy of RTS,S against natural infection is low and short-lived, and mapping epitopes of inhibitory monoclonal antibodies may allow for rational improvement of CSP vaccines. Tobacco Mosaic Virus (TMV) was used here to display the junctional epitope (mAb CIS43), Region I (mAb 5D5), NPNAx5, and NPNAx20 epitope of CSP (mAbs 317 and 580). Protection studies in mice revealed that Region I did not elicit protective antibodies, and polyclonal antibodies against the junctional epitope showed equivalent protection to NPNAx5. Combining the junctional and NPNAx5 epitopes reduced immunogenicity and efficacy, and increasing the repeat valency to NPNAx20 did not improve upon NPNAx5. TMV was confirmed as a versatile vaccine platform for displaying small epitopes defined by neutralizing mAbs. We show that polyclonal antibodies against engineered VLPs can recapitulate the binding specificity of the mAbs and immune-focusing by reducing the structural complexity of an epitope may be superior to immune-broadening as a vaccine design approach. Most importantly the junctional and restricted valency NPNA epitopes can be the basis for developing highly effective second-generation malaria vaccine candidates.

Identifiers

PMID35087099
PMCPMC8795123
OpenAlexW4210620255

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.