Evidence map›Paper›PMID 20427625›Full record

ArticleClinical and vaccine immunology : CVI2010

Options for inactivation, adjuvant, and route of topical administration of a killed, unencapsulated pneumococcal whole-cell vaccine.

Ying-Jie Lu, Puja Yadav, John D Clements, Sophie Forte, Amit Srivastava, Claudette M Thompson, Robert Seid, Jee Look, Mark Alderson, Andrea Tate and 4 more

Open access · diamondAbstract readEvaluation Study
In one paragraph

Article in Clinical and vaccine immunology : CVI, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
5.5field-weighted citation impact, top 4% 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

59 citing papers in PubMed, 100 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Human vaccines & immunotherapeutics · 2025
    Review
  5. Article
  6. Article
  7. Novel processes to obtain pneumococcal surface proteins for vaccines.Applied microbiology and biotechnology · 2025
    Review
  8. A CRISPRi library screen in group BInfection and immunity · 2025
    Article
  9. A CRISPRi Library Screen in Group BbioRxiv : the preprint server for biology · 2024
    Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Current Progress and Challenges in the Study of Adjuvants for Oral Vaccines.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023
    Review
  15. Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. 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

14 authors at 4 institutions in 1 country.

Ying-Jie LuDivision of Infectious Diseases, Children's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
Puja Yadav
John D Clements
Sophie Forte
Amit Srivastava
Claudette M Thompson
Robert Seid
Jee Look
Mark Alderson
Andrea Tate
Jean-François Maisonneuve
George Robertson
Porter W Anderson
Richard Malley
Harvard University · USTulane University · USBoston Children's Hospital · USProgram for Appropriate Technology in Health · US

Funding

INFECTIOUS DISEASE AND BASIC MICROBIOLOGICAL MECHANISMST32AI007061 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Marcia B Goldberg · 1985 to 2026
$12.1M
Pneumococcal immunization through a novel mechanismR01AI067737 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI MALLEY, RICHARD · 2006 to 2010
$2.0M
Pneumolysin, Innate and Acquired Immunity to PneumococciK08AI051526 · NIAID · CHILDREN'S HOSPITAL BOSTON · PI MALLEY, RICHARD · 2002 to 2005
$503k
NIAID NIH HHS AI067737-01NIAID NIH HHS AI51526-01NIAID NIH HHS K08 AI051526NIAID NIH HHS R01 AI067737NIAID NIH HHS T32 AI007061
6 · The paper itself

Abstract

We previously reported that ethanol-killed cells of a noncapsulated strain of Streptococcus pneumoniae, given intranasally with cholera toxin as an adjuvant, protect rats against pneumonia and mice against colonization of the nasopharynx and middle ear by capsulated pneumococci of various serotypes. The acceleration of pneumococcal clearance from the nasopharynx in mice is CD4+ T cell-dependent and interleukin 17A (IL-17A) mediated and can be antibody independent. Here, anticipating human studies, we have demonstrated protection with a new vaccine strain expressing a nonhemolytic derivative of pneumolysin and grown in bovine-free culture medium. Killing the cells with chloroform, trichloroethylene, or beta-propiolactone--all used without postinactivation washing--produced more-potent immunogens than ethanol, and retention of soluble components released from the cells contributed to protection. Two sequential intranasal administrations of as little as 1 microg of protein (total of cellular and soluble combined) protected mice against nasopharyngeal challenge with pneumococci. Nontoxic single and double mutants of Escherichia coli heat-labile toxin were effective as mucosal adjuvants. Protection was induced by the sublingual and buccal routes, albeit requiring larger doses than when given intranasally. Protection was likewise induced transdermally with sonicates of the killed-cell preparation. Thus, this whole-cell antigen can be made and administered in a variety of ways to suit the manufacturer and the vaccination program and is potentially a solution to the need for a low-cost vaccine to reduce the burden of childhood pneumococcal disease in low-income countries.

Indexed as

Pneumococcal VaccinesStreptolysinsVaccines, InactivatedAdjuvants, ImmunologicAdministration, BuccalAdministration, IntranasalAdministration, SublingualAnimalsBacterial ProteinsBacterial ToxinsCholera ToxinEnterotoxinsEscherichia coli ProteinsHumansMiceMice, Inbred C57BLAdjuvants, ImmunologicBacterial ProteinsBacterial ToxinsCholera ToxinEnterotoxinsEscherichia coli Proteinsheat-labile enterotoxin, E coliplY protein, Streptococcus pneumoniaePneumococcal VaccinesStreptolysinsVaccines, Inactivated

Identifiers

PMID20427625
PMCPMC2884428
OpenAlexW2130103410

What OpenQuestion holds

Textmetadata
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.