Evidence map›Paper›PMID 22815152›Full record

ArticleClinical and vaccine immunology : CVI2012

Structural and immunological analysis of anthrax recombinant protective antigen adsorbed to aluminum hydroxide adjuvant.

Leslie Wagner, Anita Verma, Bruce D Meade, Karine Reiter, David L Narum, Rebecca A Brady, Stephen F Little, Drusilla L Burns

Abstract read
In one paragraph

Article in Clinical and vaccine immunology : CVI, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

25 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Human anthrax vaccines: Current status and future prospects.Human vaccines & immunotherapeutics · 2025
    Review
  3. Article
  4. Article
  5. Article
  6. Role of site-directed mutagenesis and adjuvants in the stability and potency of anthrax protective antigen.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022
    Review
  7. Designing StablePharmaceutics · 2022
    Article
  8. Article
  9. Two approaches for the stabilization ofHuman vaccines & immunotherapeutics · 2021
    Article
  10. Article
  11. Article
  12. Unraveling the enigma: elucidating the relationship between the physicochemical properties of aluminium-based adjuvants and their immunological mechanisms of action.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2018
    Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Development of a highly thermostable, adjuvanted human papillomavirus vaccine.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2015
    Article
  19. Article
  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

8 authors.

Leslie WagnerCenter for Biologics Evaluation and Research, Food and Drug Administration Bethesda, MD, USA.
Anita Verma
Bruce D Meade
Karine Reiter
David L Narum
Rebecca A Brady
Stephen F Little
Drusilla L Burns

Funding

Intramural NIH HHS
6 · The paper itself

Abstract

New anthrax vaccines currently under development are based on recombinant protective antigen (rPA) and formulated with aluminum adjuvant. Because long-term stability is a desired characteristic of these vaccines, an understanding of the effects of adsorption to aluminum adjuvants on the structure of rPA is important. Using both biophysical and immunological techniques, we compared the structure and immunogenicity of freshly prepared rPA-Alhydrogel formulations to that of formulations stored for 3 weeks at either room temperature or 37°C in order to assess the changes in rPA structure that might occur upon long-term storage on aluminum adjuvant. Intrinsic fluorescence emission spectra of tryptophan residues indicated that some tertiary structure alterations of rPA occurred during storage on Alhydrogel. Using anti-PA monoclonal antibodies to probe specific regions of the adsorbed rPA molecule, we found that two monoclonal antibodies that recognize epitopes located in domain 1 of PA exhibited greater reactivity to the stored formulations than to freshly prepared formulations. Immunogenicity of rPA-Alhydrogel formulations in mice was assessed by measuring the induction of toxin-neutralizing antibodies, as well as antibodies reactive to 12-mer peptides spanning the length of PA. Mice immunized with freshly prepared formulations developed significantly higher toxin-neutralizing antibody titers than mice immunized with the stored preparations. In contrast, sera from mice immunized with stored preparations exhibited increased reactivity to nine 12-mer peptides corresponding to sequences located throughout the rPA molecule. These results demonstrate that storage of rPA-Alhydrogel formulations can lead to structural alteration of the protein and loss of the ability to elicit toxin-neutralizing antibodies.

Indexed as

Adjuvants, ImmunologicAdsorptionAluminum HydroxideAnimalsAnthraxAnthrax VaccinesAntibodies, BacterialAntibodies, MonoclonalAntibodies, NeutralizingAntigens, BacterialAntitoxinsBacterial ToxinsDrug StorageFemaleMiceProtein ConformationAdjuvants, ImmunologicAluminum Hydroxideanthrax toxinAnthrax VaccinesAntibodies, BacterialAntibodies, MonoclonalAntibodies, NeutralizingAntigens, BacterialAntitoxinsBacterial Toxins

Identifiers

PMID22815152
PMCPMC3428410

What OpenQuestion holds

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Registered trials

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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.