Evidence map›Paper›PMID 25020048›Full record

ArticleBioconjugate chemistry2014

Design of lipid nanocapsule delivery vehicles for multivalent display of recombinant Env trimers in HIV vaccination.

Sharmila Pejawar-Gaddy, James M Kovacs, Dan H Barouch, Bing Chen, Darrell J Irvine

Abstract read
In one paragraph

Article in Bioconjugate chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
–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. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Crosslinked polymer nanocapsules for therapeutic, diagnostic, and theranostic applications.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2020
    Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Bionanotechnology for vaccine design.Current opinion in biotechnology · 2018
    Review
  19. Article
  20. 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

5 authors.

Sharmila Pejawar-GaddyDepartment of Biological Engineering, #Koch Institute for Integrative Cancer Research, and ¶Department of Material Science, Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
James M Kovacs
Dan H Barouch
Bing Chen
Darrell J Irvine

Funding

Vaccine Adjuvant/ Delivery Systems CoreP01AI104715 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI ALLEN, TODD M · 2013 to 2017
$12.3M
Engineered lipid vesicles as potent vaccine vectors for HIVR01AI095109 · NIAID · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI IRVINE, DARRELL J · 2011 to 2015
$1.6M
Howard Hughes Medical InstituteNIAID NIH HHS AI095109NIAID NIH HHS AI104715NIAID NIH HHS P01 AI104715NIAID NIH HHS R01 AI095109
6 · The paper itself

Abstract

Immunization strategies that elicit antibodies capable of neutralizing diverse virus strains will likely be an important part of a successful vaccine against HIV. However, strategies to promote robust humoral responses against the native intact HIV envelope trimer structure are lacking. We recently developed chemically cross-linked lipid nanocapsules as carriers of molecular adjuvants and encapsulated or surface-displayed antigens, which promoted follicular helper T-cell responses and elicited high-avidity, durable antibody responses to a candidate malaria antigen. To apply this system to the delivery of HIV antigens, Env gp140 trimers with terminal his-tags (gp140T-his) were anchored to the surface of lipid nanocapsules via Ni-NTA-functionalized lipids. Initial experiments revealed that the large (409 kDa), heavily glycosylated trimers were capable of extracting fluid phase lipids from the membranes of nanocapsules. Thus, liquid-ordered and/or gel-phase lipid compositions were required to stably anchor trimers to the particle membranes. Trimer-loaded nanocapsules combined with the clinically relevant adjuvant monophosphoryl lipid A primed high-titer antibody responses in mice at antigen doses ranging from 5 μg to as low as 100 ng, whereas titers dropped more than 50-fold over the same dose range when soluble trimer was mixed with a strong oil-in-water adjuvant comparator. Nanocapsule immunization also broadened the number of distinct epitopes on the HIV trimer recognized by the antibody response. These results suggest that nanocapsules displaying HIV trimers in an oriented, multivalent presentation can promote key aspects of the humoral response against Env immunogens.

Indexed as

Protein MultimerizationVaccinationAnimalsAntigens, ViralDrug Carriersenv Gene Products, Human Immunodeficiency VirusEpitopesHIVImmunity, HumoralLipidsMiceMolecular WeightNanocapsulesProtein Structure, QuaternaryRecombinant ProteinsAntigens, ViralDrug Carriersenv Gene Products, Human Immunodeficiency VirusEpitopesLipidsNanocapsulesRecombinant Proteins

Identifiers

PMID25020048
PMCPMC4140538

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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.