Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

A vaccine combination of lipid nanoparticles and a cholera toxin adjuvant derivative greatly improves lung protection against influenza virus infection

Bernasconi, Valentina ; Norling, Karin ; Gribonika, Inta LU orcid ; Ong, Li Ching ; Burazerovic, Sabina ; Parveen, Nagma ; Schön, Karin ; Stensson, Anneli ; Bally, Marta and Larson, Göran , et al. (2021) In Mucosal Immunology 14(2). p.523-536
Abstract

This is a proof-of-principle study demonstrating that the combination of a cholera toxin derived adjuvant, CTA1-DD, and lipid nanoparticles (LNP) can significantly improve the immunogenicity and protective capacity of an intranasal vaccine. We explored the self-adjuvanted universal influenza vaccine candidate, CTA1-3M2e-DD (FPM2e), linked to LNPs. We found that the combined vector greatly enhanced survival against a highly virulent PR8 strain of influenza virus as compared to when mice were immunized with FPM2e alone. The combined vaccine vector enhanced early endosomal processing and peptide presentation in dendritic cells and upregulated co-stimulation. The augmenting effect was CTA1-enzyme dependent. Whereas systemic anti-M2e... (More)

This is a proof-of-principle study demonstrating that the combination of a cholera toxin derived adjuvant, CTA1-DD, and lipid nanoparticles (LNP) can significantly improve the immunogenicity and protective capacity of an intranasal vaccine. We explored the self-adjuvanted universal influenza vaccine candidate, CTA1-3M2e-DD (FPM2e), linked to LNPs. We found that the combined vector greatly enhanced survival against a highly virulent PR8 strain of influenza virus as compared to when mice were immunized with FPM2e alone. The combined vaccine vector enhanced early endosomal processing and peptide presentation in dendritic cells and upregulated co-stimulation. The augmenting effect was CTA1-enzyme dependent. Whereas systemic anti-M2e antibody and CD4+ T-cell responses were comparable to those of the soluble protein, the local respiratory tract IgA and the specific Th1 and Th17 responses were strongly enhanced. Surprisingly, the lung tissue did not exhibit gross pathology upon recovery from infection and M2e-specific lung resident CD4+ T cells were threefold higher than in FPM2e-immunized mice. This study conveys optimism as to the protective ability of a combination vaccine based on LNPs and various forms of the CTA1-DD adjuvant platform, in general, and, more specifically, an important way forward to develop a universal vaccine against influenza.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; and (Less)
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Administration, Intranasal, Animals, Antigen Presentation, Cells, Cultured, Cholera Toxin/immunology, Humans, Immunogenicity, Vaccine, Immunoglobulin A/metabolism, Influenza A virus/physiology, Influenza Vaccines/immunology, Influenza, Human/immunology, Liposomes/immunology, Lung/immunology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Nanoparticles/metabolism, Orthomyxoviridae Infections/immunology, Peptides, Cyclic, Recombinant Fusion Proteins/immunology, Th1 Cells/immunology, Th17 Cells/immunology, Vaccination
in
Mucosal Immunology
volume
14
issue
2
pages
14 pages
publisher
Elsevier
external identifiers
  • scopus:85089523447
  • pmid:32807838
ISSN
1933-0219
DOI
10.1038/s41385-020-0334-2
language
English
LU publication?
no
id
f5757b41-7c8d-4cd5-a387-9e237d2b383b
date added to LUP
2025-12-20 13:32:04
date last changed
2026-01-04 05:29:34
@article{f5757b41-7c8d-4cd5-a387-9e237d2b383b,
  abstract     = {{<p>This is a proof-of-principle study demonstrating that the combination of a cholera toxin derived adjuvant, CTA1-DD, and lipid nanoparticles (LNP) can significantly improve the immunogenicity and protective capacity of an intranasal vaccine. We explored the self-adjuvanted universal influenza vaccine candidate, CTA1-3M2e-DD (FPM2e), linked to LNPs. We found that the combined vector greatly enhanced survival against a highly virulent PR8 strain of influenza virus as compared to when mice were immunized with FPM2e alone. The combined vaccine vector enhanced early endosomal processing and peptide presentation in dendritic cells and upregulated co-stimulation. The augmenting effect was CTA1-enzyme dependent. Whereas systemic anti-M2e antibody and CD4+ T-cell responses were comparable to those of the soluble protein, the local respiratory tract IgA and the specific Th1 and Th17 responses were strongly enhanced. Surprisingly, the lung tissue did not exhibit gross pathology upon recovery from infection and M2e-specific lung resident CD4+ T cells were threefold higher than in FPM2e-immunized mice. This study conveys optimism as to the protective ability of a combination vaccine based on LNPs and various forms of the CTA1-DD adjuvant platform, in general, and, more specifically, an important way forward to develop a universal vaccine against influenza.</p>}},
  author       = {{Bernasconi, Valentina and Norling, Karin and Gribonika, Inta and Ong, Li Ching and Burazerovic, Sabina and Parveen, Nagma and Schön, Karin and Stensson, Anneli and Bally, Marta and Larson, Göran and Höök, Fredrik and Lycke, Nils}},
  issn         = {{1933-0219}},
  keywords     = {{Administration, Intranasal; Animals; Antigen Presentation; Cells, Cultured; Cholera Toxin/immunology; Humans; Immunogenicity, Vaccine; Immunoglobulin A/metabolism; Influenza A virus/physiology; Influenza Vaccines/immunology; Influenza, Human/immunology; Liposomes/immunology; Lung/immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Nanoparticles/metabolism; Orthomyxoviridae Infections/immunology; Peptides, Cyclic; Recombinant Fusion Proteins/immunology; Th1 Cells/immunology; Th17 Cells/immunology; Vaccination}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{523--536}},
  publisher    = {{Elsevier}},
  series       = {{Mucosal Immunology}},
  title        = {{A vaccine combination of lipid nanoparticles and a cholera toxin adjuvant derivative greatly improves lung protection against influenza virus infection}},
  url          = {{http://dx.doi.org/10.1038/s41385-020-0334-2}},
  doi          = {{10.1038/s41385-020-0334-2}},
  volume       = {{14}},
  year         = {{2021}},
}