A vaccine combination of lipid nanoparticles and a cholera toxin adjuvant derivative greatly improves lung protection against influenza virus infection
Artikel i vetenskaplig tidskrift, 2020

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.

Författare

V. Bernasconi

Göteborgs universitet

Karin Norling

Chalmers, Biologi och bioteknik, Kemisk biologi

Inta Gribonika

Göteborgs universitet

Li Ching Ong

Göteborgs universitet

Sabina Burazerovic

Chalmers, Fysik, Biologisk fysik

Nagma Parveen

Chalmers, Fysik, Biologisk fysik

Karin Schön

Göteborgs universitet

Anneli Stensson

Göteborgs universitet

Marta Bally

Umeå universitet

G. Larson

Göteborgs universitet

Fredrik Höök

Chalmers, Fysik, Nano- och biofysik

N. Y. Lycke

Göteborgs universitet

Mucosal Immunology

1933-0219 (ISSN) 1935-3456 (eISSN)

Vol. In Press

Ämneskategorier

Immunologi

Immunologi inom det medicinska området

Mikrobiologi inom det medicinska området

DOI

10.1038/s41385-020-0334-2

PubMed

32807838

Mer information

Senast uppdaterat

2020-09-24