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Broadly protective nanoparticle-based mucosal vaccine against influenza virus infection

Doctoral thesis
Authors Valentina Bernasconi
Date of public defense 2018-11-30
ISBN 978-91-7833-152-9
Publication year 2018
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Language en
Links https://gupea.ub.gu.se/handle/2077/...
Keywords Mucosal vaccination, Influenza A virus, CTA1-DD, Nanoparticle, Targeted adjuvant, Nasal immunization, Oral immunization, Neonatal vaccine, Universal vaccine
Subject categories Infectious Medicine

Abstract

Influenza is one of the major viral diseases affecting humans and it is responsible for three to five million cases of severe illness and about 250.000 to 500.000 deaths each year worldwide. A vaccine against pandemic influenza infection is much warranted and the most effective measure to reduce the risk of a global spread of novel emerging influenza strains. While injectable vaccines require trained medical staff and carry a substantial risk of spreading contaminating infections, mucosal vaccines are easier to administer and considered safer, but, unfortunately, also less effective. However, mucosal vaccines can be made more effective by using better formulations and adjuvants. We have designed two intranasal vaccine candidates against pandemic flu, which were based on the strain-conserved M2e peptide incorporated into the CTA1-DD mucosal adjuvant. Previously, the CTA1-3M2e-DD fusion protein was found to stimulate protective immunity. Here, we attempted to further improve its vaccine qualities by incorporating it into polysaccharide or liposome nanoparticles, which were administered intranasally. Our findings clearly indicate that mucosal vaccines based on combinations of the potent CTA1-DD immunomodulator and nanoparticles provide a strong basis for future mucosal vaccine development. Finally, my thesis work conveys optimism about the possibility to develop a broadly protective mucosal influenza vaccine not only for adults, but also for young children.

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