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The mucosal adjuvant 1 Endocine™ increases immune responses to influenza antigen in aged mice
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
Eurocine Vaccines AB, Karolinska Institutet Science Park, Solna, Sweden.
Eurocine Vaccines AB, Karolinska Institutet Science Park, Solna, Sweden.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

More effective influenza vaccines for the elderly population is needed. The vaccines used today are less effective in elderly compared to in adults. It is more difficult to stimulate a protective immune response in elderly due to immunosenescence. Elderly people have a decline in both humoral and cell mediated immunity, which make them more susceptible to viral infections. The aim of this study was to evaluate the mucosal adjuvant Endocine™ together with split influenza antigen in different ages of BALB/c mice (15, 20 and 25 months old). The results from this study show that a nasal influenza vaccine  formulated with Endocine™ enhanced both systemic and mucosal immune responses compared to an unadjuvanted vaccine delivered subcutaneously or intra nasal in aged mice. However, in the 25 months old mice only a very modest immune response was detected. Although the influenza-specific immune responses in aged mice were not induced to the same levels as achieved in young mice, the results show that nasal vaccine formulated with Endocine™ could provide benefits for the elderly.

National Category
Clinical Laboratory Medicine Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-117980OAI: oai:DiVA.org:liu-117980DiVA: diva2:812609
Available from: 2015-05-19 Created: 2015-05-19 Last updated: 2015-05-19Bibliographically approved
In thesis
1. Nasal vaccination using novel mucosal adjuvants: with main focus on influenza A virus
Open this publication in new window or tab >>Nasal vaccination using novel mucosal adjuvants: with main focus on influenza A virus
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Influenza viruses have sporadically caused pandemics during the last century, with the most severe occurring in 1918 when the “Spanish flu”, an A/H1N1 influenza virus, passed around the globe killing about 20-100 million people. Today 250 000-500 000 deaths occur annually due to influenza virus or secondary infection after influenza, e.g. pneumonia. Influenza viruses cause severe infections in susceptible age groups like children and elderly and in individuals with impaired immune response due to other medical conditions. The best way to prevent an influenza epidemic is by vaccination. Since the 1950´s we have vaccines against seasonal flu, but vaccine efficacy is not 100 % and there is a need to develop better and more effective vaccines, especially for the risk groups. Since the virus enters the host through the nasal cavity, nasal vaccination is a good approach. By stimulating a mucosal immune response already in the nasal cavity, the goal with nasal vaccination is to stop the virus before it enters the host. Nasal vaccination also reduces the risk of transmission of blood-borne diseases, and is less painful and easier to administer, compared to injectable vaccines.

In order to be able to use less immunogenic antigens, like split and subunit antigens, as nasal vaccine components, an adjuvant is needed to enhance the immune response. At the moment there is no licensed mucosal adjuvant for human use. Several studies are ongoing, but it is a complicated and long way to reach the market. In this thesis nasal vaccination with influenza antigen together with the mucosal adjuvant Endocine™ and other mucosal adjuvants has been evaluated. The Endocine™ adjuvant has been shown to be safe and well tolerated in clinical trials. Depending on the pathogen of interest, different approaches are necessary. For HIV, DNA-vaccination has been evaluated together with a plasmid encoding Salmonella typhimurium flagellin C and the mucosal adjuvant N3. The results found in paper I-IV show that by adding adjuvant to the antigen enhances the protective immune response towards the antigen. Enhanced systemic, mucosal and cell-mediated immunity were observed. Hopefully in the future these adjuvants evaluated in this thesis, will be used in vaccines for humans.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2015. 57 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1460
National Category
Biochemistry and Molecular Biology Immunology in the medical area
Identifiers
urn:nbn:se:liu:diva-117981 (URN)10.3384/diss.diva-117981 (DOI)978-91-7519-060-0 (print) (ISBN)
Public defence
2015-05-28, Eken, Campus US, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2015-05-19 Created: 2015-05-19 Last updated: 2015-05-19Bibliographically approved

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Falkeborn, TinaHinkula, Jorma
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