Strategies for improving Influenza vaccines: insights from the Influenza A H1N1 and SARS-CoV-2 pandemics

Influensa er et luftveisvirus som kan forårsake alvorlig sykdom og under stadig forandring (drift). Dagens influensavaksiner gir begrenset beskyttelse mot slike driftede influensavirus. Dette fører til at vaksinesammensetningen må revurderes på halvårlig basis, og årlig vaksinasjon anbefales til høyrisikogrupper. Målet med denne avhandlingen var å studere immunresponser etter vaksinasjon og infeksjon med influensavirus og koronaviruset Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), med et overordnet mål om å forbedre fremtidige influensavaksiner. Vi studerte antistoffresponser mot overflate-proteinet neuraminidase (NA) på influensaviruset etter infeksjon og vaksinasjon. Vi ville studere dette proteinets potensiale til å aktivere bredere immunresponser og evne til å forbedre eksisterende influensavaksiner. Vi fant at den pandemiske H1N1-vaksinen med AS03-adjuvans induserte langvarige NA-antistoffresponser og at NA var svært immunogent, selv i lave mengder. Vi fant også at årlig sesongvaksinasjon bidro til å vedlikeholde antistofftiter mot NA, men resulterte i reduserte serokonversjon, målt som en stigning i NA-antistoffer. Våre funn støtter bruken av adjuvanser for å øke NA-immunogenisiteten til influensavaksiner, samtidig som de understreker behovet for en standardisering av NA-komponenten i eksisterende vaksiner. Videre ble humane anti-NA monoklonale antistoffer isolert og karakterisert etter pandemisk H1N1-infeksjon i 2009. De monoklonale antistoffene hadde kraftig NA-hemmende aktivitet in vitro og beskyttet også mot infeksjon med influensa A H1N1 og H5N1 virus in vivo. Dette arbeidet ledet til oppdagelsen av en svært konservert epitop på N1 NA, som en kan dra nytte av i fremtidige NA-baserte vaksineformuleringer. Messenger RNA (mRNA)-vaksiner mot SARS-CoV-2 har vært svært vellykkede under Covid-19-pandemien, og mRNA-vaksiner fremstår nå som en lovende vaksineplattform for neste generasjons influensavaksiner. Vi sammenlignet kinetikken og varigheten av immunresponser etter vaksinasjon og infeksjon hos unge og eldre voksne. Våre funn indikerer at eldre kan ha behov for et annerledes vaksinasjonsregime enn yngre for å oppnå en gunstig beskyttelse. Denne innsikten bidrar til å utvikle nye, fremtidige mRNA-vaksinasjonsanbefalinger til denne høyrisikogruppen.Current seasonal influenza vaccines provide limited protection against antigenically drifted influenza viruses. Consequently, vaccine compositions must be re-evaluated on a biannual basis and annual vaccination is recommended for high-risk groups. The objective of this thesis was to study immune responses after vaccination and infection with influenza virus and severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), with the overarching aim of informing strategies for improving future influenza vaccines. Here, we investigated the antibody response to neuraminidase (NA), the second most abundant surface glycoprotein of the influenza virus, after infection and vaccination to explore its potential as a target for broader protection against influenza. We found that AS03 adjuvanted pandemic H1N1 vaccination induced durable NA antibody responses and that NA was highly immunogenic, even with low doses in the vaccine. We also found that repeated seasonal vaccination led to maintenance of NA inhibition (NAI) titres but also to reduced seroconversion rates. Our findings support inclusion of adjuvants to increase NA immunogenicity of influenza vaccines and highlights the need for standardisation of the NA component of current vaccines. Furthermore, we isolated and characterised human anti-NA monoclonal antibodies (mAbs) after pandemic H1N1 infection in 2009. The mAbs had potent NA inhibition activity in vitro and they also protected against lethal challenge with influenza A H1N1 and H5N1 viruses in vivo. This work led to the discovery of a highly conserved epitope on the N1 NA that can guide rational design of future NA-based vaccines. Messenger RNA (mRNA) vaccines against SARS-CoV-2 have been highly successful during the coronavirus disease 19 (COVID-19) pandemic and are now emerging as a promising vaccine platform for next-generation influenza vaccines. We have broadly investigated the kinetics and durability of immune responses after vaccination and infection in young and elderly. Our findings indicate that different vaccination regimen may be needed for optimal protection in older adults and can inform immunisation regimens for mRNA vaccination in this high-risk group in the future.Doktorgradsavhandlin

Selvskading

Studentarbeid i sykepleie (bachelorgrad) - Høgskolen i Bodø, 201

Establishing the Convergent Validity of the Travel Habit Questions in the Health Behavior in School-Aged Children Questionnaire by Quantifying Active Travel in Norwegian Adolescents

Background: Active travel (cycling or walking to school) can be a substantial part of adolescents' daily physical activity. Research on transport activities primarily relies on self-reported indices of travel mode and travel time. However, many researchers do not report the psychometric properties of their instruments. The Health Behavior in School-aged Children (HBSC) questionnaire is a commonly used instrument, but the items in this questionnaire on travel habits have not yet been validated. The present study was conducted to investigate the convergent validity and agreement between the HBSC items and a travel diary on (1) transport mode to and from school and (2) travel time to school. Methods: The study sample consisted of 50 participants in the 9th grade (15 ± 0.3 years, 62% girls) from seven Norwegian schools. Outcome variables included transport mode and travel time derived from the HBSC items and a five-day travel diary. Convergent validity was assessed by evaluating Cohen's kappa for travel mode and the correlation coefficient (Spearman Rho) for travel time. Simple agreement calculations between the two measurement methods were also conducted. Results: The association between the HBSC questionnaire and the diary for travel mode to and from school was κ = 0.63 (P < 0.001) and κ = 0.77 (P < 0.001), respectively. The total agreement between the HBSC questionnaire and the diary for was 78%. However, the agreement was higher for walking (88%) and cycling (91%) than for motorized transport (67%). For travel time, the Spearman correlation coefficient was ρ = 0.60 (P < 0.001) between the HBSC questionnaire and the diary. The total agreement on travel time was 67%; however, active commuters (86%) seemed to more accurately estimated travel time than motorized commuters (55%). Conclusion: Although the overall agreement between the HBSC questionnaire and the diary for mode of transport was 78%, the HBSC questionnaire may underestimate the prevalence of motorized transport compared to walking and cycling.publishedVersio

Struktur: Eigenschaftsbeziehungen chalkogenidbasierter Schichtmaterialien

Im Rahmen dieser Arbeit wurden unterschiedliche Materialien basierend auf chalkogenidischen Schichtmaterialien in Bezug auf deren Struktur-Eigenschaftsbeziehungen untersucht. Das Hauptaugenmerk lag auf der Charakterisierung mit Röntgenbeugungsmethoden, da diese Methoden erlauben, die Realstruktur eines Materials auf globaler Ebene zu erfassen

Deutsche Organspende-Kampagnen zwischen 1996 und 2016: eine empirisch-ethische Kontextanalyse

Seit der Verabschiedung des Transplantationsgesetzes (TPG) im Jahr 1996 werden in Deutschland massenmediale Kampagnen zur Organtransplantation verbreitet. Plakataktionen sind ein wichtiger Teil dieser Kampagnen. In diesem Aufsatz wird die historische Entwicklung der Plakate mittels einer Kontextanalyse rekonstruiert, gestützt durch Expert*inneninterviews und multimodale Inhaltsanalysen. Dadurch werden Veränderungen identifiziert und die Kampagnenlandschaft wird als gewachsene Praxis von Akteuren des Gesundheitssystems reflektiert. Es zeigt sich erstens, dass die Kampagnen eng mit der Entwicklung des deutschen Transplantationswesens verknüpft sind. Ihre Ziele sind erklärungs- bzw. legitimierungsbedürftig: Aus historischer Sicht können sie sich mit ihren Kontexten ändern. Aus ethischer Sicht ist zentral, ob bestimmte Ziele der Kampagnen konfligieren und wie diese Konflikte so gelöst werden können, dass sie möglichst wenig Schaden erzeugen. Es zeigt sich zweitens, dass Akteure auf Zäsuren im Transplantationswesen mit persuasiven Kommunikationsstrategien zur Erhöhung der Organspendebereitschaft reagierten. Zunehmend ist jedoch eine Offenheit in der Wahl der Botschaften zu erkennen und den Plakaten liegt heute die Förderung einer selbstbestimmten und gut informierten Entscheidung zu Grunde - ein zukunftsweisender Weg für das Gesetz zur Stärkung der Entscheidungsbereitschaft bei der Organspende, welches 2022 in Kraft getreten ist.Since the passing of the Transplantation Act (TPG) in 1996, mass media campaigns on organ donation have been disseminated in Germany. Public posters are an important part of these campaigns. I reconstruct historical changes of such psoters through a context analysis, supported by expert interviews and a multimodal content analysis. Thus, changes are identified and campaigns are reflected as an evolved practice of actors in the health care system. First, it is shown that the campaigns are closely linked to the development of the German transplantation system. Their goals require explanation and legitimization: from a historical perspective, goals may change with their contexts. From an ethical point of view, it is central whether certain goals of the campaigns conflict and how these conflicts can be resolved in such a way that they produce as little harm as possible. Second, it is apparent that actors have responded to changes in transplantation with persuasive communication strategies to increase willingness to donate organs. However, the choice of messages has changed. Today, posters are based on promoting self-determined and well-informed decision-making - a promising path for the next legal revision, which came into force in 2022