Prüfung der Schutzwirkung eines trivalenten Influenzavirus-Inaktivatimpfstoffs für Schweine in Infektionsversuchen mit aktuellen Feld stämmen der Subtypen H1N1, H3N2 und H1N2

Zusammenfassung:

Gegenstand und Ziel: Die Integration eines humanen H1-Hämagglutinins mit fehlender Kreuzreaktivität zu “Avian-like-” und “Classical-swine”-H1N1-Stämmen über ein natürliches Reassortment in europäische porzine Influenzaviren hat die bisher relativ stabile epidemiologische Situation der Schweineinfluenza gravierend verändert. Grund dafür ist die entstandene Lücke in der Immunprophylaxe, die durch die verfügbaren H1N1+H3N2-Impfstoffe nicht mehr geschlossen werden kann und somit die Einbeziehung des neuen Subtyps H1N2 als Impfantigen in Impfstoffe erfordert. Ziel der Untersuchungen war, in Vorbereitung der Entwicklungsphase eines neuen, trivalenten Impfstoffes zu prüfen, ob solch ein Impfstoff vor Belastungsinfektionen mit Stämmen aller drei Subtypen schützt. Material und Methoden: Aktuelle Influenzavirusstämme der Subtypen H1N1, H3N2 und H1N2, die in Gegenden mit hoher Schweinedichte isoliert worden waren, wurden als Impfstämme selektiert, in Zellkulturen produziert, inaktiviert und daraus ein Labormuster mit einem verträglichen Adjuvans hergestellt. Schweine wurden immunisiert und aerogenen Belastungsinfektionen mit aktuellen Feldisolaten ausgesetzt. Ergebnisse: Die Impfung induzierte bereits 7 Tage nach Abschluss der Grundimmunisierung hämagglutinationshemmende und neutralisierende Antikörper. Nach experimenteller Infektion waren immunisierte Schweine vollständig geschützt, zeigten im Vergleich zu nicht immunisierten Kontrolltieren keine oder mildere Symptome sowie eine signifikant geringere Viruslast in den Lungen und schieden signifikant weniger Virus aus. Schlussfolgerungen: Die Entwicklung eines neuen, trivalenten Influenzavirusimpfstoffs für Schweine ist möglich, der effektiv gegenüber allen drei Subtypen einschließlich der neuen Antigenkombination H1N2 schützt.

Summary:

Subject matter and objective: The introduction via natural reassortment of a human H1 haemagglutinin that lacks cross-reactivity to avian and classical porcine H1N1 viruses into the European swine influenza A virus population has remarkably changed the otherwise epidemiologically very stable situation of swine flu. A gap therefore arose in the control of swine influenza because of the failure of inactivated H1N1 + H3N2 vaccines to provide protection against the newly emerged H1N2 subtype. The epidemiological situation forced the introduction of the new subtype into swine flu vaccines. Aim of the investigations was to prove the efficacy of a newly developed trivalent swine flu vaccine by challenges with field strains of all three subtypes. Materials and methods: Three virus strains of subtypes H1N1, H3N2, and H1N2 originally isolated in regions with dense swine populations were chosen as vaccine strains; these were produced in cell culture, inactivated and finally blended into an experimental vaccine. Pigs were vaccinated and submitted to a challenge infection once primary immunization was complete. An aerosol-mediated challenge procedure was applied to investigate efficacy of the vaccine by using current field strains of each subtype. Results: Vaccinated pigs displayed neutralizing and haemagglutination inhibiting antibodies as early as 7 days after the second vaccination, which is the onset of immunity. Vaccinated animals had no clinical symptoms after infection, whereas unvaccinated animals exhibited fever and dyspnoea especially after H3N2 and H1N2 infections. The viral load in the lungs was significantly lower in vaccinated pigs compared to unvaccinated animals. Vaccinated pigs shed significantly lower amounts of virus in comparison to unvaccinated pigs. Conclusions: The development of a new trivalent swine flu vaccine that provides protection against all three subtypes, including the new subtype H1N2 is feasible and improves safety through the use of a nonpyrogenic adjuvant.

Schlüsselwörter:

Schweineinfluenza - H1N1 - H3N2 - H1N2 - trivalenter Impfstoff

Key words:

Swine influenza - H1N1 - H3N2 - H1N2 - trivalent vaccine

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