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Impact of pre-existing immunity on the induction of functional cross-reactive anti-hemagglutinin stalk antibodies following vaccination with an AS03 adjuvanted pandemic H1N1 vaccine
Institution:1. The Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway;2. K.G. Jebsen Centre for Influenza Vaccine Research, Department of Clinical Science, University of Bergen, Bergen, Norway;3. Department of Research & Development, Bergen Clinical Vaccine Consortium, Haukeland University Hospital, Bergen, Norway;4. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, USA;1. National Institute of Hygiene and Epidemiology, Hanoi, Viet Nam;2. Pediatric Center, Hue Central Hospital, Hue, Viet Nam;3. Hai Phong Children Hospital, Hai Phong, Viet Nam;4. Centers for Disease Control and Prevention, USA;1. Academy of Preventive Medicine, Shandong University, Jinan, China;2. Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, China;1. Unité des Maladies à potentiel Epidémique, Maladies Emergentes et Zoonoses (UMEMEZ), Département Biomédical et Santé Publique, Institut de Recherche en Sciences de la Santé (IRSS), 399, Avenue de la Liberté 01, BP 545, Bobo-Dioulasso, Burkina Faso;2. Ecole Nationale de l’Elevage et de la Santé Animale (ENESA), Secteur 28, Ouagadougou, Burkina Faso;3. Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health (LIH), 29 rue Henri Koch, L-4354, Esch-sur-Alzette, Luxembourg;4. Laboratoire de Recherche et d’Enseignement en Santé et Biotechnologies Animales (LARESBA), Université Nazi Boni, 01 BP 109, Bobo-Dioulasso, Burkina Faso;1. Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5A, 02‐106, Warsaw, Poland;2. Department of Poultry Diseases, National Veterinary Research Institute, Al. Partyzantow 57, 24-100, Pulawy, Poland
Abstract:The 2009 pandemic H1N1 (A(H1N1)pdm09) virus had a highly divergent hemagglutinin (HA) compared to pre-2009 seasonal H1N1 strains. Most peoples were immunologically naïve to the A(H1N1)pdm09, although hospital workers were exposed early in the pandemic before pandemic vaccines became available. Here, we evaluated how pre-existing antibodies influence the induction of cross-functional HA stalk antibodies following A(H1N1)pdm09 vaccination.Fifty-six healthcare workers vaccinated with AS03 adjuvanted A(H1N1)pdm09 vaccine were chosen by their pre-vaccination priming status (primed HI titers ≥ 40 or unprimed < 40). We analyzed the HA head- and stalk-specific serum IgG subclasses at pre- and 21 days post-vaccination. We also assessed the functionality of the HA stalk-specific antibodies to neutralize virus and mediate antibody dependent cellular cytotoxicity (ADCC).Primed individuals had higher pre-existing HA head- and stalk-specific IgG1, as well as higher ADCC functionality of stalk antibodies. However, following vaccination with the adjuvanted pandemic vaccine, only the quantity of HA head specific IgG1 antibodies were significantly higher than in unprimed individuals. The priming status did not impact upon the cross-reactive HA stalk specific IgG antibodies or their ability to neutralize virus or induce ADCC post-vaccination. In conclusion, a single dose of AS03 adjuvanted pandemic vaccine elicited similar levels of functional antibodies in naïve and primed individuals. These findings are important for understanding the immunological factors that impact or modulate pandemic vaccine responses in humans.
Keywords:Influenza  Pandemic vaccination  Priming  Immunity  Cross-reactive  Stalk antibodies
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