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Blood. 2016 Mar 31. pii: blood-2015-11-679282. [Epub ahead of print]

Concurrent influenza vaccination reduces anti-FVIII antibody responses in hemophilia A mice via chemotactic antigen competition.

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  • 1Department of Pathology & Molecular Medicine, Queen's University, Kingston, ON, Canada;
  • 2Discipline of Pediatrics, Faculty of Medicine, Memorial University, Section of Pediatric Hematology/Oncology, Janeway Children's Health and Rehabilitation Centre, St. John's, NL, Canada;
  • 3Baxalta Innovation GmbH, Vienna, Austria.
  • 4Department of Pathology & Molecular Medicine, Queen's University, Kingston, ON, Canada;


Inflammatory signals such as pathogen- and danger-associated molecular patterns have been hypothesized as risk factors for the initiation of the anti-FVIII immune response seen in 25-30% of patients with severe hemophilia A. In these young patients, vaccines may be coincidentally administered in close proximity with initial exposure to FVIII, thereby providing a source of such stimuli. Here, we investigated the effects of 3 vaccines commonly used in pediatric patients on FVIII immunogenicity in a humanized HA murine model with variable tolerance to recombinant human FVIII (rhFVIII). Mice vaccinated intramuscularly against the influenza vaccine prior to multiple infusions of rhFVIII, exhibited a decreased incidence of rhFVIII-specific neutralizing and non-neutralizing antibodies. Similar findings were observed with the addition of an adjuvant. Upon exposure to media from influenza- or FVIII-stimulated lymph node or splenic lymphocytes, naïve CD4+lymphocytes preferentially migrated towards media from influenza-stimulated cells, indicating that antigen competition, by means of lymphocyte recruitment to the immunization site, is a potential mechanism for the observed decrease in FVIII immunogenicity. We also observed no differences in incidence or titre of rhFVIII-specific antibodies and inhibitors in mice exposed to the live-attenuated measles-mumps-rubella vaccine regardless of route of administration. Together, our results suggest that concomitant FVIII exposure and vaccination against influenza does not increase the risk of inhibitor formation, and may in fact decrease anti-FVIII immune responses.

Copyright © 2016 American Society of Hematology.

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