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Updated: Mar 23, 2026
A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies
Published on: February 23, 2018
Concurrent influenza vaccination reduces anti-FVIII antibody responses in murine hemophilia A
Jesse D Lai1, Paul C Moorehead2, Kate Sponagle1
1Department of Pathology & Molecular Medicine, Queen's University, Kingston, ON, Canada;
Abstract:
Inflammatory signals such as pathogen- and danger-associated molecular patterns have been hypothesized as risk factors for the initiation of the anti-factor VIII (FVIII) immune response seen in 25% to 30% of patients with severe hemophilia A (HA). 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 nonneutralizing 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 toward 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 titer 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.
Insights
Vaccination against influenza may decrease the risk of developing antibodies against factor VIII (FVIII) in patients with hemophilia A (HA). This study suggests influenza vaccination does not increase FVIII inhibitor formation in a murine model.
Area of Science:
- Immunology
- Vaccinology
- Hematology
Background:
- * A significant percentage of severe hemophilia A (HA) patients develop anti-factor VIII (FVIII) antibodies, complicating treatment.
- * Inflammatory triggers, potentially including routine childhood vaccines, are hypothesized to initiate this immune response.
- * The interaction between FVIII exposure and vaccine administration timing in HA patients requires further investigation.
Purpose of the Study:
- * To investigate the impact of common pediatric vaccines on FVIII immunogenicity in a humanized hemophilia A murine model.
- * To explore potential mechanisms, such as antigen competition, underlying observed immune responses.
- * To assess the safety of co-administration of FVIII and specific vaccines regarding inhibitor development.
Main Methods:
- * A humanized hemophilia A murine model was used to assess immune responses to recombinant human FVIII (rhFVIII).
- * Mice were vaccinated with influenza vaccine or measles-mumps-rubella vaccine before rhFVIII infusions.
- * Lymphocyte migration patterns were analyzed in response to influenza- and FVIII-stimulated cell media.
Main Results:
- * Influenza vaccination prior to rhFVIII exposure decreased the incidence of anti-FVIII antibodies.
- * Adjuvants combined with influenza vaccine also showed a similar reduction in immunogenicity.
- * Naïve CD4(+) lymphocyte migration favored influenza-stimulated sites, suggesting antigen competition.
- * Measles-mumps-rubella vaccination did not alter anti-FVIII antibody or inhibitor incidence.
Conclusions:
- * Concomitant influenza vaccination and FVIII exposure in this model did not increase inhibitor risk.
- * Influenza vaccination may potentially reduce the incidence of anti-FVIII immune responses in hemophilia A.
- * Antigen competition is a plausible mechanism for the observed modulation of FVIII immunogenicity.
