Abstract:
:The current seasonal inactivated influenza vaccine protects only against a narrow range of virus strains as it triggers a dominant antibody response toward the hypervariable hemagglutinin (HA) head region. The discovery of rare broadly protective antibodies against conserved regions in influenza virus proteins has propelled research on distinct antigens and delivery methods to efficiently induce broad immunity toward drifted or shifted virus strains. Here, we report that adeno-associated virus (AAV) vectors expressing influenza virus HA or chimeric HA protected mice against homologous and heterologous virus challenges. Unexpectedly, immunization even with wild-type HA induced antibodies recognizing the HA-stalk and activating FcγR-dependent responses indicating that AAV-vectored expression balances HA head- and HA stalk-specific humoral responses. Immunization with AAV-HA partially protected also ferrets against a harsh virus challenge. Results from this study provide a rationale for further clinical development of AAV vectors as influenza vaccine platform, which could benefit from their approved use in human gene therapy.
journal_name
EMBO Mol Medjournal_title
EMBO molecular medicineauthors
Demminger DE,Walz L,Dietert K,Hoffmann H,Planz O,Gruber AD,von Messling V,Wolff Tdoi
10.15252/emmm.201910938subject
Has Abstractpub_date
2020-05-08 00:00:00pages
e10938issue
5eissn
1757-4676issn
1757-4684journal_volume
12pub_type
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