Abstract
Background Influenza viruses containing chimeric hemagglutinin (HA) glycoproteins with large foreign polypeptide insertions are being examined as a novel vaccine vectors. Our initial studies involved polypeptide insertions derived from the Bacillus anthracis protective antigen (PA), and showed that the entire140 amino acid receptor binding domain of PA could be incorporated into functional chimeric PA/HA proteins. These were engineered into infectious influenza viruses by reverse genetics, and the resulting viruses displayed replication properties similar to WT influenza virus. Using a mouse model, we examined the induction of antibody responses using heterologous prime/boost strategies with a variety of PA vectors (influenza, vaccinia, rabies, cDNA), and we found that strategies involving initial priming with the influenza vector resulted in anti-PA serum antibody titers that were 10fold higher than alternative regimes. These sera displayed in vitro neutralization titers against anthrax toxin that were remarkably high, >10-fold greater than values considered to be neutralization positive, and animal protection experiments are currently underway.
Highlights
Influenza viruses containing chimeric hemagglutinin (HA) glycoproteins with large foreign polypeptide insertions are being examined as a novel vaccine vectors
Our initial studies involved polypeptide insertions derived from the Bacillus anthracis protective antigen (PA), and showed that the entire140 amino acid receptor binding domain of PA could be incorporated into functional chimeric PA/HA proteins
We examined the induction of antibody responses using heterologous prime/boost strategies with a variety of PA vectors, and we found that strategies involving initial priming with the influenza vector resulted in anti-PA serum antibody titers that were 10fold higher than alternative regimes
Summary
Influenza viruses containing chimeric hemagglutinin (HA) glycoproteins with large foreign polypeptide insertions are being examined as a novel vaccine vectors. Novel HIV vaccines using chimeric influenza HA vectors DA Steinhauer*, WA Langley, G Talekar and Z Li
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