Attenuated vesicular stomatitis viruses as vaccine vectors

Area of Science:

• Virology
• Immunology
• Vaccine Development

Background:

• Recombinant vesicular stomatitis virus (VSV) expressing influenza hemagglutinin (HA) previously showed protection against influenza.
• The prior VSV vector exhibited some pathogenesis associated with the vector itself.

Purpose of the Study:

• To develop completely attenuated VSV vectors expressing HA for intranasal vaccination.
• To evaluate the safety and efficacy of these novel vectors in a mouse model.

Main Methods:

• Generation of two new VSV vectors: CT1-HA (truncated G protein) and DeltaG-HA (deleted G protein), both expressing influenza HA.
• Intranasal administration of the vectors to mice.
• Assessment of vector pathogenesis and protective efficacy against lethal influenza virus challenge.

Main Results:

• The CT1-HA vector, with a truncated G protein, was nonpathogenic and provided complete protection from lethal influenza challenge.
• The DeltaG-HA vector, with a deleted G protein, was also nonpathogenic and protective.
• The DeltaG-HA vector did not induce neutralizing antibodies against the VSV vector itself.

Conclusions:

• Attenuated VSV vectors expressing influenza HA are safe and effective for intranasal vaccination.
• Truncation or deletion of the VSV G protein can render the vector nonpathogenic.
• The DeltaG-HA vector offers an advantage by avoiding anti-vector immunity, potentially allowing for booster vaccinations.