Protein Priming Followed by a Replication-Competent VSV-GP Vector Boost Induces Sustained Immune Control in...

Area of Science:

• Immunology
• Vaccinology
• Hepatology

Background:

• Chronic hepatitis B (CHB) remains a global health challenge, necessitating effective therapeutic vaccines.
• The heterologous protein prime/viral vector boost strategy (TherVacB) shows promise for CHB treatment.
• Novel viral vectors are being explored to enhance vaccine efficacy.

Purpose of the Study:

• To evaluate a replication-competent chimeric vesicular stomatitis virus vector (VSV-GP) co-expressing HBV antigens (VSV-GP-HBs/c) as a boost vaccine.
• To assess the immunogenicity, antiviral efficacy, and durability of VSV-GP-HBs/c in different vaccination regimens.
• To determine the optimal strategy for therapeutic vaccination against CHB.

Main Methods:

• Generation and characterization of recombinant VSV-GP vector (VSV-GP-HBs/c) expressing HBV surface and core antigens.
• Assessment of immunogenicity and antiviral efficacy in HBV-naïve and HBV-carrier mouse models.
• Comparison of vaccination regimens including protein prime, viral vector prime, and heterologous prime-boost strategies.

Main Results:

• VSV-GP-HBs/c efficiently expressed HBV antigens in vitro.
• A single VSV-GP-HBs/c immunization induced weak immune responses; protein priming followed by VSV-GP-HBs/c boost elicited robust HBV-specific antibody and T-cell immunity.
• The protein prime/VSV-GP-HBs/c boost regimen significantly reduced HBV markers (HBsAg, HBV-DNA, infected hepatocytes), comparable to the TherVacB regimen.
• A single VSV-GP-HBs/c boost achieved sustained antiviral control, and a second viral vector boost did not improve efficacy.

Conclusions:

• VSV-GP-HBs/c is an effective viral vector for boosting immune responses in therapeutic hepatitis B vaccination.
• A single protein prime followed by a single VSV-GP-HBs/c viral vector boost is an optimal strategy for achieving sustained antiviral immunity against CHB.
• This approach offers a promising avenue for a functional cure of chronic hepatitis B.