Characterization of a single-cycle rabies virus-based vaccine vector

Area of Science:

• Virology
• Immunology
• Vaccine Development

Background:

• Recombinant rabies virus (RV)-based vectors are effective for inducing antigen-specific immune responses.
• Replication-competent viral vectors raise safety concerns due to pathogenicity, primarily linked to the RV glycoprotein (RV-G).

Purpose of the Study:

• To develop a safer, single-cycle RV vaccine vector by deleting the G gene.
• To evaluate the immunogenicity and safety of this modified vector (SPBN-DeltaG-Gag) compared to a replication-competent control (BNSP-Gag) for HIV-1 vaccine development.

Main Methods:

• A G-deleted RV vaccine vector expressing HIV-1 Gag (SPBN-DeltaG-Gag) was created and propagated on cells expressing RV-G.
• In vivo immunogenicity was assessed in mice, comparing SPBN-DeltaG-Gag to BNSP-Gag.
• Immune responses were measured by antibody titers, isotype profiles, CD8(+) T-cell responses (MHC class I Gag-tetramer staining, IFN-γ ELISpot, CTL assays), and response maintenance at low titers.

Main Results:

• The single-cycle RV (SPBN-DeltaG-Gag) induced lower RV-specific antibodies but similar IgG2a/IgG1 isotype profiles compared to the replication-competent control (BNSP-Gag).
• Both vectors elicited comparable Gag-specific CD8(+) T-cell responses, which were maintained at low immunization doses (10^3 FFU).
• Boosting with a single-cycle RV complemented with a heterologous glycoprotein enhanced CD8(+) T-cell responses.

Conclusions:

• Single-cycle RV vectors represent a safe and effective alternative to replication-competent RV vectors.
• These findings support the potential of single-cycle RV vectors for developing vaccines against HIV-1 and other infectious diseases.