Arenavirus-Based Vectors Generate Robust SIV Immunity in Non-Human Primates

Area of Science:

• Vaccinology
• Immunology
• Viral Vector Technology

Background:

• Arenavirus-based vectors are emerging as promising candidates for therapeutic vaccines.
• These vectors have the potential to induce significant CD8 T-cell responses, crucial for combating viral infections like HIV.

Purpose of the Study:

• To compare the immunogenicity of replicating and non-replicating arenavirus vectors expressing simian immunodeficiency virus (SIV) antigens.
• To evaluate the efficacy of homologous versus heterologous prime-boost regimens in non-human primates.

Main Methods:

• Non-human primates received either replicating (artPICV, artLCMV) or non-replicating (rPICV, rLCMV) arenavirus vectors encoding SIV Gag and Env immunogens.
• Immunogenicity was assessed by measuring SIV-specific interferon-gamma (IFN-γ) responses and anti-Env antibody titers.
• Different immunization routes (intravenous and intramuscular) and regimens (homologous and heterologous) were compared.

Main Results:

• Heterologous regimens induced more robust SIV IFN-γ responses than homologous regimens.
• Replicating vectors elicited significantly higher cellular immunogenicity compared to non-replicating vectors.
• Intravenous administration of heterologous regimens resulted in high anti-Env antibody titers, with replicating vectors showing superior induction.
• Intramuscular immunization led to more durable antibody responses than intravenous immunization for both vector types.

Conclusions:

• Both replicating and non-replicating arenavirus vectors effectively generate T- and B-cell immunity against SIV antigens in non-human primates.
• These findings support the further clinical development of arenavirus vectors as therapeutic vaccines for HIV.
• Heterologous prime-boost strategies and the use of replicating vectors may enhance vaccine efficacy.