Recombinant HIV-1 vaccine candidates based on replication-defective flavivirus vector

Area of Science:

• Virology
• Vaccinology
• Immunology

Background:

• Developing an effective HIV-1 vaccine remains a global health priority.
• Viral and DNA vectors are promising strategies for HIV vaccine development.
• Alternative vectors are needed to enhance vaccine efficacy and overcome existing limitations.

Purpose of the Study:

• To evaluate the replication-defective flavivirus vector, RepliVax (RV), for delivering HIV-1 immunogens.
• To assess the immunogenicity and safety of RV-based HIV vaccine candidates.
• To explore the potential of RV vectors in prime-boost vaccination strategies.

Main Methods:

• Engineered recombinant RV-HIV viruses expressing HIV-1 Gag and Env (gp120TM) proteins.
• Propagated RV-HIV viruses in Vero helper cells.
• Assessed RV vector apathogenicity in suckling mouse neurovirulence tests.
• Evaluated immunogenicity in mice using homologous and heterologous prime-boost regimens with NYVAC-HIV vectors.
• Conducted a pilot non-human primate (NHP) study comparing RV-HIV prime/boost with DNA and NYVAC candidates, alongside adjuvanted gp120 protein.

Main Results:

• RV-based vectors achieved efficient expression and correct maturation of HIV-1 Gag and gp120TM proteins.
• RV-HIV viruses were found to be apathogenic in neurovirulence tests.
• Immunogenicity in mice was comparable to recombinant poxvirus NYVAC-HIV vectors.
• In NHPs, RV-HIV prime/boost regimens elicited similar neutralizing antibody titers, binding IgG titers against Env and Gag antigens, and antibody-dependent cellular cytotoxicity (ADCC) responses compared to benchmark schemes.
• T cell responses were successfully elicited in NHPs.

Conclusions:

• Replication-defective flavivirus RV vectors are a viable platform for delivering HIV-1 immunogens.
• RV vectors demonstrate safety and immunogenicity comparable to established vaccine vectors.
• RV vectors hold potential as novel components in combination HIV-1 vaccine strategies.