Multigene DNA prime-boost vaccines for SHIV89.6P.

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Simian-Human Immunodeficiency Virus (SHIV) infection in macaques causes rapid CD4+ T cell depletion, mirroring human disease.
• Developing effective vaccines against SHIV is crucial for advancing Human Immunodeficiency Virus (HIV) prevention strategies.

Purpose of the Study:

• To evaluate four prime-boost vaccine regimens incorporating a Gene Gun component for SHIV89.6P in Macaca nemestrina.
• To assess the immunogenicity and protective efficacy of DNA prime/vaccinia boost and vaccinia prime/DNA boost strategies.

Main Methods:

• Dosing experiments with beta-galactosidase plasmid determined optimal Gene Gun delivery parameters (30-45 shots/dose).
• A six-plasmid DNA vaccine encoding non-infectious virions was used in prime-boost regimens with vaccinia recombinants or inactivated virus.
• Macaques were challenged intrarectally with SHIV89.6P, and immune responses and CD4+ T cell counts were monitored.

Main Results:

• DNA prime/vaccinia boost and vaccinia prime/DNA boost regimens elicited strong immune responses.
• These two regimens protected 11 out of 12 vaccinated macaques from acute CD4+ T cell depletion following SHIV89.6P challenge.
• Other tested vaccine regimens were not effective in preventing disease or CD4+ T cell loss.

Conclusions:

• Prime-boost vaccination strategies combining DNA and vaccinia virus are highly effective in protecting macaques against SHIV challenge.
• These findings support the potential of DNA and viral vector-based vaccines for HIV/AIDS prevention.