Protection against simian immunodeficiency virus vaginal challenge by using Sabin poliovirus vectors

Area of Science:

• Virology
• Immunology
• Vaccinology

Background:

• Developing effective vaccines against simian immunodeficiency virus (SIV) is crucial for understanding and combating human immunodeficiency virus (HIV).
• Poliovirus vectors offer a potential platform for vaccine development due to their safety and immunogenicity.

Purpose of the Study:

• To evaluate the efficacy of novel poliovirus-based vaccine vectors expressing simian immunodeficiency virus (SIV) antigens against vaginal SIV challenge.
• To assess the immune responses generated by these vaccine vectors in non-human primates.

Main Methods:

• Construction of transgenic polioviruses (SabRV1-SIV and SabRV2-SIV) containing SIV gag, pol, env, nef, and tat fragments.
• Inoculation of cynomolgus macaques with vaccine cocktails and subsequent vaginal challenge with pathogenic SIVmac251.
• Monitoring of virological, immunological (antibody and cytotoxic T-lymphocyte responses), and clinical parameters post-vaccination and challenge.

Main Results:

• Vaccinated macaques developed significant anti-SIV antibody and mucosal responses, with detectable SIV-specific cytotoxic T-lymphocyte responses in some.
• Four out of seven vaccinated animals showed substantial protection against SIV vaginal challenge, with two exhibiting complete protection (no detectable infection).
• Vaccinated animals remained clinically healthy, while control animals became infected and some developed AIDS, indicating vaccine efficacy.

Conclusions:

• Poliovirus-based vaccine vectors (SabRV) are effective in inducing protective immunity against SIV vaginal challenge in macaques.
• A vaccine strategy using a cocktail of vectors expressing diverse SIV antigens can be successful in an outbred population.
• SabRV demonstrates potential as a human vaccine vector for preventing lentiviral infections.