Vaccination with attenuated simian immunodeficiency virus by DNA inoculation

Area of Science:

• Virology
• Vaccinology
• Immunology

Background:

• Attenuated lentivirus vaccines are desirable for simplicity and cost-effectiveness.
• Simian immunodeficiency virus (SIV) infection in macaques serves as a model for human immunodeficiency virus (HIV) research.
• Proviral DNA delivery is a potential vaccine strategy.

Purpose of the Study:

• To investigate the potential of attenuated SIV DNA vaccines for protection against SIV infection.
• To determine the impact of specific genetic deletions on SIV virulence and immunogenicity.

Main Methods:

• Macaca mulatta (macaques) were inoculated with wild-type SIVmac239 DNA or modified SIVmac239 DNA.
• Genetic modifications included single deletions in the 3' nef-long terminal repeat (LTR) overlap region and identical deletions in both 5' and 3' LTRs.
• Animals were subsequently challenged with pathogenic SIVmac251 via mucosal exposure.

Main Results:

• Inoculation with wild-type SIVmac239 DNA or SIVmac239 DNA with a single 3' nef/LTR deletion resulted in persistent SIV infections and AIDS.
• Macaques receiving SIVmac239 DNA with identical deletions in both 5' and 3' LTRs exhibited attenuated SIV infections.
• This attenuated SIV DNA vaccine conferred substantial protection against subsequent mucosal SIVmac251 challenge.

Conclusions:

• Genetic modification of SIV DNA, specifically deletions in LTR regions, can attenuate the virus.
• Attenuated SIV DNA vaccines demonstrate protective efficacy against homologous SIV challenge in macaques.
• This study supports the development of attenuated lentivirus DNA vaccines.