Infectivity of wild-type and deleted proviral SIV DNA

Area of Science:

• Virology
• Immunology
• Vaccine Development

Background:

• Live attenuated lentiviruses show promise as HIV vaccines, but field delivery is challenging.
• Delivering attenuated lentiviruses as proviral DNA offers a simpler immunization method, but its efficiency is unknown.

Purpose of the Study:

• To investigate the efficiency of simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) DNA delivery for immunization.
• To assess the infectivity and in vivo behavior of engineered SIV DNA constructs in macaques.

Main Methods:

• Macaques were inoculated with plasmid DNA encoding SIVmac239 via intramuscular (i.m.) or epidermal routes.
• A human skin explant model was used to determine the 50% infectious dose (ID50) of SIV/HIV-1 plasmid DNA delivered by gene gun.
• An engineered SIV clone (SIVsbbc delta3) with a nef/LTR deletion was created and tested in macaques.

Main Results:

• Macaques inoculated with SIVmac239 DNA (i.m. or epidermal) were readily infected and developed AIDS.
• The ID50 of proviral SIV/HIV-1 plasmid DNA delivered to skin via gene gun was as low as 1 microg.
• Macaques inoculated with SIVsbbc delta3 DNA were infected, and one animal showed spontaneous repair of the nef/LTR deletion, progressing to AIDS.

Conclusions:

• Proviral SIV/HIV-1 DNA can efficiently infect macaques via i.m. or epidermal delivery, and via gene gun delivery to skin.
• The spontaneous repair of the nef/LTR deletion in vivo suggests potential complexities and risks associated with SIV/HIV DNA vaccine strategies.
• Further research is needed to understand the mechanisms of deletion repair and its implications for vaccine safety and efficacy.