Protective Effects of a Live Attenuated SIV Vaccine with a Deletion in the nef Gene

Abstract

Vaccine protection against the human immunodeficiency virus (HIV) and the related simian immunodeficiency virus (SIV) in animal models is proving to be a difficult task. The difficulty is due in large part to the persistent, unrelenting nature of HIV and SIV infection once infection is initiated. SIV with a constructed deletion in the auxiliary gene nef replicates poorly in rhesus monkeys and appears to be nonpathogenic in this normally susceptible host. Rhesus monkeys vaccinated with live SIV deleted in nef were completely protected against challenge by intravenous inoculation of live, pathogenic SIV. Deletion of nef or of multiple genetic elements from HIV may provide the means for creating a safe, effective, live attenuated vaccine to protect against acquired immunodeficiency syndrome (AIDS).

CD8 + Lymphocytes Do Not Mediate Protection against Acute Superinfection 20 Days after Vaccination with a Live Attenuated Simian Immunodeficiency Virus

“…Live attenuated SIV vaccines can confer effective protection against detectable superinfection with pathogenic, wild-type SIV (3,13,14,29,58,59) and SIV/HIV-1 chimeric virus (7,18,46). Yet there are limits to the breadth of this protection, and live attenuated SIV vaccines have failed to protect against certain heterologous challenge viruses or failed to protect against a challenge performed several years postinoculation (22,31,58).…”

Partial protection against SIV challenge by vaccination of adenovirus and MVA vectors in rhesus monkeys

“…Because of the safety concerns and inadequate protection of the more attenuated liveattenuated vaccine, the vaccine field is currently not actively pursuing live-attenuated vaccines for use in humans. 1,4,6,[27][28][29][30] Previously, the efficacy of various Adand MVA-based vaccines about the susceptibility to SHIV infection in monkeys has been examined by our research group and other scientists. 10,24 This study investigates whether a combination of these vaccines can prevent SIV infection.…”

“…Vaccination of rhesus monkeys with live-attenuated simian immunodeficiency virus (SIV) vaccine was shown to provide protective immunity against disease after challenge with pathogenic SIV. [1][2][3][4] However, the live-attenuated SIV/HIV possesses the potential risk of the vaccine virus reverting to a pathogenic form. Indeed, a study in which 11 adult monkeys were vaccinated with SIVmac239Delta3 reported that in the 6.8-year period after vaccination, all the monkeys had signs of immune dysregulation, 64% of the monkeys had persistent recurrent viremia, and 18% of the monkeys developed AIDS.…”

Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions

“…Subsequent studies, however, demonstrated that Nef plays an important role in several steps of HIV replication. In addition, it appears to be a critical pathogenic factor, as Nef-deficient SIV and HIV are significantly less pathogenic than the wild-type viruses [95][96][97], whereas Neftransgenic mice show many features characteristic to HIV disease [98,99].…”