Immunoprophylaxis against AIDS in macaques with a lentiviral DNA vaccine

• Published in: Virology (New York, N.Y.) Vol. 351; no. 2; pp. 444 - 454
• Main Authors: Liu, ZhenQian, Singh, Dinesh K., Sheffer, Darlene, Smith, Marilyn S., Dhillon, Sukhbir, Chebloune, Yahia, Hegde, Ramakrishna, Buch, Shilpa, Narayan, Opendra
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2006; Elsevier
• Subjects: AIDS; Animals; CD4 Lymphocyte Count; Cell Line; DNA Vaccines; Human immunodeficiency virus; Humans; Lentivirus - genetics; Life Sciences; Macaca; Macaca fascicularis; Macaque; SAIDS Vaccines - genetics; SAIDS Vaccines - immunology; SHIV; Simian Acquired Immunodeficiency Syndrome - immunology; Simian Acquired Immunodeficiency Syndrome - prevention & control; Simian Immunodeficiency Virus; Simian virus 40; Time Factors; Vaccines, DNA - genetics; Vaccines, DNA - immunology; DNA Vaccines; Macaque; AIDS; SHIV; DNA VACCINES; MACAQUE
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2006.03.033

We earlier reported that immunization of macaques with a reverse transcriptase-deleted SHIV KU2 (Δ rtSHIV KU2) plasmid that contained HIV-1(HXB2) env and SIV gag–nef induced protection against AIDS caused by challenge virus SHIV89.6P with a heterologous env. We further deleted vif and integrase from Δ rtSHIV KU2 and substituted the 3′LTR with SV40 poly A sequences, creating Δ4SHIV KU2 (M) and a parallel construct containing gag–nef of HIV-1 SF2, Δ4SHIV KU2 (H). Six macaques received two intramuscular injections of the (M) DNA, and another six received three injections of the (H) DNA. Three of the latter group received two post-challenge boosts with (M) DNA vaccine . Seven virus control macaques were inoculated with SHIV89.6P. All twelve immunized macaques were challenged with SHIV89.6P virus, and CMI responses were measured by ELISPOT assays. Virus control animals all developed progressive infection, whereas vaccinated macaques from both groups controlled virus replication, with plasma viral loads dropping to undetectable levels between weeks 6 and 126 p.i. This DNA vaccine was efficacious even though it encoded Env, Gag, and Nef that were genetically distinct from the proteins in the challenge virus. The DNA vaccine induced broad-based protection without using viral proteins to boost the immunity.