Evaluation of recombinant Kunjin replicon SIV vaccines for protective efficacy in macaques

• Published in: Virology (New York, N.Y.) N.Y.), 2008-05, Vol.374 (2), p.528-534
• Main Authors: Kent, Stephen J, De Rose, Robert, Mokhonov, Vlad V, Mokhonova, Ekaterina I, Fernandez, Caroline S, Alcantara, Sheilajen, Rollman, Erik, Mason, Rosemarie D, Loh, Liyen, Peut, Viv, Reece, Jeanette C, Wang, Xiang Ju, Wilson, Kim M, Suhrbier, Andreas, Khromykh, Alexander
• Format: Article
• Language: English
• Subjects: AIDS Vaccines; Animals; Antibodies, Viral - blood; Flavivirus; Fusion Proteins, gag-pol - genetics; Fusion Proteins, gag-pol - immunology; Fusion Proteins, gag-pol - metabolism; Genetic Engineering; HIV; HIV-1 - genetics; HIV-1 - immunology; HIV-1 - metabolism; Human immunodeficiency virus; Infectious Disease; Kunjin; Lymphocyte Activation; Macaca; Macaca nemestrina; Macaques; Replicon; SAIDS Vaccines - administration & dosage; SAIDS Vaccines - genetics; SAIDS Vaccines - immunology; Simian Acquired Immunodeficiency Syndrome - immunology; Simian Acquired Immunodeficiency Syndrome - prevention & control; Simian Acquired Immunodeficiency Syndrome - virology; Simian immunodeficiency virus; Simian Immunodeficiency Virus - genetics; Simian Immunodeficiency Virus - immunology; Simian Immunodeficiency Virus - metabolism; Simian Immunodeficiency Virus - pathogenicity; SIV; T-Lymphocytes - immunology; Vaccines; Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology; Vaccines, Synthetic - metabolism; West Nile virus - genetics; West Nile virus - immunology; West Nile virus - metabolism
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2008.01.006

Abstract Persistent gag-specific T cell immunity would be a useful component of an effective HIV vaccine. The Flavivirus Kunjin replicon was previously engineered to persistently express HIV gag and was shown to induce protective responses in mice. We evaluated Kunjin replicon virus-like-particles expressing SIVgag–pol in pigtail macaques. Kunjin-specific antibodies were induced, but no SIV-specific T cell immunity were detected. Following SIVmac251 challenge, there was no difference in SIV viremia or retention of CD4 T cells between Kunjin–SIVgag–pol vaccine immunized animals and controls. An amnestic SIV gag-specific CD8 T cell response associated with control of viremia was observed in 1 of 6 immunized animals. Refinements of this vector system and optimization of the immunization doses, routes, and schedules are required prior to clinical trials.