Control of Viremia and Prevention of AIDS following Immunotherapy of SIV-Infected Macaques with Peptide-Pulsed Blood

PLoS Pathogens

Erik Rollman¹  Miranda Z. Smith¹  C. Jane Batten¹  Robert De Rose¹  Caroline S. Fernandez¹  Amanda J. Handley¹  Rosemarie D. Mason¹  Sheilajen Alcântara¹  Vivienne Peut¹  Liyen Loh¹  Matthew G. Law²  Kim Wilson³  Stephen J. Kent⁴ 

[1] Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia;National Centre for HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, New South Wales, Australia;National Serology Reference Laboratory, Fitzroy, Victoria, Australia;Opal Therapeutics Pty Ltd, Melbourne, Victoria, Australia

关键词: Macaque;    T cells;    SIV;    Immunotherapy;    Vaccination;    immunization;    Cytotoxic T cells;    Viremia;    Vaccines;   

DOI  :  10.1371/journal.ppat.1000055

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Effective immunotherapies for HIV are needed. Drug therapies are life-long with significant toxicities. Dendritic-cell based immunotherapy approaches are promising but impractical for widespread use. A simple immunotherapy, reinfusing fresh autologous blood cells exposed to overlapping SIV peptides for 1 hour ex vivo, was assessed for the control of SIVmac251 replication in 36 pigtail macaques. An initial set of four immunizations was administered under antiretroviral cover and a booster set of three immunizations administered 6 months later. Vaccinated animals were randomized to receive Gag peptides alone or peptides spanning all nine SIV proteins. High-level, SIV-specific CD4 and CD8 T-cell immunity was induced following immunization, both during antiretroviral cover and without. Virus levels were durably ∼10-fold lower for 1 year in immunized animals compared to controls, and a significant delay in AIDS-related mortality resulted. Broader immunity resulted following immunizations with peptides spanning all nine SIV proteins, but the responses to Gag were weaker in comparison to animals only immunized with Gag. No difference in viral outcome occurred in animals immunized with all SIV proteins compared to animals immunized against Gag alone. Peptide-pulsed blood cells are an immunogenic and effective immunotherapy in SIV-infected macaques. Our results suggest Gag alone is an effective antigen for T-cell immunotherapy. Fresh blood cells pulsed with overlapping Gag peptides is proceeding into trials in HIV-infected humans.

【 授权许可】

CC BY