PMID- 24456624 OWN - NLM STAT- MEDLINE DCOM- 20140816 LR - 20140203 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 32 IP - 9 DP - 2014 Feb 19 TI - Synthetic HIV-1 matrix protein p17-based AT20-KLH therapeutic immunization in HIV-1-infected patients receiving antiretroviral treatment: A phase I safety and immunogenicity study. PG - 1072-8 LID - S0264-410X(13)01794-5 [pii] LID - 10.1016/j.vaccine.2013.12.051 [doi] AB - BACKGROUND: Therapeutic vaccination is a promising novel approach to treat HIV-1 infected people by boosting or redirecting immune system to neutralize critical HIV-1 antigens whose biological effects are relevant in the context of viral pathogenesis. With the aim to induce neutralizing antibodies to the matrix protein p17 we have developed a peptide-based immunogen (AT20-KLH) and evaluated its safety and immunogenicity. METHODOLOGY: Twenty four asymptomatic HAART-treated HIV-1+ patients were enrolled in a phase I clinical study and were randomized to three groups: 2 groups were treated with five IM injection (Arm A: 25mug/inoculation; Arm B: 100mug/inoculation) at day (D) D0, D28, D56, D84 and D112; the control group (Arm C) were not injected. Safety was assessed by monitoring local and systemic adverse events (AEs), recorded till D168. Evaluation of immunogenicity was by titering antibodies at D0, D35, D56, D63, D84, D91, D112, D140 and D168 using ELISA. RESULTS: In all, 105 local and systemic AEs were reported across the three groups. Most were mild and resolved without sequelae. Also the few unsolicited events, deemed unrelated to the study vaccines, caused no problems. No significant changes in the routine laboratory parameters, CD4 T-cell count or HIV-1 viremia were found. At the time of enrollment 23 out of 24 patients had no anti-AT20 antibodies, whereas 11 exhibited anti-p17 antibodies. Irrespective of the presence of preimmunization antibodies, all subjects developed high titers of anti-AT20 antibodies (GM 9775) in response to both AT20-KLH doses. These antibodies were also capable of recognizing AT20 within the p17 framework. CONCLUSIONS: The AT20 peptide-based approach has allowed to redirect HAART-treated patients' humoral responses toward a previously untargeted hotspot of functional activity. Overall, the tested AT20-KLH doses were safe and well tolerated, supporting further exploration of AT20-KLH as an HIV-1 therapeutic vaccine candidate. CI - Copyright (c) 2013 Elsevier Ltd. All rights reserved. FAU - Iaria, Maria Luisa AU - Iaria ML AD - Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. FAU - Fiorentini, Simona AU - Fiorentini S AD - Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. FAU - Foca, Emanuele AU - Foca E AD - Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy. FAU - Zicari, Sonia AU - Zicari S AD - Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. FAU - Giagulli, Cinzia AU - Giagulli C AD - Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. FAU - Caccuri, Francesca AU - Caccuri F AD - Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. FAU - Francisci, Daniela AU - Francisci D AD - Section of Infectious Diseases, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, 06132 Perugia, Italy. FAU - Di Perri, Giovanni AU - Di Perri G AD - Department of Medical Sciences, University of Turin, Turin, Italy. FAU - Castelli, Francesco AU - Castelli F AD - Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy. FAU - Baldelli, Franco AU - Baldelli F AD - Section of Infectious Diseases, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, 06132 Perugia, Italy. FAU - Caruso, Arnaldo AU - Caruso A AD - Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. Electronic address: caruso@med.unibs.it. LA - eng PT - Clinical Trial, Phase I PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20140120 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (AIDS Vaccines) RN - 0 (Anti-Retroviral Agents) RN - 0 (Antibodies, Neutralizing) RN - 0 (HIV Antibodies) RN - 0 (HIV Antigens) RN - 0 (Vaccines, Synthetic) RN - 0 (gag Gene Products, Human Immunodeficiency Virus) RN - 0 (p17 protein, Human Immunodeficiency Virus Type 1) SB - IM MH - AIDS Vaccines/adverse effects/immunology/*therapeutic use MH - Adult MH - Anti-Retroviral Agents/therapeutic use MH - Antibodies, Neutralizing/blood MH - Antiretroviral Therapy, Highly Active MH - HIV Antibodies/blood MH - HIV Antigens/*immunology MH - HIV Infections/*therapy MH - HIV-1 MH - Humans MH - Immunity, Humoral MH - Middle Aged MH - Vaccines, Synthetic/adverse effects/immunology/therapeutic use MH - gag Gene Products, Human Immunodeficiency Virus/*immunology OTO - NOTNLM OT - HIV-1 matrix protein p17 OT - Peptide-based-immunotherapy OT - Therapeutic vaccine EDAT- 2014/01/25 06:00 MHDA- 2014/08/17 06:00 CRDT- 2014/01/25 06:00 PHST- 2013/07/09 00:00 [received] PHST- 2013/12/16 00:00 [revised] PHST- 2013/12/19 00:00 [accepted] PHST- 2014/01/25 06:00 [entrez] PHST- 2014/01/25 06:00 [pubmed] PHST- 2014/08/17 06:00 [medline] AID - S0264-410X(13)01794-5 [pii] AID - 10.1016/j.vaccine.2013.12.051 [doi] PST - ppublish SO - Vaccine. 2014 Feb 19;32(9):1072-8. doi: 10.1016/j.vaccine.2013.12.051. Epub 2014 Jan 20.