Maria Luisa Iaria1, Simona Fiorentini1, Emanuele Focà2, Sonia Zicari1, Cinzia Giagulli1, Francesca Caccuri1, Daniela Francisci3, Giovanni Di Perri4, Francesco Castelli2, Franco Baldelli3, Arnaldo Caruso5. 1. Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. 2. Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy. 3. Section of Infectious Diseases, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, 06132 Perugia, Italy. 4. Department of Medical Sciences, University of Turin, Turin, Italy. 5. Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. Electronic address: caruso@med.unibs.it.
Abstract
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: 25μg/inoculation; Arm B: 100μg/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.
RCT Entities:
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: 25μg/inoculation; Arm B: 100μg/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.
Authors: Francesca Caccuri; Serena Messali; Alberto Zani; Giovanni Campisi; Marta Giovanetti; Stefania Zanussi; Emanuela Vaccher; Silvia Fabris; Antonella Bugatti; Emanuele Focà; Francesco Castelli; Massimo Ciccozzi; Riccardo Dolcetti; Robert C Gallo; Arnaldo Caruso Journal: Proc Natl Acad Sci U S A Date: 2022-06-28 Impact factor: 12.779
Authors: Francesca Caccuri; Vera Neves; Arnaldo Caruso; Miguel Castanho; Lurdes Gano; João D G Correia; Maria Cristina Oliveira; Pietro Mazzuca Journal: J Virol Date: 2021-10-20 Impact factor: 6.549