Potentiating Host Immunity for HIV-1 Functional Cure

Abstract

HIV/AIDS has been a major health burden worldwide, with more than 39.0 million people living with HIV-1 (PLWH) currently. In Hong Kong, there are more than 11943 accumulative cases reported in total nowadays. Although combined anti-retroviral therapy (cART) is available, this life-long treatment is expensive and may cause adverse effects or drug resistance in PLWH. This TRS project aims to develop a promising immunotherapeutic strategy to suppress HIV-1 infection to undetectable viremia levels in PLWH without life-long cART.

Our research team has set up collaborations with two biomedical companies for the manufacture of Good Laboratory Practice/ Good Manufacturing Practice (GLP/GMP)-graded PD-1-based DNA vaccine (ICVAX vaccine) and bi-specific antibody (BiIA-SG). The preventive or protective efficacies against AIDS, as well as their underlying mechanisms, were tested in the SHIV-infected rhesus macaque model. Collectively, both immunotherapeutic strategies work efficiently and effectively in prophylactic administration at the pre-exposure and/or post-exposure of viral infection. After obtaining various approvals of GMP, Investigational new drug (IND), research ethics, etc., we successfully brought the ICVAX vaccine into Phase I clinical trial. Our 5-year TRS project illustrated the translational process of our scientific discoveries into clinical development. It leads a promising “made in Hong Kong” immunotherapeutic candidate to the future hope of local and international AIDS communities.

Research Impact

Our overall objective is to potentiate host immunity to achieve a functional cure for HIV-1 infection, a status of suppressed viremia below the limit of detection, for benefiting PLWH without receiving ART. First, our research team successfully brought the ICVAX vaccine into Phase I clinical trial and illustrated the translational process and the underlying mechanisms of our scientific discoveries into clinical development step by step. It leads to a promising “made in Hong Kong” immunotherapeutic candidate for the functional cure of AIDS. Second, by establishing a Hong Kong consortium of outstanding scientists and biomedical R&D companies, we generated GLP/GMP-grade vaccines or antibodies for preclinical and clinical studies. We also developed the PD-1-based vaccination platform not only in the field of HIV/AIDS, but also in other diseases such as COVID-19 and cancer with 2 patents granted and 1 patent filed. Third, we generated 20 peer-reviewed publications in leading scientific journals and 17 international conference papers during this project period. Moreover, we have obtained research grants from other sources to work on 4 new projects, which evolved directly from this TRS project. These projects further promote our future biomedical research and drug development in the area of infectious diseases.