HIV remains a serious health threat worldwide with millions of new cases every year. Anti-retroviral treatment has contained HIV spread in the Western world, but it is not curative and its high cost prohibits worldwide administration. So far, efforts to design and implement new vaccine strategies against HIV have failed mainly due to viral diversity. It is of critical importance to develop safe, effective and easily administrated vaccines. Scientific partners of the EU-funded CUT'HIVAC (Cutaneous and mucosal HIV vaccination) initiative set out to develop a needle-free vaccination approach against HIV. This would be highly advantageous compared to conventional immunisation techniques, considering that HIV endemic areas suffer from poor accessibility to drugs and sanitary conditions. Cutaneous and mucosal vaccination has provided novel insight on immune responses to vaccines, underscoring the role of antigen-presenting cells (APCs) in immunity. APCs initiate, maintain and regulate adaptive immune responses, comprising key targets in rational vaccine design. While cytotoxic effector T cells are required to control viral dissemination, the presence of anti-HIV neutralising antibodies at the site of viral entry is also important. CUT'HIVAC partners designed and developed a number of innovative HIV vaccine candidates based on murine leukaemia virus-like particles (VLPs). VLPs offer the unique advantage of displaying heterologous antigens, including HIV envelope glycoproteins, in their native conformation that is a pre-requisite for optimal neutralising antibody induction. Scientists investigated the immunogenicity of these vaccines in murine models and defined the early in vivo mechanisms. Furthermore, they conducted 4 phase I clinical trials to test the prophylactic and therapeutic capacity of DNA and MVA-HIV vaccine applied by various routes including transcutaneous needle-free administration. A start-up company was launched from CUT'HIVAC to develop and manufacture biodegradable particles that could be exploited in vaccine applications. This technology is expected to find broader use for generating vaccines against other diseases, including tuberculosis and malaria.
HIV, vaccine, CUT'HIVAC, needle-free, antigen-presenting cell, virus-like particles