Community Advisory Group report by Simone Marcotullio
Barbara Ensoli from the National AIDS Centre in Rome, gave a comprehensive lecture on “Where we are in both vaccine fields: therapeutic and preventive”.
Preventive vaccines: Out of 42 candidates, only 8 are being tested in multiple phases and 2 in phase IIB. Interesting of note her approach on Tat-Delta V2 Env complex: a multicentric phase I open-label trial started one month ago with in 50 high risk individuals in Italy in cooperation with Novartis.
Therapeutic vaccines: 6 candidates are in early phases; Tat Italian strategy is the most advanced (phase II). Therapeutic approaches are important for sustaining and integrating ARVs for PLWHA.
Track A report by Scott G. Kitchen
The session TUSY01 “Preventative and Therapeutic HIV Vaccines: Novel Candidates and Strategies in 2011” highlighted some recent advances in HIV vaccine- related issues in the context of historical perspective. Overall, discussion highlighted the three major, recent vaccine trials: the AIDSVAX, STEP, and ALVAC/AIDSVAX trials and ways that the field is moving on from these studies, learning from both success and failures. Discussion also highlighted the need and importance for the generation of humoral and cellular immunity in an approach for a successful vaccine.
Dr. Barbara Ensoli began the discussion as co-chair of the session with a historical perspective/overview and highlighted the fact that there are currently 42 unique vaccine candidates under clinical development, none beyond Phase IIb. There are several promising preventative and therapeutic candidates in the pipeline that were discussed; and she highlighted her own recent work in the utilization of a vaccine involving a combination of HIV Tat and Env being efficacious in protecting macaques from mucosal SHIV challenge.
Dr. Susan Zolla-Pazner then discussed her work in the development of a “Structural Vaccinology Approach”, which involves the rational design of immunogens that can focus the immune response, particularly neutralizing monoclonal antibodies, on specific epitopes of HIV. She demonstrates the success in this approach in inducing cross-clade neutralizing antibodies using a gp120 DNA-based prime followed by a boost with a Env V3 attached to a Cholera Toxin B protein scaffold immunogen.
Dr. Susan Barnet provided an overview of results from the RV144 trial and other studies utilizing non-human primates, which suggest that vaccine protection from HIV is an achievable goal. The protection seen in these studies can be attributed to the ability of the vaccine candidate to elicit high aviditiy, high titer, Env targeting neutralizing antibodies. The ongoing goal is to identify a candidate that will provide this type of protection in humans.
Dr. David Weiner discussed significant advances in the development of DNA based vaccines and has identified an “enhanced” DNA vaccine candidate. When the DNA containing consensus sequences of the target antigen is combined with better delivery methods, such as tissue electroporation, and an IL-12 adjuvant, the DNA vaccine is capable of eliciting robust levels of cellular immune responses in HIV naïve people. This is the first demonstration of a significant positive effect of a DNA-based vaccine in humans in eliciting immunity.
Dr. Felipe Garcia highlighted past clinical trails and recent advances in dendritic cell based vaccine strategies. He emphasized the fact that the success of dendritic cell based vaccines has and is dependent on a number of variables and that a recent trial has demonstrated the ability of a dendritic cell based vaccine to elicit HIV-specific responses and reduction in viral load in a limited number of individuals.
In all, the session highlighted past acheivement and failures and the necessity for further development of rational HIV vaccine candidates that are capable of eliciting potent antiviral immune responses.