The afternoon session of Day One at the World Vaccine Congress USA 2013 got underway, with Dr Rick King, VP Vaccine Design at IAVI, chairing the session. He spoke about the hope and excitement surrounding broadly neutralizing antibodies, and introduced the first speaker for the session on HIV vaccines – Mitchell Warren, Executive Director at AVAC, who spoke about ‘creating sustained funding for HIV vaccine development’. In this presentation, Mr Warren spoke about the role of AVAC as an advocacy organisation, and introduced the concept of an AIDS-free generation – something which President Barack Obama had once stated as being within our reach. He spoke about the importance of ‘minding our language’ when discussing phrases like ‘end of epidemic’, ‘AIDS-free generation’, and ‘cure’. He gave an overview of all the HIV vaccine clinical trial milestones, including the results of AIDSVax in 2003, Merck Ad5 in 2007, and the hope conferred by the results of the 2009 RV144 trial in Thailand that showed benefit. He spoke about the hopes in 2006 – which included RV144, Merck Ad5, and PAVE 100 – and compared these to the realities in 2013 to show that the current vaccine landscape is now very different. He discussed the role of vaccination as part of a larger HIV prevention landscape that includes prophylaxis, microbicides, vaginal rings with antiretrovirals, and long-acting injectables. He spoke about HIV vaccine funding allocations from 2000-2011, and gave a list of the top HIV vaccine funders. He then went on to discuss the future of HIV vaccines, a list that includes the P5 (Pox-Protein Public-Private Partnerships), replicating vectors, translating Nab discoveries into vaccine candidates, and passive immunization. He discussed the preventive HIV vaccine clinical trial pipeline and the wide variety of pipeline approaches.
Dr Susan Barnett, Senior Project Leader, Senior Director, Vaccine Research at Novartis Vaccines & Diagnostics, spoke about a ‘Novel approach to HIV vaccine design’. She discussed two main topics – where are we now with HIV vaccines?; and where are we going in the future? She reiterated the hint of success with RV144 Thai trial that showed 31% efficacy – although the clinical efficacy had waned over time from 60%. She spoke about the P5 partnership established in 2010 to build on the RV144 results, with the aim to advance and license HIV pox-protein vaccine candidates, and she discussed the role of Novartis in the P5. She discussed the development of a vaccine using TV1 and 1086 gp120 monomers, and discussed the use of adjuvant formulations such as MF59, small molecule immune potentiators (SMIP), and TLR7 alum. She discussed a novel priming strategy using the newly-developed synthetic self-amplifying mRNA (SAM) vaccine platform to provide a non-viral vaccine delivery system. She spoke about SAM vaccines and how they work, and gave data on the use of an HIV-SAM vaccine expressing HIV-1 gp140.
Next to the stage was Dr Klaus Früh, Director, TomegaVax, Vaccine & Gene Therapy Institute, Oregon Health & Science University, who spoke about ‘Effector memory T cell-inducing persistent vaccine vectors’. Dr Früh explained how RhCMV/SIV vaccination can result in stringent, early control of highly pathogenic SIV challenge in monkeys, and continued to discuss the unique characteristics in CMV vector-mediated protection. What is so special about CMV vectors? Dr Früh explained that CMV vectors elicit high frequency effector memory T cells (that likely play the key role in controlling SIV), the unique ability of CMV to super-infect (and thus can use the vector in animals who already have SIV, and CMV can be used sequentially), the unusually and programmable T-cell targeting (the T cell response to CMV-vectored antigens is unusually broad), and the ability to maintain wild type-like persistent immunogenicity even when highly attenuated (and thus can develop safety-enhanced vectors as CMV causes many congenital defects and health issues in immunocompromised individuals).
To conclude the session on HIV vaccines, Dr Harriet Robinson, CSO at GeoVax, spoke about ‘DNA/MVA HIV vaccine, preclinical and clinical studies’. She discussed the results of a DNA prime, modified vaccinia Ankara (MVA) boost vaccine used in a serial challenge, rhesus macaque study. She continued to discuss the clinical trials with GeoVax DDMM and DgDgMM vaccines, and discussed results with the HTVN 205 DDMM regimen. Dr Robinson gave a schematic of the 2nd generation GeoVax DNA/MVA vaccine, which comprises DNA co-expressing GM-CSF and VLP (virus-like particles), and gave reasons for the use of GM-CSF in the vaccine.
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