Pox-Protein Public-Private Partnership (P5) Established in 2010 to build on the RV144 results Seeks to advance and ultimately license HIV pox-protein vaccine candidates that have the potential to achieve a broad public health impact The Phase III HIV Vaccine Trial, also known as RV144, was the largest HIV vaccine study ever conducted in humans and involved more than 16,000 volunteers in Thailand. The trial tested a “prime-boost” combination of two vaccines and provided first evidence that an HIV vaccine is possible

Strategy includes Licensure & Research Tracks LICENSURE TRIAL: Thailand Population: MSM, high-risk Products: ALVAC (Sanofi Pasteur) + gp120/adjuvant Partners/Funders: US Army, Thai Gov’t, NIH, Sanofi Pasteur, BMGF RV144 FOLLOW-UP: Thailand Research Studies: RV144i immune correlates studies RV305 protein boost -subset from RV144 RV306 expanded immunogenicity of RV144 regimen RV328 AIDSVAX B/E study Partners/Funders: US Army, Thai Gov’t, NIH, Sanofi Pasteur, BMGF LICENSURE TRIAL: South Africa Population: Heterosexual, high-risk Products: ALVAC (sanofi pasteur) + gp120/MF59 (Novartis) Partners/Funders: NIH, HVTN, Sanofi Pasteur, Novartis, BMGF RESEARCH TRIAL Population: Heterosexual, high-risk Products: DNA + NYVAC (sanofi pasteur) + protein/adjuvant (such as MF59) versus NYVAC (sanofi pasteur) + protein/adjuvant Ad26/MVA Partners/Funders: NIH, HVTN, Sanofi Pasteur, Novartis, BMGF

Next Steps The P5 has initiated the multi-step development process for vaccine components: Includes vector and immunogen development activities, production of clinical lots, preclinical studies and safety characterizations P5 is concurrently working on: Regulatory planning and access agreements Collaborating with government and communities within the host countries

Scientific Objective of Phase 1-2 Trial in Southern Africa To demonstrate immune responses from clade C vaccine sufficient to extend results of RV144 vaccine To determine if levels of V1V2 antibody responses to clade C vaccine will enable testing of the V1V2 hypothesis as a vaccine-induced Correlate of Protection (CoP)

SOUTHERN AFRICAN COUNTRIES Total: 6 N# OF SITES Total: 30 South Africa 20 Mocambique 2 Botswana Zimbabwe 3 Zambia Malawi HIV incidence in South African women: 3.5-9% men: 2.2-3.7% G. Gray

Cape Town HIV Vaccine Laboratory: ~10,000 ft2 Facility Stronger lab infrastructure is needed in-country to support these large-scale studies, particularly for conducting cellular endpoint analyses and exploratory mucosal studies. The Cape Town laboratory will open in July 2013, with funding from: BMGF- $3 million for renovations of the space and lab equipment NIH/DAIDS (HVTN grant)- additional equipment and operating budget Aeras- agreement under negotiation to share space and expenses Laboratory projects: Phase I -Investigate cellular endpoint studies in vaccine trials. -Establish training center for young laboratory investigators and laboratory staff involved in South African clinical trials. Phase II -Support combination HIV prevention and non-HIV vaccine studies in Southern/Eastern Africa. -Facilitate career development of lab scientists who can assume future leadership roles in infectious disease clinical research. J McElrath