I’m pleased to share our new edition of Vaccines for the Future, which captures updates from across PATH’s Vaccine Development Program (VAC). Earlier this month, we gathered most of the VAC team together for our annual program review meeting in Seattle, where we exchanged updates on various projects, partnerships, clinical trials, and supporting research. It was great for everyone to learn more about each other’s work, and for the team to work together to find solutions to some of the common challenges we face. We currently have more than 25 active partnerships with external collaborators around the world, including several new ones highlighted in this newsletter. Since VAC began in 2006, we have completed seven clinical trials, with nine more currently ongoing, and another ten slated to launch within the next year. While we are pleased with our progress, we have much more to do in order to accomplish all of our goals.

John W. Boslego, MD
Director, Vaccine Development Program
PATH

PATH recently established separate collaborations with GlaxoSmithKline Vaccines and Novartis Vaccines & Diagnostics, Inc., to develop respiratory syncytial virus (RSV) preclinical models for evaluating vaccine candidates for pregnant women. These studies will include in vivo and in vitro models designed to add to the RSV vaccine development toolbox. In another new research collaboration, PATH and Dr. Janet Englund of Seattle Children’s Research Institute are studying RSV disease burden as well as the transfer and protective effect of maternal-derived RSV antibody in infants in Bangladesh and Nepal. These new partnerships will support the efforts of PATH’s RSV vaccine pilot project to evaluate feasibility for a maternal immunization strategy to protect children in the earliest months of life from RSV.

In other news, PATH co-sponsored the Eighth International Respiratory Syncytial Virus Symposium from September 27 to 30, 2012 in Santa Fe, New Mexico. Dr. Kathleen Neuzil, Director of Vaccine Access and Delivery at PATH, presented on the promise and challenge of a maternal immunization approach to RSV prevention in low-resource countries. Deborah Higgins and Cheryl Keech of PATH’s RSV pilot project also attended the conference and hosted a side meeting with representatives from seven of the project’s partners.

PATH has begun working with Beijing Tiantan Biological Products Co., Ltd. (TiantanBio) in China on improving manufacturing practices and capacity to increase the supply of affordable oral polio vaccine to UNICEF. Through the polio vaccine development and scale-up project, PATH is providing assistance in cell line and virus seed stock documentation, raw materials qualification, analytical test methods, quality management, and World Health Organization prequalification to TiantanBio. PATH is also advising Biological E. Limited in India on the company’s process optimization and scale up initiatives for enhancing its pentavalent vaccine capacity. The company’s pentavalent platform forms the basis of its long-term aim to develop a hexavalent combination vaccine (containing whole cell pertussis and inactivated polio vaccine). Finally, PATH is pleased to announce the formation of the project’s new scientific advisory board, which will hold its first meeting in November 2012.

PATH’s non-replicating rotavirus vaccine project marked achievements in the development of its three vaccine candidates. A Good Laboratory Practices toxicity study in preparation for a first-in-man Phase 1 trial of the V2-P8 candidate found no unexpected adverse events and confirmed immunogenicity of the vaccine formulation to be administered in the Phase 1 study. To manufacture and evaluate the P particle-VP8 candidate, PATH negotiated a non-exclusive, royalty-free license for developing countries, excluding China, from Cincinnati Children’s Hospital Medical Center. Finally, PATH and Serum Institute of India, Ltd. negotiated a research agreement for the development of a chemically inactivated whole virus vaccine candidate.

PATH’s enteric vaccine project recently obtained results from a Phase 1 trial of an oral, live attenuated Shigella vaccine candidate, CVD1208S, developed by the Center for Vaccine Development (CVD) at the University of Maryland. PATH and CVD previously tested the vaccine in a Phase 2 trial that was halted because a small number of participants experienced adverse reactions to the vaccine. This new study followed a carefully controlled dose-escalation regimen and used a new vaccine lot prepared under Good Manufacturing Practices. Results from the first two cohorts indicate that CVD1208S has been significantly improved through the formulation work PATH supported. No adverse events were identified and the immune response was robust. PATH’s support to the study has ended, but CVD may pursue further clinical evaluation of CVD1208S.

In follow up to a successful inaugural meeting last year, PATH sponsored the Development of Pneumococcal Conjugate Vaccines, Part II symposium from October 17 to 19 in Beijing, China, which brought together nearly 50 international experts and scientific staff of potential Chinese pneumococcal conjugate vaccine (PCV) manufacturers. The participants shared their knowledge and experience in order to accelerate the development of PCVs in emerging markets, including China. The focus of this year’s meeting was on clinical and regulatory late-stage development of PCVs. From PATH’s pneumococcal vaccine project team, Drs. Mark Alderson and Jeff Maisonneuve delivered opening remarks and presentations. Overall, the information exchanged at the symposium helped advance larger efforts by PATH and other global health organizations to foster competitive markets that include emerging-country manufacturers like those in China—a critical strategy for making lifesaving vaccines such as PCVs sustainably affordable, available, and accessible for low-resource countries.

September 2012:

• A Phase 1 trial of the live attenuated ACE527 vaccine against enterotoxigenic Escherichia coli, combined with the experimental adjuvant dmLT (double-mutant heat-labile toxin), launched in Baltimore, Maryland. The study aims to evaluate the safety and immunogenicity of a new formulation of ACE527, with and without dmLT, in a three-dose regimen in 60 healthy adults.

October 2012:

• A Phase 1 trial of a live attenuated influenza A/H5N2 vaccine candidate launched in St. Petersburg, Russia, and is enrolling 40 healthy adults 18 through 49 years of age.
• A Phase 2 trial of an RSV fusion (F) protein nanoparticle vaccine candidate launched in four clinical trial sites in the United States and is enrolling 330 healthy, non-pregnant women of childbearing age between 18 and 35 years old.

Since 2009, PATH has been the lead partner in the Accelerated Vaccine Introduction (AVI) initiative Technical Assistance Consortium (AVI TAC), which is funded by the GAVI Alliance and is focused on accelerating access to and sustaining the introduction of new vaccines in low-income countries. A primary emphasis of PATH’s AVI TAC work includes providing technical, scientific, advocacy, and communication expertise, tools, and evidence to support the introduction of rotavirus vaccines in countries where the burden of disease is high and children need them most urgently.

At the International Rotavirus Symposium in Bangkok in September, PATH AVI presented pivotal new data on rotavirus vaccine efficacy in Bangladesh, and Dr. Kathleen Neuzil, Director of Vaccine Access and Delivery at PATH and Director of AVI TAC, co-moderated a session on the importance of advocacy in vaccine introduction. In addition, PATH AVI recently launched a new rotavirus vaccine access and delivery website, which includes facts about rotavirus disease and vaccines, details about PATH’s approach, an advocacy and communications toolkit, and many other resources. These efforts complement VAC’s work on developing new live attenuated and non-replicating rotavirus vaccine candidates, with PATH AVI laying critical groundwork for generating demand for rotavirus vaccines in low-resource settings.