Vaccines for the Future: News from PATH's Vaccine Development Program

April 2010

In this issue:

Welcome to the latest edition of Vaccines for the Future. With this issue we are pleased to announce new funding to expand PATH's work on diarrheal disease, as well as several new partnerships to advance vaccines against enterotoxigenic Escherichia coli and pneumococcus. We also include updates from several current partnerships, a recap of our participation in a premier international pneumococcal conference, and an overview of a recent meeting with top Vietnamese health officials on influenza vaccine production.

In addition, we highlight the Global Health Technologies Coalition, an alliance of organizations advocating for investment in health product research, for which PATH serves as the secretariat. We also link to new PATH resources, list upcoming conferences and events, and link to job opportunities at PATH. As always, we welcome your feedback and hope these updates continue to be useful.

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

PATH receives new funding for the development of vaccines against diarrheal disease

The United Kingdom's Department for International Development recently announced that it will provide funding to PATH to expand research and development of vaccines to address diarrheal disease. The five-year, £5 million grant will support PATH's work to advance the development of new, safe, effective, and affordable vaccines against rotavirus, Shigella, and enterotoxigenic Escherichia coli (ETEC). While two licensed vaccines against rotavirus currently exist, additional products are needed to ensure a robust supply and lower prices for the developing world. There are no licensed vaccines available today to address Shigella or ETEC. Accelerating the development of vaccines is one aspect of PATH's multifaceted approach to protecting young children from diarrheal disease. PATH also works with countries and communities on strategies to increase the use of currently available treatment and prevention interventions, such as oral rehydration solution, zinc, exclusive breastfeeding, improved hygiene and sanitation practices, and increased access to safe water.

Research projects advance rotavirus vaccine efforts

As several emerging-country manufacturers pursue development of a bovine-human reassortant vaccine, PATH is developing technologies, training, and materials to support the manufacturers' vaccine development efforts. Since 2007, PATH's rotavirus vaccine development project has been working with Aridis Pharmaceuticals to develop a fully liquid rotavirus vaccine formulation. After investigating more than 30 initial formulations, Aridis selected and optimized five. Based on composition and stability data, PATH selected two of these five formulations. PATH's Technology Solutions team made additional improvements in fluidity, dissolvability, and buffering capacity to the two formulations. PATH has provided the composition of these two formulations to the manufacturers and will continue to provide technical support to help the manufacturers implementing these formulations at pilot scale should they elect to do so.

PATH continues its work with Bharat Biotech International on the 116E rotavirus vaccine candidate as the partners prepare for a Phase 3 clinical trial later this year. As part of due diligence, PATH conducted an assessment of the cold chain capacity in India to support the storage of a new rotavirus vaccine that would become part of the Indian universal immunization program. The report looked at the ability of the cold chain system in the country to accommodate the first-generation 116E vaccine, which will need to be kept frozen at -20° Celsius. The assessment encompassed current cold chain volume, the proposed 116E vaccine and antacid presentation, the estimated demand and uptake of the rotavirus vaccine based on current coverage of the other Expanded Program on Immunization vaccines, and rollout patterns for new vaccines. It concluded that there would be enough capacity in the -20°C cold chain in India to accommodate 116E vaccine introduction.

New research partnership on novel approach to ETEC vaccine

PATH is partnering with the International Enteric Vaccine Consortium (ENTVAC) on early-stage research into a vaccine concept against ETEC. PATH, as part of its enteric vaccine initiative, will provide funding of $1.1 million over 2.5 years to ENTVAC, a consortium of universities anchored by the University of Maryland School of Medicine to pursue preclinical proof of concept of a stable toxin (ST) toxoid vaccine. Such a vaccine offers the prospect of broad protection against ETEC, but requires additional research and evaluation. Epidemiologic studies strongly suggest that ETEC strains that release ST contribute significantly to disease burden, causing the most common and serious infections. While exposure to other ETEC strains can lead to immunity, children can experience many symptomatic infections with an ST-producing strain. The ability to induce protective antibodies to ST could be an important public health goal, but it has heretofore proved elusive. The project aims to identify one or more ST clones that are safe and immunogenic.

Investigators stop trial of Shigella vaccine

PATH and the Center for Vaccine Development (CVD), University of Maryland, Baltimore, halted a Phase 2 clinical trial of a vaccine candidate for Shigella flexneri (CVD 1208S) in mid-February 2010, after a small number of study volunteers experienced adverse events (fever, abdominal cramping, and loose stools). The vaccine had been shown to be safe in previous human trials, and the trial had been approved by the US Food and Drug Administration (FDA) and multiple institutional review boards. Since the use of a new medium for growing the vaccine inoculum may have affected the clinical tolerability of the vaccine, CVD will conduct a number of studies to compare vaccine organisms grown in the new medium to organisms grown in the medium previously used in human trials. Based on those results, the partners will determine the next steps forward for this vaccine candidate.

Visit from top Vietnamese health officials builds dialogue on influenza vaccine production

PATH's Washington, DC, office recently welcomed senior officials from Vietnam's Ministry of Health for a series of meetings to foster communication on vaccine development and other health strategies in Vietnam. Three Vietnamese delegates, led by vice minister Dr. Nguyen Thi Kim Tien, spent a day with PATH staff to discuss developments from PATH's current projects in Vietnam, as well as other potential opportunities for collaboration. A major segment of the visit focused on reviewing plans for a project to support the enhancement of influenza vaccine production in Vietnam, which the Biomedical Advanced Research and Development Authority within the US Department of Health and Human Services recently awarded to PATH. Drs. Rick Bright and George Robertson of PATH met with the Vietnamese delegation to achieve early concurrence on the project strategy and to establish transparent and collaborative communication going forward. Other PATH staff engaged with the ministry on topics covering PATH’s various vaccine development projects, global health advocacy efforts, and activities beyond vaccine development.

PATH partnerships make strides to advance pneumococcal vaccine technologies

Intercell AG of Austria recently announced initial Phase 1 clinical trial results for IC47, its common protein vaccine candidate against Streptococcus pneumoniae. PATH, as part of its pneumococcal vaccine project, has partnered with Intercell since 2005 to support the preclinical and clinical development of IC47—a recombinant subunit vaccine candidate consisting of three conserved surface proteins from S. pneumoniae. During the first-in-human trial, investigators administered two different dosages of the vaccine candidate either with or without an aluminum hydroxide adjuvant to 32 healthy adults in Germany. Trial data showed the vaccine candidate to be safe, tolerable, and immunogenic among study participants. It also confirmed antigen dose-dependent induction of antibodies for all three proteins included in the vaccine candidate. While questions remain about how IC47 will perform in further clinical evaluations, if successful, the vaccine candidate could potentially offer broad, serotype-independent protection against pneumococcus, which kills nearly one million children under the age of five each year, mostly in the developing world.

PATH recently formed a new public-private partnership with the Center for Biologics Evaluation and Research within the FDA to optimize a key preclinical development step for pneumococcal conjugate vaccines (PCVs)—the conjugation process. The aim is to enhance the efficiency and cost-effectiveness of this process, which links polysaccharides with carrier proteins to strengthen a vaccine's immunogenicity, particularly in infants and children. This research collaboration will play a valuable role in supporting PATH's efforts to speed the development of novel and inherently affordable PCV candidates that are optimal for children in the developing world.

Premier conference features PATH's pneumococcal disease prevention work

PATH staff joined researchers and clinicians from around the world to review advances in the pneumococcal field at the Seventh International Symposium on Pneumococci and Pneumococcal Diseases from March 14 to 18, 2010, in Tel Aviv, Israel. As a co-sponsor, PATH helped bring into focus efforts to develop new, affordable vaccines against S. pneumoniae for children in the developing world. Generating notable interest were presentations by Intercell AG, Children's Hospital Boston, Genocea Biosciences, and GlaxoSmithKline Biologicals SA on their collaborative work with PATH to develop novel pneumococcal vaccines using protein technologies. Dr. Mark Alderson of PATH's pneumococcal vaccine project further highlighted PATH's vaccine development activities against pneumococcal disease at a luncheon session hosted by the Bill & Melinda Gates Foundation, while PATH's booth in the exhibition hall offered a one-stop-shop for interested attendees to access information and dialogue with PATH staff.

Changes in the pneumococcal vaccine landscape hold promise for developing countries

The FDA recently approved Pfizer's Prevnar 13™ PCV, which expands protection against 13 pneumococcal serotypes, some of which are prevalent in the developing world. The Advisory Committee on Immunization Practices within the US Centers for Disease Control and Prevention has recommended the vaccine for all children 2 through 59 months of age and for at-risk children 60 to 71 months of age with underlying medical conditions. In related news, the GAVI Alliance announced that Pfizer and GlaxoSmithKline recently signed the first-ever agreements under the Advance Market Commitment (AMC)—a financing mechanism designed to incentivize manufacturers to supply vaccines for low-income nations at a fraction of the price paid by wealthier countries. Each company will supply 30 million cut-price PCV doses per year over ten years for developing countries. AMC funds and the GAVI Alliance will split the $7.00 price per dose for the first 20 percent of vaccines supplied, with co-pays from developing countries as low as $0.15 per dose. The GAVI Alliance will pay a reduced price of $3.50 per dose to cover the cost of the remaining 80 percent. PCVs are some of the most effective tools available today for reducing severe pneumonia and other illnesses caused by S. pneumoniae, but they are also complex and relatively expensive to manufacture. The AMC is an important step toward making these vaccines accessible for low-resource countries in the short- to medium-term, while researchers continue longer-term efforts to develop new, simpler vaccines that low-resource countries can afford without assistance.

Also@PATH: Working in coalition for policies to accelerate global health research and development

PATH serves as the secretariat for the Global Health Technologies Coalition (GHTC), an alliance of more than 30 organizations advocating for critical investment in research into health products—such as drugs, vaccines, diagnostics, and other devices—for the developing world. On April 21, 2010, GHTC hosted its first annual congressional expo on research and development for global health to showcase critical new tools under development for diseases that disproportionately burden low-income countries. The event also launched GHTC's first annual report, Innovation in action: policies to accelerate development and delivery of global health tools, which focuses on GHTC's three priority areas—US policies related to public financing, regulatory pathways, and incentives and innovating financing. It highlights the role US agencies and policymakers play in advancing innovation for global health products and outlines policy recommendations for Congress and the Obama Administration to help accelerate the development of much needed global health technologies.

Upcoming conferences and events

  • Parenteral Drug Association Vaccine Conference 2010, Bethesda, Maryland, May 17 to 20. This workshop will examine technical and regulatory challenges for the vaccine industry when developing high-quality vaccines under continued supply to global markets. Interactive session topics will include novel adjuvants, supply chain complexities, and requirement expansion for preclinical testing. PATH's Dr. John Boslego will speak during the open plenary session on "NGOs and Vaccines Beyond US Borders: Vaccines to Support the Developing World."
  • Vaccine Technology III, Nuevo Vallarta, Mexico, June 6 to 11. This conference brings together key leaders from academia, industry, and government to share the latest developments in vaccine technology with a particular focus on the special challenges for emerging markets and the developing world. This year's topics include vaccines in late-stage development, new technologies, technology challenges in the developing-world markets, progress in key developing-world regions, and many more. Dr. Boslego will present on "New vaccine technologies: Promising advances may save more lives."
  • Global Health Council's 37th Annual International Conference on Global Health, Washington, DC, June 14 to 18. This year's conference, Dateline 2010: Global Health Goals & Metrics, will focus on metrics, progress, and challenges related to global health goals, including the Millennium Development Goals. The conference brings together more than 2,500 practitioners, global health and world leaders, activists, multilateral organizations, researchers, and others to discuss key global health topics. In addition to hosting a booth in the exhibition hall, several PATH staff will present and moderate sessions at the conference.
  • Development of Strategies to Overcome Barriers to Effective Mucosal Immunization of Infants in Developing Countries, Herborn, Germany, June 24 to 25. This workshop, co-sponsored by PATH, will convene experts in vaccination, mucosal immunization, and intestinal microflora to discuss impaired mucosal immune regulation, which has been a roadblock to fully successful oral immunization of infants and children in developing countries. Dr. Dick Walker of PATH's enteric vaccine project is co-chairing the meeting.
  • 7th International Conference on Emerging Infectious Diseases, Atlanta, GA, July 11 to 14. This annual conference brings together epidemiologists, laboratory scientists, public health practitioners, and others to exchange scientific and public health information on global emerging infectious disease issues. Dr. Boslego will present on new vaccine development. Other session topics will include antimicrobial resistance, foodborne and waterborne illnesses, global health, and more.

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New PATH resources

PATH recently launched a new website, DefeatDD.org, aimed at providing tools to inform and inspire advocates committed to joining their voices and raising awareness about diarrheal disease. The website provides key documents and links to information on simple, lifesaving interventions that have the potential to significantly impact diarrhea incidence worldwide. You can also keep up-to-date on the latest diarrheal disease information by following the DefeatDD team on Twitter or by signing up for the e-newsletter, 3D News!

In addition, several new fact sheets on PATH's pneumococcal and influenza vaccine projects are now available.

Job opportunities

PATH's vaccine development program has several open positions listed below. Please visit the employment opportunity web page for all open PATH positions.

View past issues of Vaccines for the Future

PATH's vaccine development program is working to accelerate the development of innovative, safe, effective, and affordable vaccines against the leading causes of childhood deaths in the developing world, pneumonia (pneumococcal disease) and diarrheal disease (rotavirus, Shigella, and enterotoxigenic Escherichia coli), as well as new influenza vaccines for the global population. PATH is also partnering on vaccine development through its Malaria Vaccine Initiative and the Meningitis Vaccine Program. Additionally, PATH works to ensure the worldwide availability of vaccines through its Vaccine Access and Delivery Program. The work of the vaccine development program is currently supported by grants from the Bill & Melinda Gates Foundation and the US Centers for Disease Control and Prevention. Some projects within the vaccine development program are funded by PATH Vaccine Solutions.

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