July 2009

In this issue:

• Phase 1 trial begins for enterotoxigenic Escherichia coli vaccine candidate
• PATH forges new influenza vaccine research partnerships
• Africa’s largest influenza vaccine trial to date launched by PATH and partners
• PATH enters into new collaborations to develop low-cost pneumococcal vaccines
• The world’s first Advance Market Commitment kicks off to support global access to pneumococcal vaccines
• New rotavirus vaccine candidate moves closer to clinical trials
• Stalled progress on a leading childhood killer spurs report and Call to Action
• Journal article highlights the need for vaccination against deadly diarrheal disease in Africa
• Vaccine Resource Library highlights
• Upcoming conferences and events

Welcome to the latest edition of Vaccines for the Future. This issue highlights several new milestones for our program, including the launch of two clinical trials and the addition of several new partnerships. A Phase 1 trial for an enterotoxigenic Escherichia coli vaccine candidate began in June, while Africa’s largest influenza vaccine trial was launched in May. We have also added new partnerships to our pneumococcal and influenza vaccine development projects. In addition, we share the launch of the inaugural Advance Market Commitment, which is focused on increasing access to vaccines against pneumococcal disease.

Finally, we feature several new resources, including a PATH report and Call to Action on diarrheal disease and exciting additions to the Vaccine Resource Library. We also share a journal article on cholera in Africa to which members of our staff contributed. As always, we hope these updates continue to be useful, and we welcome your feedback.

Sincerely,

John W. Boslego, MD

Director, Vaccine Development Program

PATH

Phase 1 trial begins for enterotoxigenic Escherichia coli vaccine candidate

PATH supported the June launch of a Phase 1 clinical trial of an oral enterotoxigenic Escherichia coli (ETEC) vaccine candidate with partner ACE BioSciences, a vaccine company based in Denmark. The trial, which is taking place in Baltimore, Maryland, at the Center for Immunization Research at Johns Hopkins University, will test the safety and immunogenicity of ACE527, a live attenuated, whole cell vaccine which is comprised of three ETEC strains and should provide broad coverage. Researchers are enrolling 36 healthy adult volunteers in the study and will administer two vaccine candidate doses to each participant, either at a high or low dose level. The trial is expected to be completed by September 2009 with results available by December 2009.

PATH’s enteric vaccine development project also supported the recent Good Manufacturing Practices production of double mutant heat-labile toxin (dmLT) adjuvant at the Walter Reed Army Institute of Research’s Pilot Bioproduction Facility in Silver Spring, Maryland. The dmLT, a highly promising new adjuvant that PATH in-licensed from Tulane University, is also an ETEC antigen that may offer protection against disease. The newly produced vials of dmLT will next go through lot release tests, and then a formal Good Laboratory Practices toxicity study later this year. All of these efforts are in preparation for a planned Phase 1 clinical trial of dmLT, expected to begin in 2010.

PATH forges new influenza vaccine research partnerships

As part of its influenza vaccine project, PATH recently entered into two new research collaborations to support its strategy of increasing developing world access to affordable influenza vaccines. In the first partnership, the Midwest Research Institute of Kansas City, Missouri, will serve as the primary preclinical facility performing immunogenicity, challenge, and toxicology studies, as well as associated assays for PATH’s influenza vaccine partners. The second collaboration teams PATH with Neugenesis Corporation (PDF) of Burlingame, California, to conduct feasibility studies on an influenza vaccine production system from the transformed filamentous fungus Neurospora crassa, which can be used to make virus-like particles.

Africa’s largest influenza vaccine trial to date launched by PATH and partners

PATH’s vaccine development program, in collaboration with the Institut de Recherche pour le Développement and the Institut Pasteur de Dakar, recently launched a large-scale, cluster-randomized trial funded by the US Centers for Disease Control and Prevention to evaluate the effectiveness of inactivated influenza vaccine among children in Senegal. In May and June, nearly 8,000 children six months to ten years of age in the Fatick District of Senegal were enrolled and vaccinated as part of the study, making it the largest influenza vaccine trial ever conducted in Africa. Enrolled children received either a licensed trivalent influenza vaccine or a beneficial control vaccine—inactivated polio vaccine.

In the upcoming months, investigators will conduct passive and active surveillance to identify influenza among participants and in their communities. In addition to evaluating the protection afforded to vaccinated children, investigators will evaluate the extent to which immunizing only children, the suspected main transmitters of influenza, effectively reduces disease in the rest of the community. Such information will help national and global public health officials understand how to most appropriately use influenza vaccines in Africa. By utilizing active surveillance in a demographically well-defined population, the study will also enable the calculation of influenza rates to help define the burden of influenza, something almost totally unknown in tropical regions of Africa, as well as help strengthen Senegal’s already exemplary national influenza surveillance program.

PATH enters into new collaborations to develop low-cost pneumococcal vaccines

PATH’s pneumococcal vaccine project recently signed separate agreements with vaccine producers Serum Institute of India Ltd. and China National Biotec Group’s Chengdu Institute of Biological Products to speed the development of affordable pneumococcal conjugate vaccines (PCVs) against Streptococcus pneumoniae that are optimal for use in low-resource countries. PCVs couple the polysaccharide capsule of pneumococcal serotypes with carrier proteins to make them immunogenic in infants and toddlers. These PCVs will target the seven or eight strains most prevalent in Asia and Africa, which cause more than 60 percent of invasive disease in children under five years old. By producing vaccines in India and China, PATH aims to reduce manufacturing costs to ultimately meet technical and pricing requirements for Advance Market Commitments through the GAVI Alliance and World Bank. The strategy is to combine proven conjugation methods with new technologies for rapid and cost-effective vaccine development. To support the China work, PATH is also partnering with South Africa’s Biovac Institute to provide technical expertise.

The world’s first Advance Market Commitment kicks off to support global access to pneumococcal vaccines

In June, global health partners announced the launch of the first-ever Advance Market Commitment (AMC), which will speed the availability of vaccines against Streptococcus pneumoniae for 60 of the world’s lowest-income countries by 2015. The initiative is an important step toward reducing the traditional 15- to 20-year lag between the introduction of new vaccines in wealthy countries and their availability in the developing world. Sponsors estimate the effort could help save the lives of more than seven million children from pneumococcal disease by 2030. Under the AMC, donors commit funds to guarantee the price of future vaccines, creating incentives for producers and catalyzing competition on supplying vaccines at long-term lower prices. As a result, low-resource countries will be able to access critical pneumococcal vaccines for US$3.50 per dose instead of the current cost of US$70. Over the next six years, the Bill & Melinda Gates Foundation and the governments of Italy, the United Kingdom, Canada, Russia, and Norway are funding the AMC pilot for a total of US$1.5 billion and the GAVI Alliance has committed US$1.3 billion. Other key partners include the World Bank for fiduciary support, UNICEF for vaccine procurement and distribution, and the World Health Organization for ensuring that all pneumococcal vaccines developed through an AMC comply with technical standards.

New rotavirus vaccine candidate moves closer to clinical trials

PATH supported the recent production of clinical trial lots of the RV3 rotavirus vaccine candidate, which is being developed by Murdoch Childrens Research Institute (MCRI) in Australia. MCRI contracted Meridian Life Science, Inc. in Memphis, Tennessee, to manufacture the candidate according to appropriate current Good Manufacturing Practices for their upcoming Phase 1 and 2 clinical trials. The Phase 1 trial is expected to begin in the fourth quarter of 2009 in Australia. PATH is also involved in the development of RV3 through participation in its vaccine advisory committee. Dr. Duncan Steele, a senior technical officer at PATH, is a member of the RV3 vaccine advisory committee and chaired their most recent meeting on June 30. Dr. Georges Thiry, director of PATH’s rotavirus vaccine development project, also participated in the meeting as an observer. The meeting was followed by a celebration to honor Dr. Ruth Bishop, who discovered rotavirus in 1973, and featured remarks and presentations from leading virologists and experts in the rotavirus field, including Dr. Steele.

In other news, PATH hosted its 3^rd Annual Manufacturers Meeting for its partners developing the bovine-human reassortant rotavirus vaccine (BRV) candidate. The meeting, which was held in Bangkok, Thailand, on June 17 to 18, brought together all of the manufacturers actively developing the BRV, as well as several supporting organizations. This two-day meeting provided an opportunity to discuss technical aspects of the development of the BRV candidate, including quality-control assays, formulation and process development, clinical evaluation, validation of assays, design of efficacy studies, and regulatory issues.

Stalled progress on a leading childhood killer spurs report and Call to Action

In May, PATH released a new report highlighting the deadly effects diarrheal diseases have on children in the developing world and the lifesaving solutions to prevent and treat this childhood killer. The report, Diarrheal Disease: Solutions to Defeat a Global Killer, emphasizes the need to refocus attention on diarrheal disease and the array of prevention and treatment solutions that exist, including safe water, improved sanitation and hygiene, vaccines, zinc treatment, and oral rehydration therapy/oral rehydration solution. The report’s accompanying Call to Action unites advocates from the health, development, environmental, water/sanitation, and research communities to raise the visibility of diarrhea and solutions to address it. These more than 90 organizations, such as the United Nations Foundation, Save the Children, and WaterAid America, have joined together to reach donors, international health policymakers, national leaders, and the private sector to push for increased funding and political will to reduce death and illness from diarrheal disease. With a coordinated effort, children do not have to continue dying from this preventable illness.

Journal article highlights the need for vaccination against deadly diarrheal disease in Africa

An article published in the May issue of the journal Science underscores the need for reevaluating the use of cholera vaccines in Africa. Drs. Richard Walker, A. Louis Bourgeois, and Duncan Steele of PATH contributed to the policy forum article (subscription required), which describes the cholera crisis in Africa and the need for flexibility in prevention and treatment efforts. The article proposes a new strategy for curbing the deadly cholera outbreaks that have been raging across Africa for more than a decade. By combining the current use of oral rehydration solution with a mass vaccination effort using cholera vaccines, the number of deaths from this preventable disease could be dramatically reduced.

Vaccine Resource Library highlights

New items featured on PATH’s Vaccine Resource Library include:

• A brand-new section on malaria resources, which includes Clinical Trials: Steps in Malaria Vaccine Development, a PATH fact sheet on malaria vaccine trials, and The Global Malaria Action Plan for a Malaria-Free World, a framework for action from the Roll Back Malaria Partnership. (PATH’s work on malaria vaccine development is managed by the Malaria Vaccine Initiative, a PATH program.)
• Post-Marketing Surveillance of Rotavirus Vaccine Safety, a recent World Health Organization manual on monitoring the safety of rotavirus vaccines.
• Emergence of a Novel Swine-Origin Influenza A (H1N1) Virus in Humans, a new journal article on the influenza A (H1N1) outbreak in the United States.

Upcoming conferences and events

• Vaccines for Enteric Diseases, Malaga, Spain, September 9 to 11. This conference brings together experts in the fields of vaccines and enteric diseases and will address a variety of issues around research, development, and evaluation of vaccines for enteric infections. Participants will attend sessions on disease burden, the state-of-the-field, and clinical trials, among other topics. In addition to co-sponsoring the event, PATH’s Dr. Duncan Steele is serving as chair of the conference and several PATH staff will present and moderate sessions at the meeting.
• Developing Country Vaccine Manufacturers Network Annual Meeting, Beijing, China, September 14 to 18. This conference brings together vaccine manufacturers from developing countries to exchange ideas and discuss topics related to vaccine needs in low-resource countries. This year’s conference, hosted by China National Biotec Group, will provide participants with a forum for discussing topics related to disease burden, vaccine research and development, regulatory approval, and more. Dr. John Boslego, director of PATH’s vaccine development program, will present on PATH’s work to accelerate the development of new vaccines for populations in low-resource countries.
• 3^rd Vaccine Global Congress, Singapore, October 4 to 6. This annual conference, hosted by the journal Vaccine, gives participants access to a state-of-the-art report on the development of vaccines for infectious and non-infectious diseases. Participants will hear from experts and opinion leaders in the field and network with academics and researchers, regulatory and governmental agencies, charities, and health and industry professionals.
• 44^th US-Japan Conference on Cholera and Other Bacterial Enteric Infections, San Diego, CA, October 12 to 14. Part of the US-Japan Cooperative Medical Science Program, a joint cooperative research effort in the medical sciences that concentrates on health problems in Southeast Asia, this conference brings together leading Japanese, American, and other experts in enteric diseases. Participants will discuss the latest scientific advances in vaccines, epidemiology, and research related to cholera and other bacterial enteric infections.
• 5^th African Rotavirus Symposium, Accra, Ghana, October 14 to 17. This symposium brings together diarrheal disease experts to discuss rotavirus in Africa. The symposium, held in conjunction with the 30^th African Health Sciences Congress, will include topics related to rotavirus disease burden and surveillance, vaccine research and development, and clinical trials.

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 Project. 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.

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