Welcome to the latest issue of Vaccines for the Future, which includes a range of updates from PATH’s Vaccine Development Program (VAC) related to new funding, recent partnerships, clinical trials, and more.

I would like to take this opportunity to congratulate Dr. Kathy Neuzil, former director of VAC’s influenza vaccine project, who recently became the director of PATH’s Vaccine Access and Delivery Program. In this new role, Kathy will oversee PATH’s work on accelerating the introduction of various new vaccines in low-resource settings. As part of this change, some projects that had been housed under VAC will be shifting to Kathy’s program, such as our work on evaluating the currently licensed rotavirus vaccines. In the future, we look forward to continuing to work together, particularly as vaccines in VAC’s portfolio move closer to licensure.

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

The Bill & Melinda Gates Foundation recently awarded PATH nearly US$27 million over five years to support the clinical development and licensure of a low-cost pneumococcal conjugate vaccine (PCV). The PCV will focus on the Streptococcus pneumoniae serotypes that are the most common causes of disease in the developing world at a price that low- and middle-income countries can sustainably afford over the long-term without substantial donor assistance. S. pneumoniae is the leading cause of severe pneumonia and killed approximately 500,000 children under the age of five in 2008 alone, according to the World Health Organization (WHO). This project is one of the mainstays of PATH’s work in pneumococcal vaccines to reduce childhood morbidity and mortality from lower-respiratory infections in low-income regions where pneumococcal disease poses the greatest burden.

PATH recently entered into a new collaborative agreement with the Serum Institute of India, Ltd. (SIIL) to develop and manufacture a thermostable polyvalent meningococcal conjugate vaccine. The collaboration advances the work of PATH’s polyvalent meningitis vaccine project to accelerate the development of an effective, affordable, and accessible vaccine that will prevent disease from meningitis, tailored to needs in the African meningitis belt and other underserved countries. This project builds on the recent success of the Meningitis Vaccine Project, a collaborative effort of PATH and WHO, in partnership with SIIL, to develop and introduce a new meningococcal A vaccine in Africa. However, other cases caused by non-group A meningitis—15 to 20 percent of meningococcal infections—will continue to occur unless an affordable, thermostable, polyvalent meningococcal conjugate vaccine is developed.

No vaccine yet exists for respiratory syncytial virus (RSV), leaving infants and young children vulnerable to a leading cause of acute lower-respiratory infection and inflicting a heavy burden on caregivers and health care systems, particularly in the developing world. Several new partnerships, as part of PATH’s RSV vaccine pilot project, are focused on evaluating feasibility for a maternal immunization strategy to protect children in the earliest months of life from this widespread disease. PATH is providing US$2 million in initial funding to partially support (PDF) Novavax, Inc.’s Phase 2 dose-ranging clinical trial evaluating their RSV fusion (F) protein vaccine candidate’s immunogenicity in women of childbearing age in the United States. In other research, PATH is working with Dr. Ruth Karron at the Bloomberg School of Public Health, Johns Hopkins University, Dr. Christopher King at Case Western Reserve University, and Dr. Willie Pomat and colleagues at the Papua New Guinea Institute of Medical Research to assess the effects of placental malaria on the transfer of RSV-specific neutralizing antibody from mothers to infants.

PATH recently entered into a new collaboration with Mount Sinai School of Medicine to advance preclinical research on broad-coverage influenza vaccines. The project will focus on the development of novel vaccine constructs designed to target conserved neutralizing epitopes of influenza hemagglutinin, which could elicit long-lasting immunity against the broad spectrum of influenza viruses. This work supports PATH’s influenza vaccine project in advancing the development of promising new influenza vaccines that can be accessible and affordable to people in low-resource countries. Vaccines that provide broader protection against diverse strains of influenza, if successful, could be critical for controlling seasonal and pandemic outbreaks, and could help eliminate the need to annually modify vaccines to match the ever-changing influenza viruses in circulation.

PATH participated in two recent high-level gatherings of enteric vaccine experts. As a co-sponsor of the International Workshop on Enteropathogenic Escherichia coli (EPEC) and Shigella, organized by icddr,b (a Bangladesh-based international public health research institution) and held in Argentina in May 2012, PATH helped bring together scientists and researchers from across the globe to discuss disease surveillance, vaccine development, and new techniques for the diagnosis and characterization of EPEC and Shigella. Also in May, Dr. Richard Walker, director of PATH’s enteric vaccine project, participated in a WHO panel of expert consultants to discuss the current state of enteric vaccines and explore how WHO could play a future role in benefitting this field.

PATH’s rotavirus vaccine development project hosted its Sixth Annual Manufacturers Meeting in Bangkok, Thailand from June 13 to 14. This meeting brought together representatives from all of the manufacturers actively developing the bovine-human reassortant rotavirus vaccine (BRV), including: SIIL; Shantha Biotechnics, Inc. from India; and China National Biotec Group’s Wuhan Institute of Biological Products. PATH supports these manufacturers through a unique “shared technology platform” to provide access to technologies, training, methodologies, and materials.

The meeting presentations and discussions covered a range of topics related to rotavirus vaccine development, including the current portfolio of commercial vaccines, clinical aspects, ethical and regulatory perspectives, immunological read-outs, intussusception, controlled-temperature chain, vaccine delivery devices, and public-sector pricing. The manufacturers shared their progress in developing the BRV in their respective countries, and the meeting provided them with a platform for discussing common issues around the development of the BRV as well as enabling them to anticipate their preparation for possible Phase 3 clinical trials and post-licensure Phase 4 studies.

Since February, PATH has completed site visits to six Chinese vaccine manufacturing institutes—Changchun, Chengdu, Lanzhou, Shanghai, Wuhan, and Beijing Tiantan Bio, all affiliated with the China National Biotec Group—to conduct assessments of the readiness of their manufacturing facilities to meet new Chinese manufacturing standards and WHO prequalification requirements. 

PATH has now received supplemental funding from the Bill & Melinda Gates Foundation to expand this effort to conduct similar assessments and make recommendations to address potential gaps in Brazil, at three state-owned vaccine manufacturing institutes—Bio-Manguinhos, the Butantan Institute, and Ezequiel Dias Foundation. The work in Brazil will begin in August and conclude by the end of the year.

April 2012:

• A Phase 1 trial of a monovalent, inactivated whole virus influenza A/H1N1 vaccine launched in Ho Chi Minh City, Vietnam, and will evaluate safety and immunogenicity in 50 healthy adults.

May 2012:

• A clinical-bridging study of the live attenuated SA-14-14-2 Japanese encephalitis vaccine launched in Matlab Upazila, Bangladesh, and will enroll 1,000 healthy children 10 to 12 months of age. The aim is to confirm that the vaccine manufactured at a new facility is as safe and immunogenic as vaccine manufactured at an existing plant.

June 2012:

• A Phase 2 trial of a seasonal, trivalent live attenuated influenza vaccine candidate launched in the Kamalapur Surveillance Site of Bangladesh, and will enroll 300 healthy children 24 through 59 months of age.

Recent additions to PATH’s Vaccine Resource Library include:

• The expansion of the section on human papillomavirus to include more than 60 new resources, such as PATH’s Cervical cancer prevention action planner.
• More than 50 new additional resources since January 2012, including the Draft global vaccine action plan and Policy making for new vaccines in low- and middle-income countries.