PATH receives funding to assess new rotavirus vaccine candidates

PATH’s vaccine development program recently broadened its scope with a new grant from the Bill & Melinda Gates Foundation for US$989,356 over two years to assess non-replicating rotavirus vaccine (NRRV) candidates. Several organizations have been developing NRRVs, but none have been evaluated in humans yet. Last year, PATH conducted a landscape analysis of NRRV approaches currently in development and convened an expert discussion to review the results. Based on this research, two candidates (virus-like particles and inactivated rotavirus) were initially identified for possible advancement to proof-of-concept clinical studies. Recently, additional candidates have also been identified. This project will serve as a planning step to confirm that process development, manufacture under current Good Manufacturing Practices, and early clinical development are warranted and feasible for selected NRRV candidates. If so, PATH will also begin preparatory activities for the advancement of one or more candidates into preclinical and clinical development.

Encouraging trial results for a vaccine candidate against a leading cause of diarrhea

The initial findings from a Phase 2b challenge study of an oral enterotoxigenic Escherichia coli (ETEC) vaccine candidate, ACE527, indicate that it had an overall positive impact on the reduction of disease incidence and severity as well as shedding of the challenge organism. However, the primary endpoint for the study, to significantly reduce the incidence of moderate to severe diarrhea, was not met. This live, attenuated whole cell vaccine candidate, developed by the Danish biotechnology company TD Vaccines, is comprised of three ETEC strains and was tested in 56 adult volunteers at Johns Hopkins University’s Center for Immunization Research in Baltimore, Maryland. PATH’s enteric vaccine project funded the trial, and the complete data analysis is expected to be available in February 2011.

Mekong regional health leaders convene to discuss diarrhea control

In partnership with the Vietnam Ministry of Health and the National Pediatric Hospital of Vietnam, PATH hosted a regional workshop to highlight solutions available for defeating diarrheal disease. Policymakers and health officials shared evidence and lessons learned from projects that are bringing proven interventions to vulnerable communities, including PATH’s work in Vietnam to implement an integrated approach to diarrheal disease control. The workshop was funded in part by PATH’s enteric vaccine project and featured robust discussions on the role of vaccines within diarrhea control programming, including vaccines against cholera and rotavirus.

New partnership to advance research on pneumococcal protein vaccines

PATH’s pneumococcal vaccine project recently entered into a preclinical research agreement with University College London to prioritize antigens for inclusion in pneumococcal protein vaccines. Under the agreement, the partners will evaluate the antibody response to pneumococcal proteins in human sera from diverse geographical regions. Data generated through the characterization of immunodominant antibody responses as part of this project could help advance the pneumococcal vaccine field and provide valuable insights into the design of future pneumococcal protein vaccines to meet needs in the developing world.

Vietnamese vaccine manufacturer and PATH collaborate to expand influenza vaccine resources

PATH recently formed a new partnership with the Institute of Vaccines and Medical Biologicals (IVAC) of Vietnam to help enhance sustainable influenza vaccine production in the country as part of a US$7.9 million project funded in full by the US Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA). IVAC, a state-run developer and producer of vaccines and other biological products, recently completed construction of a new influenza vaccine manufacturing facility with support from the World Health Organization (WHO) and other international partners prior to this project. Under the new collaboration agreement, PATH and IVAC are working together to prepare this facility for the production of influenza vaccines that meet international quality standards. Ultimately, the partners aim to advance an influenza vaccine candidate into clinical evaluation as part of a larger effort to increase local and regional vaccine supplies and to improve real-time response capacity in influenza outbreaks. The collaboration builds upon support that BARDA is providing to the WHO to help vaccine manufacturers in low- and middle-resource countries prepare for eventual licensure and commercial-scale manufacturing of influenza vaccines.

PATH’s vaccine development projects add new members to their scientific advisory boards

Scientific advisory boards, comprised of key experts in their fields, provide strategic guidance to several of PATH’s vaccine development projects. Board members play a key role in shaping project portfolios, meeting regularly to provide input on prioritizing technologies, reviewing data and progress, and providing strategic recommendations. PATH greatly appreciates the support provided by these experts and recently welcomed new members to the scientific advisory boards for its pneumococcal vaccine project, enteric vaccine project, and influenza vaccine project.

Recent scientific publications

A number of staff from PATH’s vaccine development program recently contributed to new scientific publications, including the following articles:

• Development of strategies to overcome barriers to effective mucosal immunization of infants in developing countries (PDF) provides a summary of the discussions at a workshop hosted by the Old Herborn University Foundation in June 2010 to examine the mechanisms that may contribute to the poor response of infants in developing countries to oral vaccines. Drs. Richard Walker, A. Louis Bourgeois, and Lillian Van De Verg authored this article that appeared in the Old Herborn University Seminar Monograph (PDF), which includes several papers focused on specific workshop topics.
• GMP-grade pneumococcal whole-cell vaccine injected subcutaneously protects mice from nasopharyngeal colonization and fatal aspiration-sepsis details research conducted at Children’s Hospital Boston with support from PATH to determine the performance of subcutaneous injection of pneumococcal whole-cell vaccine in preclinical studies. Dr. Mark Alderson, Andi Tate, Dr. Jean-Francois Maisonneuve, and Dr. George Robertson co-authored this article, which appeared in Vaccine.
• Options for inactivation, adjuvant, and route of topical administration of a killed, unencapsulated pneumococcal whole-cell vaccine describes research conducted at Children’s Hospital Boston with support from PATH showing that killing cells of a noncapsulated strain of Streptococcus pneumoniae with chloroform, tricholorethylene, or beta-propiolactone contributed to the protectiveness of a pneumococcal whole-cell vaccine candidate in preclinical studies. Dr. Mark Alderson, Andi Tate, Dr. Jean-Francois Maisonneuve, and Dr. George Robertson co-authored this article, published in Clinical and Vaccine Immunology.
• Outpatient upper respiratory tract viral infections in children with malaria symptoms in Western Kenya describes a cross-sectional study conducted in Kenya’s Nyanza Province to investigate the burden of viral respiratory disease, including influenza, in malaria-endemic populations, specifically in children five through ten years of age. Dr. Kathleen Neuzil was among the co-authors for this article, which appeared in the American Journal of Tropical Medicine and Hygiene.
• PATH pneumococcal vaccine project provides an overview of this project’s work partnering with public- and private-sector collaborators to accelerate the development of pneumococcal vaccines that can be effective, affordable, and accessible for children in low-resource countries. Dr. Mark Alderson, Dr. Jean-Francois Maisonneuve, Lauren Newhouse, and Dr. John Boslego authored this article, which appeared in Pediatric Health.