Welcome to the new issue of Vaccines for the Future, featuring updates from across PATH’s Vaccine Development Program (VAC). In addition to the news below, we are pleased to announce follow-on funding from the Bill & Melinda Gates Foundation for our pneumococcal vaccine project. The new grant is for up to US$59.6 million through the end of 2017 and will allow us to further develop our lead pneumococcal protein vaccine candidates, including the killed whole cell vaccine.
Our pneumococcal vaccine project, which began in February 2006, was the vanguard effort of what has become VAC. Since the outset, we have explored 11 vaccine candidates and approaches, and conducted broader research to advance the field more generally, including establishing a library of developing world pneumococcal strains, refining preclinical disease models, and sequencing the genomes of five geographically diverse Streptococcus pneumoniae isolates. The work of the past six years has led to our current priorities: accelerating development of a low-cost conjugate vaccine, pursuing clinical development of an inactivated whole cell vaccine candidate against pneumococcal bacteria, and continuing to explore additional approaches to pneumococcal protein vaccines and polysaccharide / common protein conjugate vaccines using novel technologies.
John W. Boslego, MD
Director, Vaccine Development Program
Rotavirus vaccine reaches late-stage clinical development
PATH’s rotavirus vaccine development project is working in partnership with Serum Institute of India, Ltd. (SIIL) to evaluate the safety and efficacy of their bovine-human reassortant rotavirus vaccine (BRV) in a large-scale, multi-center Phase 3 trial in India. The trial will be a randomized, double-blind, placebo-controlled study enrolling infants in several locations throughout India. This work is being supported by a grant from the Bill & Melinda Gates Foundation for approximately $30 million over five years. Rotavirus is the leading cause of severe childhood diarrhea, and accounts for 37 percent of all child deaths from diarrhea worldwide.
PATH and SIIL have already completed a range of activities to prepare for the Phase 3 trial, including identifying potential trial sites, conducting preparatory studies at several of the sites, and finalizing the manufacturing process and formulation of the vaccine. The BRV is an oral, live attenuated pentavalent, lyophilized vaccine administered orally to infants in a three-dose course at the ages of approximately 6, 10, and 14 weeks. Enrollment will begin by mid-2013 and the trial will last about three years.
New partnership for non-replicating rotavirus vaccine research
PATH’s non-replicating rotavirus vaccine project acquired a non-exclusive sublicense from LigoCyte Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, to manufacture, distribute, and sell the P particle-VP8 rotavirus vaccine candidate in China. The vaccine candidate is currently in preclinical development. This sublicense expands upon a license previously obtained from the Cincinnati Children’s Hospital and Medical Center for the candidate’s manufacture, distribution, and sale in developing countries.
Promising results for a new pneumococcal vaccine
PATH’s pneumococcal vaccine project recently received results of the Phase 1 dose-escalation trial of an inactivated Streptococcus pneumoniae whole cell vaccine (SPWCV) under development in partnership with Boston Children’s Hospital. The SPWCV was formulated with aluminum hydroxide and administered three times at three dose levels in healthy adults. Preliminary results demonstrate an acceptable safety and reactogenicity profile for SPWCV along with positive immunogenicity results that support continuing clinical development. Full analysis of the results will be published in the near future and the next study is planned for healthy Kenyan adults and toddlers.
In other news, PATH co-hosted a meeting in November 2012 with the World Health Organization (WHO) to understand the clinical and regulatory challenges in the development of protein vaccines for Streptococcus pneumoniae and to map out a possible pathway for their licensure and WHO prequalification. Specific focus was given to the role of nasopharyngeal carriage studies in proof-of-concept and licensure trials, possible designs for Phase 2 and 3 clinical trials, and regulatory strategies and pathways to licensure.
Assisting Chinese and Brazilian vaccine manufacturers
In December 2012, PATH completed the initial work to support the China National Biotec Group (CNBG) by assessing the readiness of their manufacturing facilities to meet new Chinese manufacturing standards and WHO prequalification requirements. Over the past year, PATH conducted training on Good Manufacturing Practice, performed site visits at the individual institutes—Changchun, Chengdu, Lanzhou, Shanghai, Wuhan, and Beijing Tiantan Bio—to conduct assessments and identify remediation needs, and finally presented recommendations to CNBG that were well received. PATH also conducted training and completed assessments at three state-owned vaccine manufacturing institutes in Brazil—Bio-Manguinhos, the Butantan Institute, and Ezequiel Dias Foundation. PATH will make follow-up visits and prepare the remediation recommendations for Brazil this quarter.
New partnership to develop a Shigella vaccine
PATH’s enteric vaccine project recently entered into a new joint partnership with the Walter Reed Army Institute of Research (WRAIR) and icddr,b (a Bangladesh-based international public health research institution) to support the clinical development of a Shigella sonnei vaccine candidate to address one of the leading bacterial causes of diarrhea among children in low-resource settings. PATH and icddr,b will evaluate WRAIR’s oral, live attenuated WRSS1 candidate for safety and immunogenicity in a descending-age study in Bangladesh, which is expected to launch in February 2013.
RSV project establishes new research partnership
Under an agreement with the University of Warwick, PATH is working with Dr. James Nokes through the Kenya Medical Research Institute to evaluate the relationship between maternal respiratory syncytial virus (RSV)-specific antibody and protection in infants, as well as the rate at which antibody protection declines from birth using samples collected from newborns in Kilifi, Kenya. These studies will help identify a target RSV neutralizing antibody concentration for protection. Overall, the new partnership 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 related news, PATH is maintaining an RSV vaccine snapshot (170 KB PDF) in order to track the development of RSV vaccine candidates and provide a summary of all the various vaccine approaches being worked on worldwide. PATH will update this landscape snapshot regularly, and welcomes input from those working in the RSV vaccine field.
PATH participates in WHO influenza vaccine meeting
In January 2013, PATH’s Drs. Kathleen Neuzil and Vadim Tsvetnitsky participated in the First WHO Integrated Meeting on Development and Clinical Trials of Influenza Vaccines that Induce Broadly Protective and Long-Lasting Immune Responses which took place in Hong Kong. Dr. Neuzil co-chaired a session on vaccine delivery methods, and several of PATH’s influenza vaccine project
partners gave presentations featuring their collaborations with the project. The goals of the meeting were to review the current status of research in the area of new influenza vaccines and discuss recent data from clinical trials of pandemic and seasonal influenza vaccines. The meeting also focused on defining a research agenda for the accelerated development of novel influenza vaccines.
A Phase 1 trial of the P2-VP8 subunit rotavirus vaccine candidate launched in Baltimore, Maryland. This study of a non-replicating rotavirus vaccine candidate aims to evaluate safety, reactogenicity, tolerability, and immunogenicity of three escalating vaccine dose-levels among 48 healthy adults.
New on PATH’s Vaccine Resource Library
Recent additions to PATH’s Vaccine Resource Library include:
IN THIS ISSUE
VAC IN RECENT SCIENTIFIC ARTICLES
VAC AT UPCOMING EVENTS
World Vaccine Congress & Expo
April 16 to 18
NEW PATH RESOURCES
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.
Learn more about VAC’s work on our program website.
Banner photo: Philippe Blanc