In this issue:
This new issue of Vaccines for the Future
includes a number of updates from our growing vaccine development program at PATH. We highlight new clinical trials related to influenza vaccines and kick-off activities related to our newest project addressing respiratory syncytial virus vaccines. We also report on two recent gatherings in the vaccine field that highlighted work going on in our pneumococcal and enteric vaccine projects, as well as new training sessions for partners of our rotavirus vaccine development project. In addition, we share our plans for World Pneumonia Day and highlight the work of our colleagues in PATH’s Malaria Vaccine Initiative. Finally, we include our usual updates on recent scientific publications from our staff, upcoming conferences and events, and current job opportunities.
We also share the excitement over the GAVI Alliance’s recent announcement that it will provide funding for 16 more countries to introduce rotavirus vaccines, 18 more countries to introduce pneumococcal vaccines, and 17 additional countries to introduce other vaccines. Out of these 37 countries, 24 are in Africa. This marks a huge step toward saving the lives of millions more kids in low-resource countries by reaching them with critical vaccines, particularly those that prevent pneumonia and diarrhea, which we know are the biggest killers of children under age five. We congratulate GAVI on this major milestone, and look forward to the day when the vaccines we have in development are among those GAVI makes available to countries most in need.
As always, we hope you enjoy this issue of our newsletter, and we welcome any feedback you may have.
John W. Boslego, MD
Director,Vaccine Development Global Program
PATH-supported vaccine trials seek more efficient ways to control influenza
PATH’s influenza vaccine project, the Johns Hopkins Bloomberg School of Public Health, and the US National Institute of Allergy and Infectious Diseases launched an open-label clinical study in October to evaluate the degree to which previous receipt of an avian A/H5N1 live attenuated influenza vaccine (LAIV) enhances immune responses to a 45 µg dose of inactivated, unadjuvanted influenza A/H5N1 vaccine in healthy adults. While the LAIV is only moderately immunogenic by conventional antibody measurements, the partners hypothesize that it may help broaden and/or heighten protection against subsequent infection or vaccination. This could be an important proof-of-concept study that contributes to the understanding of how LAIVs work.
In related news, PATH recently received a new cooperative agreement from the US Centers for Disease Control and Prevention (CDC), which the CDC is funding in full for US$3.75 million over three years. The new agreement extends PATH’s work in Senegal (PDF) to evaluate the effectiveness of influenza vaccines in tropical Africa and to gain a better understanding of influenza disease patterns in this setting.
Respiratory syncytial virus vaccine project launches advisory board and web text
The start-up phase of PATH’s new respiratory syncytial virus (RSV) vaccine project is underway, kicking off with the establishment of a scientific advisory board comprised of key vaccine experts to provide strategic guidance for the RSV vaccine project. The board, which convened for the first time on September 16, plays a key role in shaping the RSV project portfolio. Going forward, the members will meet periodically to provide input on prioritizing technologies, review data and progress, and provide strategic recommendations. In addition, the RSV project launched new text
on PATH’s website to highlight the work being conducted and provide background information on the disease.
Symposium convenes to advance pneumococcal vaccine development in China
PATH sponsored a symposium from October 20 to 21 in Beijing, China, that brought together international experts and scientific staff from potential Chinese pneumococcal conjugate vaccine (PCV) manufacturers to discuss key issues surrounding the development of PCVs in China and other emerging markets. The nearly 50 participants shared knowledge and experience to help advance PCV development in China, clarify a path toward World Health Organization prequalification for Chinese PCVs, and ensure the suitability of these PCVs for markets in the developing world where need is greatest. From PATH’s pneumococcal vaccine project
team, Drs. Mark Alderson and Dr. Sheau-Mei Cheng delivered opening remarks, and Dr. Jeff Maisonneuve chaired a round-table discussion on regulatory issues and international marketing for PCVs. Overall, the information exchanged at the symposium helped advance larger efforts by PATH and other global health organizations to foster competitive markets that include emerging-country manufacturers like those in China—a critical strategy for making lifesaving vaccines such as PCVs sustainably affordable, available, and accessible for low-resource countries.
Help spread the word about World Pneumonia Day on November 12
Join PATH in commemorating World Pneumonia Day on November 12 and raise awareness about the urgent need to prevent infants and young children around the world from dying of pneumonia. Pneumonia is the world’s leading killer of children under five years of age due to infectious disease, causing one in every five child deaths, mainly in the developing world. In honor of World Pneumonia Day, PATH is spreading the word via Facebook, Twitter, and other outlets about the importance of prioritizing pneumonia and making prevention and treatment options affordable and accessible for vulnerable populations. For more information about how to help in the fight against pneumonia, visit the World Pneumonia Day website. Also, check out PATH’s website for updates on its activities for World Pneumonia Day and on its work to advance the development of new, low-cost vaccines against pneumonia’s leading cause, Streptococcus pneumoniae.
Major conference on vaccines against diarrheal diseases features PATH’s work
Several PATH staff members joined top researchers from around the world at the 6th International Conference on Vaccines for Enteric Diseases from September 14 to 16 in Cannes, France, to discuss advances in the field. PATH was a co-sponsor of the conference, which included eight presentations featuring the work of its enteric vaccine project to develop new, affordable vaccines against enterotoxigenic Escherichia coli and Shigella
for young children in resource-poor countries. Three additional speakers also cited PATH’s role in supporting parts of their studies. Numerous partners were represented at the conference, including the Johns Hopkins Bloomberg School of Public Health, Mucosis B.V., Oklahoma State University, TD Vaccines, Tufts University, Tulane University, University of Gothenburg, University of Maryland in Baltimore, the US Naval Medical Research Center, and the Walter Reed Army Institute of Research.
In addition, Dr. Duncan Steele, a senior technical advisor for PATH’s Vaccine Development Global Program at the time of the event, served as the scientific chair and delivered a keynote address at the opening of the conference. Dr. Steele reminded the enteric vaccine experts in attendance to consider the broad impact of diarrheal disease and the role of vaccines within an integrated approach that includes a comprehensive array of interventions, including hygiene and sanitation, safe water, oral rehydration therapy, zinc treatment, and breastfeeding.
PATH conducts additional formulation training for rotavirus vaccine manufacturers
In follow-up to an April 2011 article in Vaccines for the Future, PATH has now completed two additional training sessions on the rotavirus vaccine formulation that Aridis Pharmaceuticals and PATH co-developed; one with Brazil’s Instituto Butantan on July 5 to 12 and another with China National Biotec Group’s Wuhan Institute of Biological Products on August 29 to September 2. PATH’s rotavirus vaccine development project
supports several emerging-country manufacturers actively developing the bovine-human reassortant vaccine (BRV) through a “shared technology platform,” which includes access to an optimized liquid formulation that they may choose to evaluate further with their BRV candidates. As with the first training, staff from PATH’s Technology Solutions Global Program conducted the sessions at its headquarters in Seattle, Washington. The trainings included a review of the blending procedure, the successful preparation of several batches of formulation (without BRV) along with scale-up, preparation of reagents, stability testing, and formulation troubleshooting. PATH will continue to provide technical support to these manufacturers on using the liquid formulation and may conduct further training sessions for other partners if requested.
Recent scientific publications
2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: A systematic review and meta-analysis reports on a study conducted by PATH, the World Health Organization, and the US Centers for Disease Control and Prevention, to estimate the number of deaths in children less than five years of age due to rotavirus diarrhea globally and nationally. Dr. Duncan Steele was a co-author of this article published in The Lancet Infectious Diseases.
A combination vaccine consisting of three live attenuated enterotoxigenic Escherichia coli strains expressing a range of colonization factors and LTB is well tolerated and immunogenic in a placebo-controlled double-blind Phase 1 trial in healthy adults describes the results of a Phase 1 trial of a trivalent, live attenuated ETEC vaccine candidate, ACE527, produced by TD Vaccines. The study, conducted by the Johns Hopkins Bloomberg School of Public Health and supported by PATH, indicated that ACE527 had a strong safety profile and promising initial immunological data, warranting further clinical testing. Drs. Lou Bourgeois and Richard Walker were co-authors of this article published in Clinical and Vaccine Immunology.
Establishment of a new human pneumococcal standard reference serum 007sp reports on a study that resulted in the development of a new pneumococcal reference serum to replace the dwindling stocks of Lot 89SF, the reference standard serum pool used since 1990. The new serum is essential for ongoing efforts to evaluate new vaccines while maintaining the link to the original serology performed as part of the pivotal efficacy studies conducted prior to licensure. Dr. Jeff Maisonneuve was a co-author of this article published in Clinical and Vaccine Immunology.
Formulation of a killed whole cell pneumococcus vaccine—effect of aluminum adjuvants on the antibody and IL-17 response describes preclinical research, conducted by Purdue University and supported by PATH, which demonstrates that a vaccine composed of killed whole cell, nonencapsulated pneumococci and formulated with aluminum hydroxide induces a strong antibody and IL-17 response. Dr. Jeff Maisonneuve was a co-author of this article published in the Journal of Immune Based Therapies and Vaccines.
Refinement of a human challenge model for evaluation of enterotoxigenic E. coli (ETEC) vaccines reports on a study conducted by the Johns Hopkins Bloomberg School of Public Health and sponsored by PATH, which found that a lower dose than used previously of the human challenge model for ETEC diarrhea using strain H10407 is sufficient for determining the effectiveness of a vaccine candidate. Drs. Lou Bourgeois and Richard Walker were co-authors of this article published in Clinical and Vaccine Immunology.
Also@PATH: Accelerating malaria vaccine development
In addition to the diseases addressed under PATH’s Vaccine Development Global Program, the PATH Malaria Vaccine Initiative (MVI) is working to accelerate the development of malaria vaccines and to ensure their availability and accessibility in the developing world. Every year there are about 225 million cases of malaria, a parasitic infection transmitted by mosquitoes, and nearly 800,000 deaths, mostly among children in Africa under the age of five. These deaths are due largely to the predominance of Plasmodium falciparum, the malaria parasite deadliest to humans, in the Africa region. While consistent use of effective insecticides, insecticide-treated nets, and malaria drugs saves lives, a malaria vaccine is critical to preventing these deaths.
Established in 1999, MVI was founded on the premise that although promising malaria vaccine approaches existed, they required assistance to get out of the laboratory and into clinical trials. MVI establishes strategic partnerships to identify promising vaccine approaches and systematically move them through the development process. Partners include academic institutions, government agencies, biotechs, and pharmaceutical companies, with MVI providing technical, scientific, financial, and project management expertise as needed. MVI maintains a diverse portfolio
of preclinical and clinical products, and currently has one vaccine candidate and two approaches under clinical development. The most advanced is GlaxoSmithKline Biologicals’ RTS,S, which targets the pre-erythrocytic stages of P. falciparum and is now in a large-scale Phase 3 efficacy trial at 11 sites in 7 African countries. Initial results from this trial show that RTS,S reduces the risk of malaria by half in children aged 5 to 17 months. In addition to vaccine approaches that are similar to RTS,S, MVI is also supporting those that seek to block malaria transmission and is increasing its focus on P. vivax, the parasite that causes a less deadly—but more widespread—form of malaria.
Upcoming conferences and events
- 12th Annual General Meeting of the Developing Country Vaccine Manufacturers Network, Xiamen, China, October 30 to November 2. This meeting brings together vaccine manufacturers based in developing countries to share ideas and experiences, and will include special sessions focused on building up capabilities and expertise in exchanging technology-based information. Dr. Sheau-Mei Cheng, senior program officer for PATH’s pneumococcal vaccine project, will attend this meeting.
- Vaccine Development and Approval: Phase 2 and Beyond, Philadelphia, Pennsylvania, November 7 to 8. This conference is for industry and regulatory professionals to discuss the use of adaptive designs for vaccine trials and the inherent challenges of vaccine trials, as well as featuring examples of novel approaches to licensure and the lessons learned in the pathway to approval. Dr. Jeff Maisonneuve, scientific director for PATH’s pneumococcal vaccine project, will present on “Paths to vaccine approval.”
- Malnutrition, Gut-Microbial Interactions, and Mucosal Immunity to Vaccines, New Delhi, India, November 7 to 11. This meeting, which is part of the Keystone Symposia Global Health Series, will focus on understanding the role of nutrition in modulating gut immunity to vaccines in order to formulate strategies for improving the performance of enteric vaccines in malnourished children. Dr. Richard Walker, director of PATH’s enteric vaccine project, will present on “Developing ETEC and Shigella
vaccines for children in developing countries” and chair a session entitled, “Strategies for improving the immunogenicity of enteric vaccines.”
- Vaccines Europe 2011, Brussels, Belgium, November 30 to December 1. This event brings together leading experts in the vaccine field to present and discuss the latest vaccine research, improved production methods, analytical advances, and regulatory updates. Dr. Jeff Maisonneuve, scientific director for PATH’s pneumococcal vaccine project, will be a keynote speaker presenting PATH’s latest work in pneumococcal vaccine development.
- Fourth International Rushmore Conference on Enteric Diseases, Chicago, Illinois, December 3 to 4. This conference will provide a dialogue between biomedical and veterinary medical researchers whose focus is enteric diseases of humans and animals that have similar etiologies. Dr. Richard Walker, director of PATH’s enteric vaccine project will present on “Strategies in the development of enteric vaccines against Shigella and ETEC.”
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 vaccines for the global population against influenza, meningitis, and respiratory syncytial virus. 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, the Research Council of Norway, the US Department of Health and Human Services, and the United Kingdom’s Department for International Development. Some projects within the vaccine development program are funded by PATH Vaccine Solutions.
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