I’m pleased to share the newest edition of Vaccines for the Future. As you can see, our newsletter has a fresh new look and more streamlined content, which we hope you will enjoy. In addition to the updates from PATH’s Vaccine Development Program (VAC) highlighted below, I wanted to extend a warm welcome to Dr. John Donnelly, who recently joined us as director of our new polio vaccine project. John has many years of vaccine development experience from his work as an independent consultant and in positions at Novartis and Merck, and we are excited to have him join our team.

I would also like to note that we are currently celebrating this year’s World Immunization Week (April 21 to 28), an initiative led by the World Health Organization (WHO) to unite countries across the globe for a week of vaccination campaigns, public education, and information sharing. This event provides a great opportunity to spotlight the importance of immunization in saving lives worldwide.

Sincerely,

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

PATH’s enteric vaccine project and Johns Hopkins University recently completed an evaluation of two lower doses (10⁵ and 10⁶ CFU) of an enterotoxigenic Escherichia coli (ETEC) strain for use in a challenge model for assessing the protective efficacy of vaccine candidates in humans. Diarrhea and other symptoms were split evenly between the two dose groups, and the attack rates were well below 50 percent. Therefore, it is unlikely that these lower doses can be used in future challenge studies because the attack rate would be too low, and the sample size requirements would not be practical. This research built on a 2009 study which determined that the standard ETEC challenge model dose could be reduced 100-fold (to 10⁷ CFU) and still determine effectiveness with a 70 percent attack rate.

In other news, an ascending-dose Phase 1 study of the double-mutant heat-labile toxin (dmLT) adjuvant conducted by the US National Institutes of Health’s Division of Microbiology and Infectious Diseases has completed dosing its final cohort, with no significant product-related adverse events reported to date. These safety results are critical for PATH’s work, as the dmLT will be tested in conjunction with several oral enteric vaccine candidates beginning this year.

PATH’s non-replicating rotavirus vaccine (NRRV) project partnered with the Walter Reed Army Institute of Research (WRAIR) to produce master and working cell banks of the P2-VP8 vaccine candidate from the US National Institutes of Health (NIH). WRAIR also produced a clinical vaccine lot under Good Manufacturing Practice (GMP) conditions. WRAIR is currently filling bulk vaccine into final vials and aims to release the lot by May 2012, ultimately to evaluate the P2-VP8 (NIH) candidate in Phase 1 trials among healthy US adults later this year. The NRRV project has also contracted Advanced Bioscience Laboratories (ABL) to conduct a preclinical study on this vaccine lot to determine toxicity, local site reactogenicity, and immunogenic potential. ABL is initiating the toxicity study at Avanza Laboratories this month.

In February, PATH organized a workshop on vaccine quality and risk assessment for six Chinese vaccine manufacturing institutes — Changchun, Chengdu, Lanzhou, Shanghai, Wuhan, and Beijing Tiantan Bio, all affiliated with the China National Biotec Group (CNBG). Participants appreciated the chance to consider how best to apply GMP in everyday processes and procedures.

The five-day training, conducted by PATH staff and consultants, was the first step in PATH’s one-year project to support CNBG by assessing the readiness of their manufacturing facilities to meet new Chinese manufacturing standards and WHO prequalification requirements. The project continues with site visits to conduct assessments at the individual institutes.

PATH staff joined researchers and clinicians from around the world at the eighth International Symposium on Pneumococci and Pneumococcal Diseases from March 11 to 15, 2012 in Iguaçu Falls, Brazil. As a conference co-sponsor, PATH helped bring into focus efforts to develop new, affordable pneumococcal vaccines for children in the developing world. Dr. Mark Alderson, director of PATH’s pneumococcal vaccine project, co-chaired a session on novel pneumococcal vaccines and their regulatory pathways, during which partners such as Children’s Hospital Boston and GlaxoSmithKline Biologicals SA showcased collaborations with PATH to advance new vaccines in the clinic. Other PATH partners highlighted preclinical vaccine research and development work through poster presentations, including Genocea Biosciences and Serum Institute of India, Ltd. PATH also hosted a booth in the exhibition hall, providing a central location for participants to learn about PATH’s work and the importance of tailoring new pneumococcal vaccines to needs in low-resource countries.

March 2012:

• A Phase 1 trial of a Shigella inactivated whole cell vaccine enrolled an additional cohort of 25 healthy adults in Baltimore, Maryland. Given the modest immune response demonstrated in the previous cohort of this dose-escalation trial, the new cohort will test a higher dose level (10¹¹ vaccine particles) to see if it enhances the level of the immune response and increases the proportion of responders.
• A Phase 1 trial of an inactivated tetravalent ETEC vaccine administered alone and in combination with the dmLT adjuvant was launched in Gothenburg, Sweden, and will enroll 120 healthy adults.
• A Phase 1 trial of an inactivated Streptococcus pneumoniae whole cell vaccine administered in combination with aluminum hydroxide adjuvant launched in Tacoma, Washington, and will enroll 42 healthy adults.

April 2012:

• A Phase 1 trial of a live attenuated avian influenza A/H7N3 vaccine launched in St. Petersburg, Russia, and will enroll 40 healthy adults.

A number of activities being advanced by PATH’s Technology Solutions (TS) Global Program are aimed at facilitating the use of inactivated polio vaccine (IPV) as a wide-scale alternative to oral polio vaccine. Vaccine delivery technology experts in TS are working in partnership with WHO and the Global Polio Eradication Initiative to explore the potential of alternative delivery devices and methods, such as needle-free disposable-syringe jet injection and intradermal delivery, to facilitate reductions in the required dose and therefore cost per dose of IPV. These efforts build on work undertaken in 2010, when PATH published an analysis of various delivery strategies for reducing the cost of IPV. Such project activities also complement the work of TS formulation scientists working in the space of vaccine adjuvants and VAC’s recently launched work in IPV product development and clinical research, which are helping to elucidate the promise of IPV as an appropriate and affordable tool in the fight to eradicate polio and sustain immunization in the post-eradication era.