Promise and Challenges of Biotech Vaccines

Several recent approvals highlight progress in developing both prophylactic and therapeutic vaccines. A session at the AAPS National Biotechnology Conference, entitled "New Vaccines Technologies" explored these promising results as well as ongoing challenges.

The Good News

Lee Roberts, PhD, formerly of PowderJect Vaccines Inc. (Madison, WI), presented an overview of the DNA vaccine field. Despite 20 years of DNA vaccine research and development, with promising preclinical results, clinical results have been disappointing. However, a recent review of published clinical studies indicates that DNA vaccines are capable of inducing an immune response, particularly cell mediated immunity (CMI), when vaccination strategies other than simple intramuscular injection of DNA plasmid are pursued. For example, recent study findings showed both antibody and CMI responses to the hepatitis B virus (HBV), delivered using the proprietary PowderJect particle-mediated epidermal DNA vaccine delivery system (PowderMed, LTD, Oxford, UK, www.powdermed.com). Using this system, the DNA vaccine is first coated onto microscopic gold particles, which are then propelled into the antigen-presenting cells of the skin.  Initial testing has rendered a ≥ 10-fold boost in the subject’s serum antibody titers and significant CMI responses specific for the HBV antigen. Given these changes in vaccination strategy, researchers now recognize that DNA-based vaccines may be most favorable for therapeutic applications, through induction of a CMI response, versus the typical antibody response derived from traditional vaccines.

Significant headway also has been made developing viable therapeutic vaccines to fight cancer. Michael G. Hanna, Jr., PhD, chief scientific officer of Intracel Resources (Frederick, MD, www.intracel.com), described his company’s long journey to develop Oncovax, a vaccine to be used in tandem with surgery for stage 2 colon cancer patients. Oncovax is an autologous vaccine therapy in which cells are extracted from a patient’s own tumor after surgery. The cells are irradiated and injected back into the patient to stimulate an immune response against the tumor, thus-it is hoped-preventing recurrence. In five clinical studies conducted to date in 700 patients, the vaccine has significantly reduced the recurrence of the disease, leading to an approximately 60% improvement in the recurrence-free interval for patients with the disease. Significant improvements were also seen in overall survival rates.

Another recent advance for vaccines is the development of a method to store vaccines without refrigeration. Kevin Killeen, PhD, senior director of bacterial vaccines at Avant Immunotherapeutics (Needham, MA, www.avantimmune.com), explained that the company’s “VitriLife” process allows vaccine product, in vials or bulk, to be stored at 25° C or higher. The process is conducted in a lyophilizer, but no freezing is involved. “We boil the sample in the presence of sugar,” said Killeen, “and then mill it into a powder.” Killeen believes that this process will lowerthe cost of goods and facilitate the development of combination vaccines.

Ongoing Challenges

Despite advances however, many challenges remain in developing new vaccines. Ten years ago, there were 79 vaccines in Phase 2 development; in 2006, only 11 of the original 79 potential therapeutics are currently licensed in the US, said Peter A. Patriarca, MD, of Biologics Consulting Group (Bethesda, MD, www.bcg-usa.com). Biologic vaccine therapy poses unique obstacles for developers.  Because most biologic vaccines are totally new products, there is no history or experience to rely on when anticipating how subjects will respond to the drug. Also, promising preclinical results in animal models often are not duplicated when the therapy is tested in humans. Additionally, cell-based therapies pose manufacturing challenges, because most of them are unique products. Often, it is challenging to develop robust manufacturing processes and to validate quality control assays for these products; a specific biological assay may have to be developed for each individual product.

Wyeth Pharmaceuticals’ (Collegeville, PA, www.wyeth.com) director of global technology transfer for vaccines, Ranjit R. Deshmukh, PhD, discussed scale-up and manufacturing issues for biologic vaccine production. Because clinical trials for vaccines are very large, a lot of material is needed, and scale-up of cell-based methods may not be linear. Facility readiness is also a concern, because it takes longer to set up a new vaccine facility than a facility for other biotech products. Also fill/finish guidelines and procedures for vaccines warrant particularly strict regulatory requirements; unlike drugs, vaccines are usually administered to healthy individuals, often infants. Some vaccine products, such as those in a suspension that contains an adjuvant or multi-strain vaccines that contain multiple components, require great care in filling. Deshmukh cited the example of the Prevnar vaccine, which requires a total of 14 or 15 separate processes, to make seven different polysaccharides and a carrier protein, and then seven conjugates. “These long lead times affect decisions during development,” he said. “In cases like these, you have to make manufacturing decisions earlier in development so that youcan be ready for trials and commercial manufacturing.”

-Pam Holland-Moritz