For most people, the word "vaccination" brings to mindprevention of disease. Vaccines for smallpox and polio have virtuallyeradicated these diseases with a benefit to society that has been unprecedentedby any other breakthrough in healthcare. Preventive vaccines, dating back tothe era of Jenner and Pasteur, work by boosting the body's resilience toprevent infections.
Over the last century, immunologists have taken a muchbroader view of vaccination. These scientists have explored the possibilitythat vaccines may also be used to treat pre-existing infections and evencancer, in addition to their established role in preventing infectiousdiseases. While the development path for therapeutic cancer vaccines has provenslow, 2012 could be a breakout year for the field with 40 unique agentspresently being tested in over 60 clinical trials. A dozen readouts fromrandomized Phase II or Phase III trials are expected during the next 12 months.
For these and other next-generation therapeutic as well asprophylactic vaccines, the cumulative evidence points to success being largelydependent on activation of T cells and/or a broader range of antibodyresponses. Compounds called adjuvants – agents that boost and prolong theeffect of an antigen-specific vaccine – play an essential and central role inthe ability to achieve these responses. In fact, a number of antigen-specificvaccines have proven ineffective when the right adjuvant is removed from anotherwise potent vaccine formulation.
The use of the adjuvants or adjuvant systems has created newopportunities for therapeutic vaccines. Such vaccines can now be powered toplay a central role in the treatment of cancer, viral illnesses and many otherdiseases, including autoimmune disorders. Given that vaccines work in a muchmore targeted manner than most drugs and use a natural pathway of the body,upon success we are likely to see efficacy and safety profiles not achievedwith most current medicines.
During the last 80 years, many adjuvants have been used inexperimental settings, but only three have made it into routine clinicalpractice: alum, MF59 and MPL. Of these three adjuvants, only alum and MPL havebeen used in vaccines licensed by the U.S. Food and Drug Administration (FDA).Alum was first introduced in the 1930s and MPL, the first and only toll-likereceptor (TLR) ligand currently approved in a human vaccine, was approved 80years later.
The paucity of licensed adjuvants can be explained in partby the fact that they do not receive FDA approval as stand-alone products, butrather as part of a registered vaccine adjuvant-antigen combination. In other words, both the adjuvant andthe antigen components of a vaccine must prove safe and effective together fora successful registration. Further, since most preventative vaccines are forprophylactic use in infants or children, more complex safety considerationshave slowed adjuvant development. However, these considerations may be less ofan issue in the (adult) cancer setting for therapeutic vaccines targetinglife-threatening illnesses.
The new generation immunologic adjuvants have the addedbenefit of reducing the amount of antigen and/or number of vaccine dosesneeded, thus potentially lowering costs to patients and payers. Thisantigen-sparing benefit of adjuvants could allow for the expansion of vaccinesupply to meet the necessary global demands during a pandemic. Such interestsare supported by grants from the Biomedical Advanced Research and DevelopmentAuthority (BARDA), part of the U.S. Department of Health and Human Services. Ifan influenza pandemic were to occur, such as the 2009-10 H1N1 pandemic, thepotential vaccine supply using the old adjuvant technologies would fall severalbillion doses short of the amount needed to provide protection to the globalpopulation.
This is an exciting time in the field of vaccinedevelopment. Just as the approval of rituximab (Rituxan by Biogen) in 1997 wasa watershed event for therapeutic monoclonal antibodies, the pathway for cancervaccines and new generation cancer immunotherapeutics has been opened with therecent FDA approval of Dendreon's Provenge and Bristol-Myers Squibb's Yervoy.The critical enablers of new generation targeted vaccines are adjuvants – anessential part of effective vaccines for the prevention and treatment of manyof the serious diseases for which effective and safe therapies simply do notexist today.