Successful Development of Vaccines

Applied Clinical Trials

Applied Clinical Trials, Applied Clinical Trials-10-11-2005, Volume 0, Issue 0

News broke last week about the initial success of Merck & Co's experimental vaccine to prevent cervical cancer. Gardasil, a genetically engineered vaccine, blocks infection with two types of human papilloma virus, HPV 16 and 18. This development added to the mood of excitement and air of eager anticipation surrounding the 75-minute workshop given by a leading European expert in vaccine trials.

News broke last week about the initial success of Merck & Co's experimental vaccine to prevent cervical cancer. Gardasil, a genetically engineered vaccine, blocks infection with two types of human papilloma virus, HPV 16 and 18. This development added to the mood of excitement and air of eager anticipation surrounding the 75-minute workshop given by a leading European expert in vaccine trials.

Significant progress has been achieved in vaccine development, but additional regulatory, technical, and manufacturing hurdles must be overcome before more compounds can enter routine clinical use, stated Dr. Keith Bragman, a consultant in pharmaceutical development and healthcare.

Public demand for safe and effective vaccines is high, but very few sponsors have the knowledge and facilities to develop and manufacture a new compound. The technology is complex, translating basic science advances into useful vaccines is tough, and manufacturing tens of millions of doses a year is required, he explained.

"The regulatory oversight is much more demanding than those governing the manufacture of either therapeutic proteins or small-molecule pharmaceuticals," said Bragman. "Vaccines are much more difficult to characterize analytically than many pharmaceuticals."

Because vaccines are injected into healthy children and adults, safety is of paramount importance, and this rightly influences every step in the development cycle. A vaccine intended for universal pediatric use requires proof of efficacy and very extensive safety testing. Pharmacovigilance programs are obligatory in Phase III and beyond, but they pose major challenges in poor countries.

In the area of infectious diseases, the involvement of the Bill and Melinda Gates Foundation has been a remarkably positive development, he noted. For example, they contributed $70 million to a public-private effort to develop a new meningitis A conjugate vaccine. Preclinical studies suggest the vaccine is highly immunogenic and stimulates high levels of antibodies, and Phase I trials are due to begin this year. The vaccine was designed by the Center for Biologics Evaluation and Research of the FDA, and the technology was transferred to the Serum Institute of India.

Other targets for vaccine developers include TB, malaria, influenza and the threat of pandemic (avian) flu, biodefense initiatives (smallpox, anthrax, Ebola), and HIV. The latter still represents a formidable challenge, according to Bragman.

For further reading, he recommended the following two web addresses:

WHO, Geneva:
http://www.who.int/mediacentre/factsheets/fs289/en/

Nature:
www.nature.com/nm/journal/v11/n4s/full/nm1218.html