Vaccine discovery and translation of new vaccine technology

The second paper in The Lancet Series on the New Decade of Vaccines focuses on vaccine discovery and translation of new vaccine technology. The paper is by Dr Steve Black, Center for Global Health, University of Cincinnati Children's Hospital, Cincinnati, OH, USA, Dr Rino Rappuoli, Novartis Vaccines, Siena, Italy, and Dr Paul Henri Lambert, Centre of Vaccinology, University of Geneva, Switzerland.

In the twentieth century, vaccines have led to massive reductions in the disease scourges of mankind exemplified by the eradication of smallpox in 1980 but also with large reductions in morbidity and mortality due to measles, diphtheria, tetanus, and most recently with the impending eradication of polio. Within the last two decades, new technology including the development of glycoconjugate vaccines against Hib, pneumococcus, and most recently the meningococcus have resulted in virtual eradication of Hib disease in all countries where routine vaccination has been introduced, large reductions in morbidity and mortality due to pneumococcal pneumonia and meningitis, and now the potential to tame meningococcal meningitis and sepsis. For pneumococcal disease alone, vaccination has the potential to prevent more than 1 million deaths a year globally caused by acute lower respiratory tract infections.

Vaccines have also become safer with the introduction of purified component vaccines for pertussis and safer manufacturing procedures for polio and other vaccines. New technologies have resulted in much improved safety profiles and improved effectiveness of vaccines. However, in large part due to the very effectiveness of the vaccines, the memory of the diseases they are designed to prevent has disappeared from public memory and public confidence in vaccines has deteriorated. Further work to educate the public on the benefits of vaccines and the potential for these diseases to return if vaccination levels fall is necessary.

The scope of vaccines has increased with newer vaccines now targeting the prevention of cancer such as the human papillioma virus (HPV) vaccine for the prevention of cervical cancer. Also, better vaccines are being developed for populations such as young children and the elderly which utilise adjuvants to make these vaccines more effective in these disease vulnerable populations. In addition, approaches for the vaccination of pregnant women will allow protection of very young infants against diseases such as group B streptococcal disease during the newborn period. Beyond disease prevention in industrialised countries, efforts of many institutions, including the Hilleman Institute, the Novartis Vaccine Institute for Global Health, and the Bill & Melinda Gates Foundation, can expand the potential of vaccines to the developing world through more rapid development and introduction of vaccines focused on the needs of these countries.

It costs about $US 500 million to bring a new vaccine into the market. New techniques, such as systems biology offer the promise of more efficient identification of safe and effective vaccines which could lower this development cost and thus allow more vaccines to be developed. However, the authors note that "In view of the high cost of vaccine development, the availability of official guidance from regulatory and advisory bodies about recommendations for use of a potential vaccine would allow more efficient and effective prioritisation of vaccines for development."

Challenges for the next decade involve application of new technologies, including molecular genetics and structural biology, to develop vaccines against as yet unpreventable lethal bacterial infections such as meningococcus B and Staphyloccus aureus. Approaches such as "reverse vaccinology" now allow identification of new targets antigens for prevention of disease due to these organisms. In addition, research in human genetics offers the possibility to identify individuals predisposed to poor immune responses or rare adverse events to vaccines and develop specialised approaches for them.

The authors conclude that the 21st century promises to be a fruitful one for the prevention and treatment of disease through vaccination, although many challenges remain.

Professor Steve Black University of Cincinnati Children's Hospital, Cincinatti, OH, USA.T) +39 346 309 2970 E) stevblack@gmail.com

Dr Rino Rappuoli, Novartis Vaccines, Siena, Italy. T) +39 0577 243414 E) rino.rappuoli@novartis.com

Note to editors: *Reverse vaccinology is a process involving screening of the entire pathogenic genome. Next, the genes are filtered for desirable attributes that would make good vaccine targets such as outer membrane proteins. Those proteins then undergo normal wet lab testing for immune responses.