Producers aim much R&D at targets such as Ebola and HIV for which no vaccine exists
Vaccine research has a long history, dating back to Edward Jenner’s first inoculation against smallpox in 1796. But today the field is growing vigorously, propelled by a rising world demand to fight existing diseases and to guard against new threats. The technology of vaccine development and production is advancing rapidly.
“The nature of vaccines means that they usually work quietly in the background through a person’s life — so quietly that in some parts of the world people are forgetting how important vaccines are,” says Rajeev Venkayya, president of the global vaccine business unit at Takeda, the pharmaceutical company. “Many exciting innovations” are extending vaccines’ reach, he adds.
Takeda is pushing its own reach beyond Japan, where it has been making vaccines for 70 years, in an effort to become a global supplier. This month it completed enrolment of 20,100 children in Latin America and Asia for a large-scale clinical trial of its new vaccine against dengue, an important public health problem in the tropics.
The world vaccines market is worth about $35bn a year and growing in value by at least 8 per cent annually. The “big four” vaccine companies, GSK of the UK, Merck and Pfizer of the US and Sanofi of France, account for 80 per cent of global vaccine revenues, says a new Access to Vaccines Index issued by the Access to Medicines Foundation, an independent Dutch body.
The index has analysed the industry’s research and development pipeline, including the big four and four other challengers (Johnson & Johnson, Daiichi Sankyo, Takeda and Serum Institute of India). It found that altogether the eight companies were working on 89 vaccine R&D projects for 35 diseases.
About half the projects are efforts to improve existing vaccines, for example by changing formulation or production method. Half are developing innovative products. The foremost research targets are meningococcal and pneumococcal disease, influenza, respiratory syncytial virus (RSV) and human papillomavirus (which causes cervical cancer).
The World Health Organization lists about 30 diseases for which vaccines are commercially available. The Access to Vaccines Index notes about a third of R&D projects target important diseases for which no vaccine exists, including viruses such as Ebola and HIV and bacteria such as streptococcus, staphylococcus, E. coli and C. difficile. The greatest public health need is probably a vaccine against HIV to stem the Aids pandemic. Dozens of corporate and academic labs have poured resources into HIV vaccine R&D since the virus was identified in the 1980s as the cause of Aids, without much success.
Mark Feinberg, chief executive of the International Aids Vaccine Initiative, a public-private partnership, says: “The development of an HIV vaccine is probably the greatest challenge that biomedical science has taken on in the public health arena.” HIV is more problematic than other viruses: it mutates rapidly and exists in many different genetic strains, undermines the host’s immune system and buries itself deep within human cells for an indefinite period.
A large trial is getting under way in South Africa of an experimental vaccine called HVTN 702, an improved version of a treatment that showed modest efficacy in an earlier clinical study in Thailand. More than 5,400 HIV-negative volunteers will receive HVTN 702 or a placebo. Researchers will compare infection rates between the two groups.
Scientists do not expect HVTN 702 to show the high levels of efficacy that characterise most commercial vaccines. But a recent big US study of the future course of the pandemic, funded by the National Institutes of Health and carried out by Oregon State University and Yale School of Public Health, showed that even a vaccine that is just 50 per cent effective could have a big impact.
Such a vaccine introduced in 2020, say, could prevent 17m new HIV infections over the next 20 years and reverse the pandemic’s course, the study found. “HIV and Aids are still nowhere near being under control,” says Jan Medlock, lead author of the study, published in the Proceedings of the National Academy of Sciences journal. “This problem is still getting worse, not better, and our research shows the value of prospective vaccines could be very significant.”
Rino Rappuoli, chief scientist at GSK vaccines, has been working on HIV for 20 years. “I believe we’re going to get there,” he says. “It is impossible to control HIV without a vaccine.” His colleague Rip Ballou, head of GSK’s US vaccines R&D centre in Rockville, Maryland, observes that their development “is as much luck as science. Most vaccines we have today are a great idea that happened to work out,” he says. “We’re making a lot of progress but I think we need to understand the rules of the immune system better.”
One area yielding results is vaccines tailored for older people whose immune systems are less responsive than the children and teenagers who are the main recipients of traditional vaccines. An example is GSK’s new Shingrix vaccine against varicella zoster. The virus causes chickenpox in early life, remains inactive in the body and re-emerges in middle or old age to cause painful shingles. “Improvements in making the immune system more responsive to vaccination” have made Shingrix possible, says Dr Ballou.
Technology moves forward on many fronts. One is the wave of RNA and DNA vaccines in development. Many of these advances are coming out of universities and smaller biotechnology companies.
Prokarium, a UK company with facilities in London and Keele in Staffordshire, has developed vaccines that can be taken by mouth and be stored for weeks at room temperatures without the costly refrigeration needed for conventional vaccines.
The company’s technology involves swallowing a capsule that passes through the stomach to the intestine, where it releases salmonella bacteria engineered to produce vaccine safely from inside the body’s own immune cells — just where it is needed. Tested on 500 volunteers including 100 children, it is potentially applicable to a wide range of vaccines, says Ted Fjallman, Prokarium chief executive. Early candidates include typhoid and several bacteria that cause diarrhoea.
“Our technology avoids the need for injections with a needle,” he adds, and can be delivered to people in remote poor areas, “as the vaccine is stable at high temperatures and can be manufactured for about one-third of the price of conventional injectable vaccines”.
By Clive Cookson