It’s fair to say that vaccines haven’t had the best few years in terms of PR. The “anti-vax” movement of parents suspicious about potential side effects of childhood vaccines has grown in strength, despite numerous studies proving their fears to be foundless. Certain high-profile diseases, such as HIV, have repeatedly proven resistant to traditional vaccine approaches. Meanwhile, vaccines suffer somewhat from their own incredible success – with many of the diseases that once caused rampant child mortality now under control or eradicated, one might think that the tool has maxed out its potential.
But two talks on Wednesday at the University of Chicago suggested that the age of vaccines is far from over. A revolution in the scientific approach to creating vaccines has begun to yield promising new strategies for controlling previously stubborn diseases, such as meningococcus and MRSA. Those advances have also made vaccines safer than ever, eliminating even the small risk inherent in the vaccines used early in the 20th century. As scientists move on to tackling diseases of adolescence, adulthood and developing countries, the ability of vaccines to change the world is only growing, said Rino Rappuoli, global head of vaccines research at Novartis Vaccines and Diagnostics.
“Most people say the last century of vaccines has been very positive: they eliminated polio, they eliminated diptheria and tetanus – what are you going to now, are you out of a job?,” said Rappuoli, who delivered the 2010 George & Marie Andros Lecture. “But I believe, in the 21st century, vaccines are going to be as important, and maybe more important, than they were in the 20th century.”
Until the late 1970’s, Rappuoli said, the strategy for creating new vaccines was largely the same as the approach developed by Louis Pasteur nearly one hundred years prior: Isolate, Inactivate, Inject. Pasteur learned that exposing a person to a non-toxic version of a disease-causing bacterium or virus sensitized their immune system, such that subsequent exposures to the true pathogen were fought off. That strategy led to vaccines for smallpox, measles, diptheria, mumps, polio and many other diseases that were once a scourge upon young children.
Nevertheless, several diseases remained unpreventable with this traditional vaccine approach, frustrating the field. Then, like many other scientific areas, new hope arrived in the form of genomics, which made a new form of vaccine research possible, Rappuoli said. With genomics, scientists developed reverse vaccinology, the process of sequencing a bacterial or viral genome to find components of the pathogen that are promising as “protective antigens” in a vaccine. Rappuoli discussed the first success of this method – the creation of a vaccine for meningococcus, which was given to all children under the age of 18 in the UK in 2000.
“The genome approach and the biology approach combine together and very frequently can bring you to a new, potential vaccine,” Rappuoli said. “These things were not possible before the genome. It would have taken one scientist a lifetime to develop.”
Another example of reverse vaccinology is taking place right now in the laboratory of Olaf Schneewind, professor and chair of microbiology at the University of Chicago Medical Center. Schneewind’s project to develop a vaccine for Staphylococcus aureus, the bacteria that causes hospital- and community-acquired MRSA, was discussed both by Rappuoli and Schneewind himself, at a midday seminar to the MacLean Center for Clinical Medical Ethics. As described by Schneewind, Staph aureus is a particularly dangerous foe: the leading cause of blood, skin and soft tissue infections, with a mortality that exceeds that of HIV/AIDS. The bacterium has also proved difficult for vaccine researchers, as unlike other pathogens, a Staph aureus infection does not confer immunity to subsequent infections.
“Immunologically speaking, organisms learn nothing about disease protection from this process,” Schneewind said. “These organisms are the world champion of immunosuppression; it’s really remarkable how well it works.”
But through genetic analysis, Schneewind’s laboratory has found four potential antigens that may trigger the immunologic memory necessary for protection. The key may lie in creating a non-toxic form of a Staph aureus component called Protein A, which normally allows the bacteria to trick the immune system into suppressing its defenses. A vaccine based on Schneewind’s strategy is close to clinical trials, funded by Novartis.
The Staph aureus vaccine and many others in development inspire Rappuoli’s optimism about the future of the field. By developing new protections against diseases of adulthood, Rappuoli predicted an important role for vaccines in our “aging society” of longer life expectancy, even envisioning a future where 55-year-olds receive as many vaccines as infants. And by developing more vaccines for diseases of the developing world – an area that has previously been “the biggest frustration of my entire career,” Rappuoli said – the field has an opportunity to fight world poverty by reducing the burden of illness in poor populations. The Novartis Vaccines Institute for Global Health, a non-profit organization founded by Rappuoli in 2007, will reach a landmark in that effort this week as they administer the first injections of a new vaccine against the salmonella bacteria that causes typhoid fever.
“I like to call vaccines the life insurance of the 21st century,” Rappuoli said. “That’s the power of vaccination.”