LONDON ¿ Vaccines that are not completely effective could do more harm than good, a mathematical model developed by population biologists suggests. By allowing pathogens that would normally die out to survive, vaccines such as those being developed for malaria could help more virulent organisms to evolve, which could result in higher death rates among people who remained unvaccinated.
To overcome this problem, scientists should focus on developing vaccines that have several different modes of action, the researchers suggest. The team, from the Institute of Cell, Animal and Population Biology at the University of Edinburgh in the UK, reports the details of the model in a letter to Nature titled ¿Imperfect vaccines and the evolution of pathogen virulence.¿
Andrew Read, a professor of natural history at the Institute of Cell, Animal and Population Biology and senior author of the paper, told BioWorld International that he is greatly in favor of the development of vaccines against malaria.
¿The importance of our model,¿ he added, ¿is that it suggests ways of mitigating the risks of imperfect vaccines. If someone said they had a very good vaccine for malaria, which protects individuals but does not kill the parasite, I would say, go ahead and use it, but be aware that at some time in the future you are going to have trouble. It will give you a window of opportunity, but don¿t be complacent; you need to keep on developing other means of control.¿
Read said there was some evidence that increasing virulence of the virus that causes Marek¿s disease in chickens had resulted from use of similarly imperfect vaccines. He said: ¿These vaccines seem to be good for about 10 years, but then researchers have to design something better. It looks as though what our models suggest would happen in malaria has already happened in Marek¿s disease.¿
Read and his team have been working on malaria for about a decade, studying the factors that influence whether parasites become more or less virulent. They realized that vaccines could help shape the evolution of virulence.
Conventional wisdom suggests that excessively virulent parasites are removed from the population because they kill their hosts. If the host has been vaccinated using a vaccine that boosts the immune system enough to prevent death, but allows the parasites to survive, for example, then more virulent parasites can be passed on to others.
Vaccines against malaria are unlikely to be highly effective because natural immunity to this disease is weak and, Read said, no vaccine to it has ever generated immunity that is any stronger than the weak natural immunity.
The group¿s paper in Nature provides a mathematical simulation of what would happen to the epidemiology of the disease in the event that vaccines of various types become available. The paper considers four types of malaria vaccine. Infection-blockers will stop someone from becoming infected in the first place. Antigrowth-rate vaccines aim to stop the parasite replicating in the bloodstream. Antitransmission vaccines prevent the parasite from being transmitted to its next host, the mosquito. Finally, antitoxin vaccines prevent the parasites from harming their human host, but do not kill the parasites.
¿What our paper shows in general, and for malaria in particular, is that the antitoxin vaccine and the antigrowth-rate vaccine will both lead to increasing virulence of the parasites, increasing the long-term risk for unvaccinated individuals. In the malaria model, this seems to take three to four decades,¿ Read said.
The team is planning some experimental work using a mouse model of malaria, including an assessment of how host genotype influences the model.
Writing in Nature, Read and his colleagues conclude: ¿With antigrowth-rate, antitoxin and transmission-blocking vaccines, evolution toward higher virulence erodes the overall benefits of vaccination. In contrast, when anti-infection vaccines are used, evolution toward lower virulence may increase the population-level benefits of vaccination. At high vaccination coverage, a vaccine that incorporates all four types of vaccines would be the most efficient, even when evolution occurs. This result supports the development of multivalent, multistage vaccines which, it is hoped, will provide greater overall protection than single-target vaccines.¿