Vaccines are one of the most successful public health interventions we've developed—a simple injection can lead to a life-long immunity to disease-causing agents. But not every vaccine is so successful; for a number of agents, regular booster shots are needed to prevent immunity from fading. But researchers are starting to look into a possible route around this problem: a self-boosting vaccine. The challenge will be making one that's safe and acceptable to the public.

Immunity works because some of the cells that recognize pathogens we're exposed to get set aside as "memory" cells. When the pathogen reappears, these cells are able to rapidly mobilize an assault on the invader, clearing it before it can even cause much in the way of symptoms. But some pathogens never manage to set off a full-intensity immune response, and the resulting memory gradually fades. To maintain immunity, sporadic re-exposures (either to the pathogen or another dose of vaccine) are needed. But, as with many other things, adults have a habit of forgetting these shots or putting them off.

But a paper published in PNAS earlier this week made me aware that researchers are now looking at ways to avoid the requirement for extra shots. A self-boosting vaccine would, with a single dose, give people regular re-exposure to the proteins of dangerous infectious agents possibly handling several risks with a single dose. The downside? The method would involve giving the vaccine's recipients a lifelong viral infection.

Of course, many people already have these infections. Herpes viruses and cytomegalovirus often set up shop in human cells without causing any symptoms for years. But they also sporadically come out of hiding (rather famously in the case of the herpes family) and start a brief flare up. Although the immune system can clear the active infection, it never manages to eliminate the reservoir of quiescent virus hiding out in some cells.

In many ways, this is exactly the sort of behavior that a self-boosting vaccine would need. The sporadic activity would re-expose the immune system to any proteins carried by the virus. Since these viruses have very large genomes to start with, it would be relatively simple to engineer in additional genes without interfering with its normal cycle. In fact, it should be possible to engineer in proteins from multiple viruses, with a single vaccine providing life-long exposure to a variety of threats.

That's all on the positive side. The negative sides, however, are very substantial. Cytomegalovirus doesn't normally cause symptoms in healthy people, but it tends to be active in very young babies and among those with immune defects, where it can cause serious complications. Herpes viruses cause unpleasant symptoms as well. Plus, with public acceptance of vaccines having issues at the moment, convincing people that they should voluntarily get infected with one might be a very hard sell.

Obviously, the goal will be to develop attenuated versions of the viruses that are much less likely to re-activate in a way that produces any symptoms. But it can't be so attenuated that it never reactivates, or it wouldn't accomplish the whole goal of the vaccine: re-exposure to the proteins it encodes. And, right now, we don't really have a strong grasp on precisely what leads the virus to be reactivated in the first place.

The PNAS paper that pointed me towards the idea also highlights another issue with this approach to vaccination: it could change the dynamics of the herd immunity we currently rely on for public health. The paper modeled the pathogen pertussis, which children receive vaccinations against, but adults need continued boosting. Because the pathogen is still circulating at low levels, a population contains a complicated mix of people: unvaccinated, partly immune, etc. As a result, the pathogen itself helps keep immunity high by exposing some of the unvaccinated and giving others a boost without causing any symptoms.

In their model, the researchers found that the self-boosting vaccine changed the dynamics of herd immunity. Those that were vaccinated, of course, never had to worry again. But this cut down the circulation of the pathogen in general, meaning that the unvaccinated were less likely to ever get exposed. That actually led to increased disease incidence among the unvaccinated.

In any case, we're still a long way off from developing these self-boosting vaccines. But it's a clever idea that could lead to a dramatic change in the dynamics of disease prevention.

PNAS, 2012. DOI: 10.1073/pnas.1209683109 (About DOIs).