Before the advent of the pneumococcal vaccine, known as Prevnar, S. pneumoniae caused millions of ear infections each year, half a million episodes of bacterial pneumonia, and life- threatening cases of meningitis and bacteremia. Prevnar triggers recipients’ immune systems to produce “anticapsular antibodies.” However, Prevnar doesn’t work well in the developing world, and it is expensive and difficult to manufacture. Moreover, in several studies, use of pneumococcal conjugate vaccines caused non-vaccine strains to become more common, suggesting that Prevnar could eventually become ineffective even in the U.S.

Lipsitch and Malley first conducted epidemiologic studies in unvaccinated toddlers in the U.S., Israel, and Finland, and the incidence of invasive disease from most pneumococcal strains fell by nearly half between one and two years of age. Yet anti- capsular antibody concentrations increased only slightly.

Searching for what caused these results, Malley and Lipsitch were able to elicit long-lasting immunity to pneumococcus in mice independently of any antibodies. When the mice were exposed to live pneumococci, or to a whole-cell vaccine developed in Malley’s lab, they were immune to pneumococcal colonization, regardless of their ability to make antibodies. Moreover, mice exposed to a single pneumococcal strain became immune not just to that strain and others. The immunity appeared to arise from an effect on the immune system’s CD4+ T-cells.

Their findings suggest that while antibodies protect sufficiently against pneumococcal disease, they may not represent the natural mechanism of protection.

The whole-cell vaccine could protect against all pneumococcal strains, Malley says, and would be a boon for the developing world because it is inexpensive, covers all pneumococcal strains, and does not require refrigeration.