Since 2000, U.S. infants have been routinely immunized against pneumococcal (Streptococcus pneumoniae) infection. Now, Boston researchers have made a surprising discovery about natural immunity to pneumococcus.
Two related studies, led by Dr. Richard Malley of the Children's Hospital Boston Division of Infectious Diseases and Dr. Marc Lipsitch of the Harvard School of Public Health, suggest that natural protection from pneumococcal disease may derive from some previously unrecognized immune mechanism, which could possibly be exploited for a new vaccine. The latest study appears in the current (March 29) issue of the Proceedings of the National Academy of Sciences.
In the U.S., before the advent of the pneumococcal conjugate vaccine, known as Prevnar, S. pneumoniae caused more than 7 million ear infections each year, half a million episodes of bacterial pneumonia, and life-threatening cases of meningitis and bacteremia.
Prevnar is made up of material from the outer capsule of each of the seven pneumococcal strains most common in the U.S. This material triggers recipients' immune systems to produce so-called anticapsular antibodies specific to those strains.
However, Prevnar doesn't work against many pneumococcal strains in the developing world, where pneumococcus kills nearly 1 million children annually, and it is expensive and difficult to manufacture, leading to chronic shortages. Moreover, in several studies, use of pneumococcal conjugate vaccines caused non-vaccine strains to become more common, raising concerns that Prevnar could eventually become ineffective even in the U.S. Of 90 known pneumococcal strains, Prevnar only covers seven.
Lipsitch and Malley first conducted epidemiologic studies in unvaccinated toddlers in the U.S., Israel, and Finland. As they reported in January in the online journal PLoS Medicine, the incidence of invasive disease from almost all pneumococcal strains fell by nearly half between 1 and 2 years of age. Yet, anti-capsular antibody concentrations increased only slightly, suggesting that a mechanism other than antibody to the pathogen's outer capsule may be conferring natural protection against pneumococcal disease.
What then might provide this protection? Looking at the first step of pneumococcal disease, colonization of the nose and throat, Malley and Lipsitch were able to elicit long-lasting immunity to pneumococcus in mice independently of any antibodies. In the current (March 29) Proceedings of the National Academy of Science, they report that when mice were exposed to live pneumococci, or to a whole-cell vaccine developed in Malley's lab, they were highly immune to pneumococcal colonization -- even if they were genetically unable to make antibodies. Moreover, mice exposed to a single pneumococcal strain became immune not just to that strain, but to others. The immunity appeared to arise from an effect on the immune system's CD4+ T-cells, since mice that lacked these cells did not develop immunity.