Beaker bytes
A better pneumococcal vaccine?
U.S. infants routinely get shots against Streptococcus pneumoniae, preventing many bacteremia, pneumonia and ear infections. The vaccine, Prevnar, works by eliciting antibodies against the seven pneumococci most common in the U.S. But there's evidence that its use may cause an increase in infections from non-vaccine strains, reducing its effectiveness. And Prevnar doesn't work against many strains in developing countries, where over a million children die annually from pneumococcal infections.
Richard Malley, MD, of Children's Hospital Boston's Division of Infectious Diseases, and colleagues have discovered, surprisingly, that protection against pneumococcus may occur even in the absence of antibodies to the bug's outer capsule. Studying unvaccinated toddlers, they found that the incidence of invasive pneumococcal disease from all strains fell by nearly half between ages 1 and 2, yet antibody levels rose only slightly, arguing for a different protective mechanism. In the lab, the researchers elicited lasting immunity in mice by exposing them to live pneumococci or to a whole-cell vaccine developed by Malley and Porter Anderson, PhD (formerly of Children's). Exposure to one pneumococcal strain made the mice immune to many, apparently through an effect on their CD4+ T cells, specialized white blood cells that regulate immune response.
Malley hopes these findings will garner support for his vaccine or derivatives of it. The vaccine, made of killed pneumococcal cells, would be well suited for developing countries: it is relatively inexpensive, covers a broad range of pneumococcal strains, can be given without needles and doesn't need refrigeration.
Guiding nerve fibers where they need to go
During development of the nervous system, billions of neurons must migrate to the appropriate locations in the brain and grow the nerve fibers, or axons, that connect them with each other. Structures called growth cones steer the axons in the right direction, guided by signals from cells they meet along the way. Some signals lure the axons to extend and grow in that direction; others are inhibitory, making the axon turn away or stop growing.
In two studies in Neuron, researchers from Children's Hospital Boston's Neurobiology Program reveal how one important inhibitory signal, a protein called ephrin, influences axons' growth trajectories. A study led by Christopher Cowan, PhD, and graduate student Yu Raymond Shao showed that ephrin activates a protein called Vav in the axon's growth cone, triggering reactions that repel the axon and make it turn away. The other study, led by Mustafa Sahin, MD, PhD, showed that ephrin also modifies a protein called ephexin, causing the growth cone to physically collapse, steering the axon in a new direction or halting its growth entirely.
Michael Greenberg, PhD, director of the Neurobiology Program and senior investigator on both studies, believes that blocking these inhibitory pathways could allow damaged axons to regenerate and restore nerve function—normally impossible in a mature nervous system. "The pathways we've uncovered could provide opportunities to develop therapies for spinal cord injury," he speculates.
