New Insights Could Lead To A Better Pneumococcal Vaccine

The discovery of a previously unknown mechanism of immunity may lead to a better way to protect vulnerable children and adults against Streptococcus
pneumoniae (pneumococcal) infection. These are the conclusions by researchers from Children's Hospital Boston, the Harvard School of Public Health
(HSPH), the University of Bristol, United Kingdom, the University of Pittsburgh, Göteborg University, Sweden, and the Cambridge Health Alliance,
Cambridge Massachusetts.



The findings, now published in the open-access journal PLoS Pathogens, may aid the development of novel pneumococcal vaccines that would be less
expensive and cover a greater number of known pneumococcal strains than that currently available.



Pneumococcus causes serious infections in children and the elderly, including pneumonia and meningitis (inflammation of the brain). Since 2000, U.S.
infants have been routinely immunized against pneumococcus, but most developing countries (where nearly one million children die from pneumococcal
infections annually) cannot afford the existing vaccine.



Richard Malley, MD, of Children's Division of Infectious Diseases, and Marc Lipsitch, D. Phil., of the HSPH have been studying how natural immunity
against pneumococcus develops, and have shown that in addition to antibodies, T-cells can provide broad protection against this pathogen. In this new
study, Malley and Lipsitch identify the specific protective T-cells - so-called TH17 cells - and show that they protect against infection by
releasing IL-17, a protein that enables human blood cells to kill pneumococcus in the nose more efficiently. This is significant, since colonizing a
person's nose is the first necessary step of infection.



Researchers knew that as children get older, they carry pneumococcus in the nose for shorter periods of time and have less risk of disease, but it
hadn't been known how this resistance develops. Malley, Lipsitch and their colleagues now show that adults and older children, but not newborn
babies, have TH17 cells that target pneumococci, suggesting that exposure to pneumococcus normally leads to production of these cells. In mice, they
show directly that exposure to pneumococcus triggers the development of these T cells and shortens the duration of nasal carriage of the pathogen.



The investigators also describe an efficient way of measuring TH17 cells, which could help determine whether a new vaccine is rallying an effective
response.



"We are now evaluating vaccine candidates and changing them so they not only induce antibodies, but also induce this specific type of immunity,"
says Malley. "A vaccine that induces both protective antibodies and T-cell immunity to pneumococcus may be a very effective way to protect against
this potentially devastating disease."




"Interleukin-17A Mediates Acquired Immunity to Pneumococcal Colonization."
Lu Y-J, Gross J, Bogaert D, Finn A, Bagrade L, et al. (2008)

PLoS Pathog 4(9): e1000159. doi:10.1371/journal.ppat.1000159

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