TY - JOUR
T1 - Are anticapsular antibodies the primary mechanism of protection against invasive pneumococcal disease?
AU - Lipsitch, Marc
AU - Whitney, Cynthia G.
AU - Zell, Elizabeth
AU - Kaijalainen, Tarja
AU - Dagan, Ron
AU - Malley, Richard
PY - 2005/4/7
Y1 - 2005/4/7
N2 - Background: Antibody to capsular polysaccharide has been the basis of several vaccines that offer protection against invasive disease from Streptococcus pneumoniae. The success of such vaccines has led to the inference that natural protection against invasive pneumococcal disease is largely conferred by anticapsular antibody. If this is so, one would expect that the decline in disease from different serotypes would vary significantly, and that the appearance of substantial concentrations of anticapsular antibodies would coincide temporally with the decline in age-specific incidence. Methods and Findings: Using incidence data from the United States, we show that, on the contrary, the decline in incidence with age is quite similar for the seven most important serogroups, despite large differences in exposure in the population. Moreover, only modest increases in antibody concentration occur over the second and third years of life, a period in which serotype-specific incidence declines to less than 25% of its peak. We also present detailed data on the distribution of antibody concentrations in Israeli toddlers, which are consistent with the United States findings. The same conclusion is supported by new data on age-specific incidence in Finland, which is compared with published data on antibody acquisition in Finnish toddlers. Conclusion: We suggest some additional studies of the mechanisms of protection that could distinguish among potential alternative mechanisms, including acquired immunity to noncapsular antigens, maturation of nonspecific immune responses, or changes in anatomy or exposure.
AB - Background: Antibody to capsular polysaccharide has been the basis of several vaccines that offer protection against invasive disease from Streptococcus pneumoniae. The success of such vaccines has led to the inference that natural protection against invasive pneumococcal disease is largely conferred by anticapsular antibody. If this is so, one would expect that the decline in disease from different serotypes would vary significantly, and that the appearance of substantial concentrations of anticapsular antibodies would coincide temporally with the decline in age-specific incidence. Methods and Findings: Using incidence data from the United States, we show that, on the contrary, the decline in incidence with age is quite similar for the seven most important serogroups, despite large differences in exposure in the population. Moreover, only modest increases in antibody concentration occur over the second and third years of life, a period in which serotype-specific incidence declines to less than 25% of its peak. We also present detailed data on the distribution of antibody concentrations in Israeli toddlers, which are consistent with the United States findings. The same conclusion is supported by new data on age-specific incidence in Finland, which is compared with published data on antibody acquisition in Finnish toddlers. Conclusion: We suggest some additional studies of the mechanisms of protection that could distinguish among potential alternative mechanisms, including acquired immunity to noncapsular antigens, maturation of nonspecific immune responses, or changes in anatomy or exposure.
UR - http://www.scopus.com/inward/record.url?scp=15744392526&partnerID=8YFLogxK
U2 - 10.1371/journal.pmed.0020015
DO - 10.1371/journal.pmed.0020015
M3 - Article
C2 - 15696204
AN - SCOPUS:15744392526
SN - 1549-1277
VL - 2
SP - 62
EP - 68
JO - PLoS Medicine
JF - PLoS Medicine
IS - 1
M1 - e15
ER -