Concentration of antipneumococcal antibodies as a serological correlate of protection: an application to acute otitis media.
BACKGROUND
For the licensing of new pneumococcal vaccines, it is vital to be able to predict their protective efficacy on the basis of immunogenicity. However, the serological correlates of protection have not been established for pneumococcal diseases.


METHODS
A total of 1666 children were immunized with the pneumococcal conjugate vaccine. Acute otitis media (AOM) events were identified, and middle-ear fluid was cultured for pneumococci. The association between the concentration of antibodies against serotypes 6B, 19F, and 23F and the risk of AOM caused by the homologous serotypes or by the cross-reactive serotype 6A was assessed. An association model was used to predict efficacy at different geometric mean concentrations (GMCs).


RESULTS
An association between antibody concentration and risk of AOM was found, but with large differences between serotypes. On the basis of the association, the predicted efficacy for 19F was negligible up to the highest GMC tested. In contrast, 6B was found to be highly efficacious (>65%) at a GMC of 0.5 microg/mL.


CONCLUSIONS
The results challenge the view that a new vaccine candidate should always induce antibody concentrations that are not inferior to those produced by the licensed vaccine. Furthermore, the differences between serotypes caution against defining a common correlate of protection that is applicable to all serotypes.
Jokinen
Jukka T
JT
Department of Vaccines, National Public Health Institute, Helsinki, Finland. jukka.jokinen@ktl.fi
Ahman
Heidi
H
Kilpi
Terhi M
TM
Mäkelä
P Helena
PH
Käyhty
M Helena
MH
D000208:Acute Disease; D000907:Antibodies, Bacterial / Q000097:blood*; D004432:Ear, Middle / Q000382:microbiology; D006801:Humans; D007223:Infant; D010033:Otitis Media / Q000276:immunology / Q000517:prevention & control*; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000008:administration & dosage* / Q000276:immunology
D000907:Antibodies, Bacterial; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate