N. Srivastava et al., Selection of an immunogenic and protective epitope of the PsaA protein of Streptococcus pneumoniae using a phage display library, HYBRIDOMA, 19(1), 2000, pp. 23-31
Streptococcus pneumoniae is an important pathogen that causes disease in yo
ung and elderly individuals. The currently available polysaccharide vaccine
s have limited efficacy in those age groups most susceptible to pneumococca
l infections. This study focuses on mapping the epitopes of a surface prote
in of S, pneumoniae by biopanning a 15 mer phage display library using 5 di
fferent monoclonal antibodies (MAbs) against the Pneumoccal surface adhesin
A (PsaA). PsaA is a component of the bacterial cell wail that is highly sp
ecies specific and is involved in bacterial adherence and virulence. Biopan
ning of the phage display library reveals three distinct epitopes on the Ps
aA protein, The sequence homology of these epitopes ranges from two to six
amino acids when compared to the native PsaA protein type 2. Two of these e
pitopes have been evaluated for their immunogeneicity in mice. The peptide
selected by the MAbs 8G12, 6F6, and 1B7 is referred to as the consensus pep
tide and is immunogenic in mice. Optimal anti-PsaA response is observed in
mice immunized with 50 mu g of the consensus peptide complexed to proteosom
es in 1:1 ratio. The anti-PsaA response is significantly lower than the res
ponse to the PsaA native protein. The peptide selected by monoclonal antibo
dy 4E9 in its lipidated form is significantly protective in mice challenged
with S, pneumoniae serotype 2 when compared to mice immunized with the nat
ive protein. These results show that the selected epitopes of PsaA protein
are immunogenic and protective in mice. These epitopes need to be evaluated
further as alternatives to currently available vaccines.