Burden of
pneumonia caused by
Streptococcus pneumoniae remains high despite the availability of
conjugate vaccines . Mucosal
immunization targeting the
lungs is an attractive alternative for the induction of local
immune responses to improve
protection against
pneumonia . Our group had previously described the development of poly(
glycerol adipate-co-omega-pentadecalactone) (
PGA -co-PDL) polymeric
nanoparticles (NPs) adsorbed with Pneumococcal
surface protein A from clade 4 (PspA4Pro) within
L-leucine microcarriers (
nanocomposite microparticles-NCMPs) for mucosal delivery targeting the
lungs (NP/NCMP PspA4Pro). NP/NCMP PspA4Pro was now used for
immunization of
mice . Inoculation of this formulation induced anti-PspA4Pro
IgG antibodies in
serum and
lungs .
Analysis of binding of
serum IgG to intact
bacteria showed efficient binding to
bacteria expressing PspA from clades 3, 4 and 5 (
family 2), but no binding to
bacteria expressing PspA from clades 1 and 2 (
family 1) was observed. Both mucosal
immunization with NP/NCMP PspA4Pro and
subcutaneous injection of the
protein elicited partial
protection against intranasal lethal pneumococcal challenge with a
serotype 3
strain expressing PspA from clade 5 (PspA5). Although
similar survival levels were observed for mucosal
immunization with NP/NCMP PspA4Pro and subcutaneous
immunization with purified
protein , NP/NCMP PspA4Pro induced earlier control of the
infection . Conversely, neither
immunization with NP/NCMP PspA4Pro nor subcutaneous
immunization with purified
protein reduced bacterial burden in the
lungs after challenge with a
serotype 19F
strain expressing PspA from clade 1 (PspA1). Mucosal
immunization with NP/NCMP PspA4Pro targeting the
lungs is thus able to induce local and systemic
antibodies , conferring
protection only against a
strain expressing PspA from the homologous
family 2.