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-ω-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.