Immunization with PspA Incorporated into a Poly(Ethylene Oxide) Matrix Elicits Protective Immunity against Streptococcus pneumoniae

Abstract

CBA/N mice were immunized with PspA in a poly(ethylene oxide) matrix to examine its ability to deliver the antigen and modulate the immune response. All mice receiving PspA in the matrix survived a lethal pneumococcal challenge and had serum anti-PspA antibody levels statistically higher than mice receiving PspA alone (P < 0.009).

Initial and Subsequent Response to Pneumococcal Polysaccharide and Protein‐Conjugate Vaccines Administered Sequentially to Adults Who Have Recovered from Pneumococcal Pneumonia

“…Depletion of sensitized B-cells or induction of long-lived T regulator suppressor cells may be responsible, and this phenomenon may be an intrinsic property of the response to polysaccharides in adults These results question the long-term value of administering PPV to persons who have recovered from pneumonia. They further reinforce the need to develop protein vaccines for high-risk adults, for example, those derived from pneumolysin, from surface-exposed pneumococcal surface proteins A or C [43], or from other proteins newly recognized by microarray analysis [44, 45] in order to protect our highest risk populations from pneumococcal disease.…”

Pneumococcal Surface Protein A Contributes to SecondaryStreptococcus pneumoniaeInfection after Influenza Virus Infection

“…PspA is well established as both a crucial virulence factor [12, 14–16] and a broadly protective antigen in a variety of immunization and challenge models [17–22]. Given the lower respiratory tract inflammatory response accompanying influenza infection, we hypothesized this virulence factor’s function in inhibiting complement mediated clearance would become critical in a secondary pneumococcal infection.…”

“…Consistent with these results and a unique role for PspA in secondary infections, BALF levels of albumin and LDH were significantly reduced in PspA-immunized groups but not in PBS-treated or CTB-treated controls receiving D39, WU2 or TIGR4 infections following prior influenza infection. Despite substantial sequence variability, both cross-reactivity and protection have been observed between immunized sera and heterologous PspA proteins [17, 41]. The rPspA/Rx1 (family 1, clade 2 and type 25) PspA antigen used in this present study has been shown to induce immune mouse serum cross-reactive with PspA proteins present on D39, WU2 and EF3296 pneumococcal strains [17] where the N-terminal region of the EF3296 PspA protein is identical to that of TIGR4 [42].…”

“…Despite substantial sequence variability, both cross-reactivity and protection have been observed between immunized sera and heterologous PspA proteins [17, 41]. The rPspA/Rx1 (family 1, clade 2 and type 25) PspA antigen used in this present study has been shown to induce immune mouse serum cross-reactive with PspA proteins present on D39, WU2 and EF3296 pneumococcal strains [17] where the N-terminal region of the EF3296 PspA protein is identical to that of TIGR4 [42]. Additionally, it has been shown that immunization with the D39 type 25 PspA can provide protection against lethal challenges with the D39 and WU2 strains and perhaps some, albeit not statistically significant, protection against EF3296 [43].…”

“…PspA is a choline-binding surface protein, which inhibits complement-mediated phagocytosis and binds to and prevents killing by lactoferrin [12, 13]. Numerous studies have documented attenuation in mutants lacking PspA [12, 14–16], and PspA protein is protective in a variety of delivery and challenge models [17–22]. …”