Vaccine-induced human antibodies to PspA augment complement C3 deposition on Streptococcus pneumoniae

Abstract

Pneumococcal surface protein (PspA) is a virulence factor expressed by all clinical isolates of Streptococcus pneumoniae. PspAs are variable in structure and have been grouped into clades and cross-reacting families based on sequence similarities and immunologic cross-reactivity. At least 98% of PspAs are found in PspA families 1 or 2. PspA has been shown to interfere with complement deposition on pneumococci, thus reducing opsonization and clearance of bacteria by the host immune system. Prior studies using pooled human sera have shown that PspA interferes with C3 deposition on a single strain of S. pneumoniae, WU2, and that mouse antibody to PspA can enhance the deposition of C3 on WU2. The present studies have demonstrated that these previous findings are representative of most normal human sera and each of seven different strains of S. pneumoniae. It was observed that PspAs of PspA families 1 and 2 could inhibit C3 deposition in the presence of immunoglobulin present in all but 3 of 22 normal human sera. These studies have also demonstrated that rabbit and human antibody to PspA can enhance the deposition of C3 on pneumococci expressing either family 1 or 2 PspAs and either capsular types 2, 3, or 11. A vaccine candidate that can elicit immunity that neutralizes or compensates for S. pneumoniae's ability to thwart host immunity would be of value.

Phenotypic and Molecular Characterization of Optochin-Resistant Streptococcus pneumoniae Isolates from Brazil, with Description of Five Novel Mutations in the atpC Gene

“…1). These results show that distribution of pspA gene families among Opt r S. pneumoniae strains follows a profile quite similar to that seen among S. pneumoniae isolates in general, with predominance of pspA families 1 and 2 (38). Moreover, Opt s subpopulations derived from heterogeneous cultures showed PFGE profiles, MLVA types, and pspA gene family types identical to those of their respective Opt r counterparts.…”

Molecular Dissection of Antibody Responses against Pneumococcal Surface Protein A: Evidence for Diverse DH-Less Heavy Chain Gene Usage and Avidity Maturation

“…PspA has been shown to elicit high Ab levels in humans (11), and human anti-PspA serum Abs can protect mice against challenge with virulent pneumococcal strains when transferred (12). Recently, vaccine-induced human Abs to PspA has been shown to augment complement component C3 deposition on S. pneumoniae (13).…”

A Bivalent Vaccine Based on a Replication-Incompetent Influenza Virus Protects against Streptococcus pneumoniae and Influenza Virus Infection

“…As to protection from S. pneumoniae infection, the induction of anti-PspA antibodies is considered a promising strategy. Anti-PspA antibodies disable PspA function, which inhibits the complement deposition on the bacterial surface (12,13,28) and can facilitate bacterial clearance by opsonization-mediated phagocytosis. Thus, HA-KO/PspA virus could provide mice with protective immunity against S. pneumoniae as well as influenza virus infection.…”

“…PspA is found in all clinical S. pneumoniae isolates (11). Some studies have demonstrated that antibodies against PspA neutralize the anticomplement effect of PspA, which results in clearance of the bacteria by depositing complement C3 on the bacterial surface (12,13). Moreover, anti-PspA antibodies have also been shown to prevent infection from strains with different serotypes (14).…”