Trends in Microbiology
Novel pneumococcal surface proteins: role in virulence and vaccine potential
Section snippets
Pneumococcal common protein vaccine antigens
In view of the above, much recent attention has focused on the possibility of developing vaccines based on pneumococcal protein antigens common to all serotypes. Such proteins, being T-cell-dependent antigens, are likely to be highly immunogenic in human infants and, moreover, to elicit immunological memory. So far, two candidate pneumococcal common protein antigens have been investigated in detail. The first is pneumolysin, a potent thiol-activated cytolysin, which is produced by virtually all
Other pneumococcal choline-binding proteins
The choline-binding repeat domain is not unique to PspA and is also found in the major pneumococcal autolysin(LytA), which has six copies of the repeat unit in its carboxy-terminal region[5]. McDaniel et al.[9]have also demonstrated the presence of at least one other S. pneumoniae gene, which hybridizes at high stringency with probes specific for the 3′ half of pspA. At lower stringency, several other genes hybridize, including lytA, indicating that a family of pneumococcal surface proteins
Pneumococcal surface adhesin A (PsaA)
PsaA is another pneumococcal surface protein worthy of consideration for inclusion in a protein-based vaccine. It was initially thought to be an adhesin, based on sequence homology with putative lipoprotein adhesins of Streptococcus sanguis and Streptococcus parasanguis[13]. PsaA and the related streptococcal proteins all contain the prolipoprotein recognition sequence LXXC at the carboxyl end of their signal peptides, which might suggest that the amino terminus is closely associated with the
Conclusions
Of the pneumococcal proteins proposed as vaccine candidates to date, pneumolysin, PspA and PsaA have all been shown to contribute to the virulence of S. pneumoniae and to be produced by virtually all clinical isolates. Moreover, for pneumolysin and PsaA, there appears to be no significant antigenic variation from isolate to isolate, and PspA contains cross-protective epitopes despite variation in the amino-terminal region. The likely role of CbpA as a mediator of nasopharyngeal colonization
References (16)
Trends Microbiol.
(1996)Microb. Pathog.
(1992)Microb. Pathog.
(1996)Infect. Immun.
(1994)Infect. Immun.
(1990)J. Exp. Med.
(1987)- et al.
J. Bacteriol.
(1992) - Hollingshead, S.K., Bessen, D. and Briles, D.E. in Horizontal Gene Transfer: Implications and Consequences (Syvanen, M....
Cited by (63)
Cloning and optimization of induction conditions for mature PsaA (pneumococcal surface adhesin A) expression in Escherichia coli and recombinant protein stability during long-term storage
2011, Protein Expression and PurificationCitation Excerpt :The 10-valent vaccine under technology transfer by Bio-Manguinhos/Fiocruz presents a high-cost process production, and while protecting against main serotypes that cause disease in Brazil, the coverage of Brazilian serotypes by this conjugated vaccine is not complete. As an alternative to the expensive conjugate vaccines, diverse virulence proteins have been investigated in the last two decades as potential vaccine antigen candidates [1–3,5–11] or as carriers for polysaccharides, aiming to enhance coverage for serotypes absent from conjugate vaccines. The most important described proteins are: the pneumococcal toxin pneumolysin [12]; neuraminidases [13], such as NanA and NanB; autolysins [14], such as LytA, LytB and LytC; choline-binding surface proteins family, such as pneumococcal surface protein A (PspA) [15], whose choline-binding repeats are responsible for the attachment of PspA to the surface of the pneumococcus, PspC [16] and choline-binding protein A (CbpA) [17]; a lipoprotein called pneumococcal surface adhesin A (PsaA2) [18–21]; hyaluronate lyase (Hyl), a hyaluronidase that hydrolyses hyaluronan of the extracellular matrix of tissues and possibly contributes to the invasiveness of S. pneumoniae [22]; the putative proteinase maturation protein A (PpmA) [23]; PiuA and PiaA (formerly Pit1A and Pit2A), the lipoprotein components of two S. pneumoniae iron ABC transport systems called Piu (pneumococcal iron uptake) and Pia (pneumococcal iron acquisition) [24]; a family of cell surface-exposed pneumococcal homologous proteins named the pneumococcal histidine triad (Pht), which includes PhtA, PhtB, PhtD and PhtE [25], and S. pneumoniae histidine proteins (PhP), which includes PhpA, PhpB and PhpC [26] and have also been identified as the BVH-3 and BVH-11 families, respectively [27]; and the PavA protein (pneumococcal adherence and virulence factor A), which has been identified as a pneumococcal fibronectin-binding protein [28].
Antibody and T-cell responses during acute and convalescent stages of invasive pneumococcal disease
2011, International Journal of Infectious DiseasesCitation Excerpt :In addition, pneumococcal protein antigens induce T-lymphocyte responses, which contribute to protection against both nasopharyngeal carriage and IPD.14 Some of the protein candidates being considered include pneumolysin, pneumococcal surface protein A (PspA), and choline-binding protein A (CbpA).15–17 However, their role in IPD in humans is not well understood.