The potential for using protein vaccines to protect against otitis media caused by Streptococcus pneumoniae

Briles, David E.; Hollingshead, Susan K.; Nabors, Gary S.; Paton, James C.; Brooks-Walter, Alexis

doi:10.1016/s0264-410x(00)00285-1

Cited by 128 publications

(97 citation statements)

References 30 publications

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“…Most promise is offered by the addition of protein-based vaccines to the current PCV, which may provide protection regardless of serotype (3). Several protein antigens, such as Ply, CbpA, PspA, PsaA, PiaA, PhtB, PhtE (BVH-3), and NanA, have been identified as vaccine candidates (1,6,8,12,14,18,22,23,26,27,29,35). There is evidence that immunization with certain combinations of virulence proteins provides additive or even synergistic protection (5,25).…”

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confidence: 99%

Natural Antibodies against Several Pneumococcal Virulence Proteins in Children during the Pre-Pneumococcal-Vaccine Era: the Generation R Study

et al. 2011

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The currently available pneumococcal vaccines do not protect against all serotypes of Streptococcus pneumoniae. A shift toward nonvaccine serotypes causing colonization and invasive disease has occurred, and studies on protein-based vaccines have been undertaken. We assessed the association between specific antibodies against pneumococcal virulence proteins and colonization and respiratory tract infections (RTIs). Additionally, we assessed the extent to which colonization induces a humoral immune response. Nasopharyngeal swabs collected from children at 1.5, 6, 14, and 24 months of age were cultured for pneumococcus. Serum samples were obtained at birth and at 6, 14, and 24 months (n ‫؍‬ 57 children providing 177 serum samples). Data were collected prior to the pneumococcal vaccine era. IgG, IgA, and IgM levels against 17 pneumococcal protein vaccine candidates were measured using a bead-based flow cytometry technique (xMAP; Luminex Corporation). Information regarding RTIs was questionnaire derived. Levels of IgG against all proteins were high in cord blood, decreased in the first 6 months and increased again thereafter, in contrast to the course of IgA and IgM levels. Specific antibodies were induced upon colonization. Increased levels of IgG against BVH-3, NanA, and SP1003 at 6 months, NanA, PpmA, PsaA, SlrA, SP0189, and SP1003 at 14 months, and SlrA at 24 months were associated with a decreased number of RTIs in the third year of life but not with colonization. Maternal antipneumococcal antibodies did not protect against pneumococcal colonization and infection. Certain antibodies against pneumococcal virulence proteins, some of which are induced by colonization, are associated with a decreased number of RTIs in children. This should be taken into account in future pneumococcal vaccine studies.

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Natural Antibodies against Several Pneumococcal Virulence Proteins in Children during the Pre-Pneumococcal-Vaccine Era: the Generation R Study

et al. 2011

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“…PspA has been most extensively studied for its ability to elicit protective immunity in animal models (5)(6)(7)(8)(9)(10). 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).…”

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confidence: 99%

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

Rohatgi

Dutta²,

Tahir³

et al. 2009

The Journal of Immunology

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Immunization of human volunteers with a single dose of pneumococcal surface protein A (PspA) stimulates broad cross-reactive Abs to heterologous PspA molecules that, when transferred, protect mice from fatal infection with Streptococcus pneumoniae. In this study, we report the molecular characterization of 36 mouse mAbs generated against the extracellular domain of PspA (PspA 3-286 ) from strain R36A. Abs to PspA 3-286 were encoded by diverse V H and V families/genes. The H chain CDR3 and L chain CDR3 lengths were 3-13 (7.8 ؎ 0.5) and 8 -9 (8.7 ؎ 0.2) codons, respectively. Unexpectedly, seven hybridomas expressed H chains that lack D H gene-derived amino acids. Nontemplate-encoded addition(s) were observed in the H chain expressed in six of these seven hybridomas; Palindromic addition(s) were absent. Absence of D H gene-derived amino acids did not prevent antiPspA 3-286 mAbs from attaining average relative avidity. Avidity maturation occurred during primary IgG anti-PspA 3-286 polyclonal Ab response in PspA 3-286 -and R36A-immunized mice. Compared with PspA 3-286 -immunized mice, the relative avidity of the primary polyclonal IgG Abs was higher in R36A immunized mice on days 72, 86, and 100. Two pairs of clonally related hybridomas were observed. D H genes expressed in the majority (75.9%) of the hybridomas used reading frame 3. Analysis of replacement/silent mutation ratio in the CDR and framework regions provided evidence for Ag-driven selection in 11 mAbs. Based on epitope localization experiments, the mAbs were classified into 12 independent groups. ELISA additivity assay indicated that members within a group recognized topographically related epitopes. This study provides molecular insights into the biology of D H -less Abs.

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“…Furthermore, it remains unclear whether serotype replacement will result in significant increases in non-vaccine-type disease in the face of widespread conjugate vaccine use (16). Streptococcus pneumoniae vaccines based on conserved pneumococcal protein antigens such as pneumococcal surface protein A (PspA), pneumolysin, and pneumococcal surface adhesin A (PsaA) are currently under study (4,5) and, if proven effective, may provide an alternative that is less expensive while affording greater coverage.…”

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Age-Specific Immunoglobulin G (IgG) and IgA to Pneumococcal Protein Antigens in a Population in Coastal Kenya

et al. 2004

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Streptococcus pneumoniae is the primary etiological agent of community-acquired pneumonia and a major cause of meningitis and bacteremia. Three conserved pneumococcal proteins-pneumolysin, pneumococcal surface adhesin A (PsaA), and pneumococcal surface protein A (PspA)-are currently being investigated as vaccine candidates. Such protein-based vaccines, if proven effective, could provide a cheaper alternative to conjugate vaccine formulae. Few data from sub-Saharan Africa exist concerning the development of natural antibody to these antigens, however. To investigate the age-specific development of antiprotein immunoglobulin G (IgG) and IgA antibody responses, the sera of 220 persons 2 weeks to 84 years of age from coastal Kenya were assayed using enzyme-linked immunosorbent assays. IgG and IgA antibody responses to each antigen were observed in all age groups. Serum concentrations of IgG and IgA antibody responses to PspA and PdB (a recombinant toxoid derivative of pneumolysin), but not to PsaA, increased significantly with age (P < 0.001). No decline was observed in the sera of the elderly. Anti-protein IgG concentrations were only weakly correlated (0.30 < r < 0.56; P < 0.0001), as were IgA concentrations (0.24 < r < 0.54; P < 0.0001).In Kenya, as in other developing countries, invasive pneumococcal disease (IPD) is responsible for substantial morbidity and mortality (6, 8). In populations for which incidence data are available, the risk of IPD peaks at the end of the first and beginning of the second year of life, declining sharply thereafter. Disease incidence remains low through puberty and early adulthood, rises gradually through middle age, and increases dramatically for individuals over 65 (15,18,23). Recent largescale efficacy trials have shown that a 7-valent pneumococcal conjugate vaccine is effective against IPD and, to a lesser extent, against pneumonia caused by vaccine types (3,12,17). Unfortunately, the price of this vaccine will likely preclude its inclusion in national immunization programs for many countries with the greatest burden of pneumococcal disease. Recent studies also suggest that coverage for such multivalent vaccines may not be universally optimal across the developing world (7, 9). Furthermore, it remains unclear whether serotype replacement will result in significant increases in non-vaccine-type disease in the face of widespread conjugate vaccine use (16). Streptococcus pneumoniae vaccines based on conserved pneumococcal protein antigens such as pneumococcal surface protein A (PspA), pneumolysin, and pneumococcal surface adhesin A (PsaA) are currently under study (4, 5) and, if proven effective, may provide an alternative that is less expensive while affording greater coverage.Immunity to PspA, pneumolysin, and PsaA in European adults and children with and without pneumococcal disease has been studied extensively (20)(21)(22). To the best of our knowledge, the development of naturally acquired immunity to these three antigens in an African population has not yet been described. In...

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The potential for using protein vaccines to protect against otitis media caused by Streptococcus pneumoniae

Cited by 128 publications

References 30 publications

Natural Antibodies against Several Pneumococcal Virulence Proteins in Children during the Pre-Pneumococcal-Vaccine Era: the Generation R Study

Natural Antibodies against Several Pneumococcal Virulence Proteins in Children during the Pre-Pneumococcal-Vaccine Era: the Generation R Study

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

Age-Specific Immunoglobulin G (IgG) and IgA to Pneumococcal Protein Antigens in a Population in Coastal Kenya

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