Human antibodies to pneumococcal surface protein A in health and disease

Virolainen, Anni; Russell, William O.; Crain, Marilyn J.; Rapola, Satu; Käyhty, Helena; Briles, David E.

doi:10.1097/00006454-200002000-00011

Cited by 51 publications

(29 citation statements)

References 13 publications

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“…Recent studies of humans have shown that antibodies to pneumolysin, PspA, and PsaA are present in serum in healthy people and patients with invasive disease (43,48). IgA antibodies are also found in saliva in children, and patients with positive cultures from nasopharyngeal swabs or from middle ear fluid had higher antigen-specific IgA concentrations than culture-negative controls (46).…”

Section: Discussionmentioning

confidence: 99%

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Immune Responses to Novel Pneumococcal Proteins Pneumolysin, PspA, PsaA, and CbpA in Adenoidal B Cells from Children

2002

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Studies of mice suggest that pneumococcal proteins, including PspA, pneumolysin, PsaA, and CbpA, are promising vaccine candidates. To determine whether these proteins are good mucosal immunogens in humans, adenoidal lymphocytes from 20 children who had adenoidectomies were isolated and tested by ELISpot for antigen-specific antibody-secreting cells (ASCs). Cells were also cultured for 7 days in the presence of a concentrated culture supernatant (CCS) from a type 14 strain of pneumococcus which contained secreted pneumococcal proteins, including PspA, pneumolysin, PsaA, and CbpA, and then tested by ELISpot. ELISpot assays done on freshly isolated cells detected ASCs to all four antigens in most children studied. However, there were differences both between antigens and between isotypes. The densities of immunoglobulin G (IgG) ASCs against both PsaA and CbpA were significantly higher than those of ASCs for PspA and PdB (pneumolysin toxoid B) (P < 0.001). For all antigens, the numbers of IgA ASCs tended to be lower than those

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Section: Discussionmentioning

confidence: 99%

“…Preliminary studies of mice have shown that immunization with these proteins can protect against infection with multiple serotypes of pneumococcus (1) and/or prevent nasopharyngeal carriage (9,10). It has been shown that pneumococcal carriage and infections induce salivary and serum antibodies to PsaA, pneumolysin, and PspA in children (43,46,48).…”

mentioning

confidence: 99%

Immune Responses to Novel Pneumococcal Proteins Pneumolysin, PspA, PsaA, and CbpA in Adenoidal B Cells from Children

2002

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“…Antibodies to PspA were measured using standard enzyme-linked immunosorbent assay (ELISA) methods (39,47). We used stored plasma samples instead of serum samples.…”

Section: Subjectsmentioning

confidence: 99%

Impaired Function of Antibodies to Pneumococcal Surface Protein A but Not to Capsular Polysaccharide in Mexican American Adults with Type 2 Diabetes Mellitus

Mathews¹,

Brown

Martinez³

et al. 2012

Clin Vaccine Immunol

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ABSTRACTThe goal of the study was to determine baseline protective titers of antibodies toStreptococcus pneumoniaesurface protein A (PspA) and capsular polysaccharide in individuals with and individuals without type 2 diabetes mellitus. A total of 561 individuals (131 individuals with diabetes and 491 without) were screened for antibodies to PspA using a standard enzyme-linked immunosorbent assay (ELISA). A subset of participants with antibodies to PspA were retested using a WHO ELISA to determine titers of antibodies to capsular polysaccharide (CPS) (serotypes 4, 6B, 9V, 14, 18C, 19A, 19F, and 23F). Functional activity of antibodies was measured by assessing their ability to enhance complement (C3) deposition on pneumococci and promote killing of opsonized pneumococci. Titers of antibodies to protein antigens (PspA) were significantly lower in individuals with diabetes than controls without diabetes (P= 0.01), and antibodies showed a significantly reduced complement deposition ability (P= 0.02). Both antibody titers and complement deposition were negatively associated with hyperglycemia. Conversely, titers of antibodies to capsular polysaccharides were either comparable between the two groups or were significantly higher in individuals with diabetes, as was observed for CPS 14 (P= 0.05). The plasma specimens from individuals with diabetes also demonstrated a higher opsonophagocytic index against CPS serotype 14. Although we demonstrate comparable protective titers of antibodies to CPS in individuals with and individuals without diabetes, those with diabetes had lower PspA titers and poor opsonic activity strongly associated with hyperglycemia. These results suggest a link between diabetes and impairment of antibody response.

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“…Antibodies to PsaA, PspA and Ply have been found in human serum and mucosal secretions [12,13], emerging with age and exposure to pneumococci. Children with invasive pneumococcal infection had lower acute phase serum anti-PspA titers than controls in one study, implying a protective role for these antibodies [14]. To explore these pneumococcal protein antigens further as human vaccines, it is important to characterize naturally acquired immune responses particularly in relation to nasopharyngeal carriage of pneumococci and to investigate whether they are protective.…”

Section: Introductionmentioning

confidence: 99%

Serum and mucosal antibody responses to pneumococcal protein antigens in children:relationships with carriage status

et al. 2005

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Streptococcus pneumoniae causes significant morbidity and mortality especially in children. Some pneumococcal protein antigens can protect mice against infection. Little information is available concerning the nature of naturally acquired protective immunity to pneumococci in humans induced by these antigens. This study investigates the relationships between systemic and local antibody production and carriage in children. Children undergoing adenoidectomy (n=112, ages 2-12 years) were studied. Nasopharyngeal swabs were collected for pneumococcal culture. Serum and saliva were assayed for antibodies to several pneumococcal proteins: choline binding protein A (CbpA), pneumolysin (Ply), pneumococcal surface adhesin A (PsaA) and pneumococcal surface protein A (PspA). Adenoidal mononuclear cells (MNC) were cultured with pneumococcal culture supernatants or recombinant proteins. Cell culture supernatants were analyzed for antigen-specific antibodies. Carriage rates fell with age and serum levels of anti-CbpA, Ply and PspA rose. Anti-CbpA and -Ply serum and salivary IgG antibody levels were higher in children who were culture negative than those who were colonized. Antigen stimulation increased respective antigen-specific IgG production by adenoidal MNC and these responses were greater in those who were colonized than in culture-negative children. Antibodies to CbpA and Ply may protect children aged 2 years and older against pneumococcal colonization. Adenoids may be important local induction and effector sites for both mucosal and systemic antibody production to pneumococcal proteins in children.

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Human antibodies to pneumococcal surface protein A in health and disease

Abstract: We demonstrate for the first time the existence of antibodies to PspA in human sera in health and disease. The findings in ill children suggest that antibodies to PspA might play a role in protection against pneumococcal disease.

Cited by 51 publications

References 13 publications

Immune Responses to Novel Pneumococcal Proteins Pneumolysin, PspA, PsaA, and CbpA in Adenoidal B Cells from Children

Immune Responses to Novel Pneumococcal Proteins Pneumolysin, PspA, PsaA, and CbpA in Adenoidal B Cells from Children

Impaired Function of Antibodies to Pneumococcal Surface Protein A but Not to Capsular Polysaccharide in Mexican American Adults with Type 2 Diabetes Mellitus

Serum and mucosal antibody responses to pneumococcal protein antigens in children:relationships with carriage status

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