Publications by authors named "Merit Melin"

16 Publications

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Serological and molecular findings during SARS-CoV-2 infection: the first case study in Finland, January to February 2020.

Euro Surveill 2020 03;25(11)

Department of Health Security, Finnish Institute for Health and Welfare (THL), Helsinki, Finland.

The first case of coronavirus disease (COVID-19) in Finland was confirmed on 29 January 2020. No secondary cases were detected. We describe the clinical picture and laboratory findings 3-23 days since the first symptoms. The SARS-CoV-2/Finland/1/2020 virus strain was isolated, the genome showing a single nucleotide substitution to the reference strain from Wuhan. Neutralising antibody response appeared within 9 days along with specific IgM and IgG response, targeting particularly nucleocapsid and spike proteins.
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http://dx.doi.org/10.2807/1560-7917.ES.2020.25.11.2000266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096774PMC
March 2020

Assessment of an Antibody-in-Lymphocyte Supernatant Assay for the Etiological Diagnosis of Pneumococcal Pneumonia in Children.

Front Cell Infect Microbiol 2019 17;9:459. Epub 2020 Jan 17.

Patan Academy of Health Sciences, Kathmandu, Nepal.

New diagnostic tests for the etiology of childhood pneumonia are needed. We evaluated the antibody-in-lymphocyte supernatant (ALS) assay to detect immunoglobulin (Ig) G secretion from peripheral blood mononuclear cell (PBMC) culture, as a potential diagnostic test for pneumococcal pneumonia. We enrolled 348 children with pneumonia admitted to Patan Hospital, Kathmandu, Nepal between December 2015 and September 2016. PBMCs sampled from participants were incubated for 48 h before harvesting of cell culture supernatant (ALS). We used a fluorescence-based multiplexed immunoassay to measure the concentration of IgG in ALS against five conserved pneumococcal protein antigens. Of children with pneumonia, 68 had a confirmed etiological diagnosis: 12 children had pneumococcal pneumonia (defined as blood or pleural fluid culture-confirmed; or plasma CRP concentration ≥60 mg/l and nasopharyngeal carriage of serotype 1 pneumococci), and 56 children had non-pneumococcal pneumonia. Children with non-pneumococcal pneumonia had either a bacterial pathogen isolated from blood (six children); or C-reactive protein <60 mg/l, absence of radiographic consolidation and detection of a pathogenic virus by multiplex PCR (respiratory syncytial virus, influenza viruses, or parainfluenza viruses; 23 children). Concentrations of ALS IgG to all five pneumococcal proteins were significantly higher in children with pneumococcal pneumonia than in children with non-pneumococcal pneumonia. The concentration of IgG in ALS to the best-performing antigen discriminated between children with pneumococcal and non-pneumococcal pneumonia with a sensitivity of 1.0 (95% CI 0.73-1.0), specificity of 0.66 (95% CI 0.52-0.78) and area under the receiver-operating characteristic curve (AUROCC) 0.85 (95% CI 0.75-0.94). Children with pneumococcal pneumonia were older than children with non-pneumococcal pneumonia (median 5.6 and 2.0 years, respectively, < 0.001). When the analysis was limited to children ≥2 years of age, assay of IgG ALS to pneumococcal proteins was unable to discriminate between children with pneumococcal pneumonia and non-pneumococcal pneumonia (AUROCC 0.67, 95% CI 0.47-0.88). This method detected spontaneous secretion of IgG to pneumococcal protein antigens from cultured PBMCs. However, when stratified by age group, assay of IgG in ALS to pneumococcal proteins showed limited utility as a test to discriminate between pneumococcal and non-pneumococcal pneumonia in children.
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http://dx.doi.org/10.3389/fcimb.2019.00459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988833PMC
September 2020

Multilaboratory Comparison of Pneumococcal Multiplex Immunoassays Used in Immunosurveillance of Streptococcus pneumoniae across Europe.

mSphere 2019 11 27;4(6). Epub 2019 Nov 27.

National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands.

Surveillance studies are required to estimate the impact of pneumococcal vaccination in both children and the elderly across Europe. The World Health Organization (WHO) recommends use of enzyme immunoassays (EIAs) as standard methods for immune surveillance of pneumococcal antibodies. However, as levels of antibodies to multiple serotypes are monitored in thousands of samples, a need for a less laborious and more flexible method has evolved. Fluorescent-bead-based multiplex immunoassays (MIAs) are suitable for this purpose. An increasing number of public health and diagnostic laboratories use MIAs, although the method is not standardized and no international quality assessment scheme exists. The EU Pneumo Multiplex Assay Consortium was initiated in 2013 to advance harmonization of MIAs and to create an international quality assessment scheme. In a multilaboratory comparison organized by the consortium, agreement among nine laboratories that used their own optimized MIA was assessed on a panel of 15 reference sera for 13 pneumococcal serotypes with the new WHO standard 007sp. Agreement was assessed in terms of assay accuracy, reproducibility, repeatability, precision, and bias. The results indicate that the evaluated MIAs are robust and reproducible for measurement of vaccine-induced antibody responses. However, some serotype-specific variability in the results was observed in comparisons of polysaccharides from different sources and of different conjugation methods, especially for serotype 4. On the basis of the results, the consortium has contributed to the harmonization of MIA protocols to improve reliability of immune surveillance of Serology of is challenging due to existence of multiple clinically relevant serotypes and the introduction of multivalent vaccines in national immunization programs. Multiplex immunoassays (MIAs) are applied as high-throughput cost-effective methods for serosurveillance, and yet laboratories use their own protocols. The aims of this study were to assess the agreement of results generated by MIAs in different laboratories within the EU Pneumo Multiplex Assay Consortium, to analyze factors contributing to differences in outcome, and to create a harmonized protocol. The study demonstrated good agreement of results of MIAs performed by laboratories using controlled assays for determination of levels of vaccine-induced pneumococcal antibodies. The EU Pneumo Multiplex Assay Consortium is open to everyone working in public health services, and it aims to facilitate efforts by participants to run and maintain a cost-effective, reproducible, high-quality MIA platform.
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http://dx.doi.org/10.1128/mSphere.00455-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881716PMC
November 2019

Comparison of serological assays using pneumococcal proteins or polysaccharides for detection of Streptococcus pneumoniae infection in children with community-acquired pneumonia.

J Immunol Methods 2018 09 20;460:72-78. Epub 2018 Jun 20.

Postgraduate Program in Health Sciences, Federal University of Bahia School of Medicine, Salvador, Brazil; Department of Paediatrics, Federal University of Bahia School of Medicine, Salvador, Brazil.

The aim of this study was to compare the results of serological assays using pneumococcal proteins or polysaccharides for the detection of pneumococcal infection in childhood pneumonia. Serological assays measured IgG against eight pneumococcal proteins (Ply,CbpA,PspA1,PspA2,PcpA,PhtD,StkP-C,PcsB-N), C-polysaccharide [in the whole study population, n = 183], or 19 pneumococcal capsular polysaccharides (1,2,4,5,6B,7F,8,9 V,10A,11A,12F,14,15B,17F,18C,19F,20,23F,33F) [only in a subgroup of patients, n = 53] in paired serum samples of children aged <5 years-old hospitalized with clinical and radiological diagnosis of community-acquired pneumonia. We also performed an inhibition of binding test with the anti-capsular polysaccharide assay in order to confirm the specificity of the antibody responses detected. Invasive pneumococcal pneumonia was investigated by blood culture and PCR (ply-primer). Among 183 children, the anti-protein assay detected antibody response in 77/183(42.1%) patients and the anti-C-polysaccharide assay in 28/183(15.3%) patients. In a subgroup of 53 children, the anti-protein assay detected response in 32/53(60.4%) patients, the anti-C-polysaccharide assay in 11/53(20.8%) patients, and the anti-capsular polysaccharide in 25/53(47.2%) patients. Simultaneous antibody responses against ≥2 different capsular polysaccharides were detected in 11/53(20.8%) patients and this finding could not be explained by cross-reactivity between different serotypes. Among 13 patients with invasive pneumococcal pneumonia, the sensitivity of the anti-protein assay was 92.3%(12/13), of the anti-C-polysaccharide assay 30.8%(4/13), and of the anti-capsular polysaccharide assay 46.2%(6/13). The serological assay using pneumococcal proteins is more sensitive for the detection of pneumococcal infection in children with pneumonia than the assay using pneumococcal polysaccharides. Future studies on childhood pneumonia aetiology should consider applying serological assays using pneumococcal proteins.
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http://dx.doi.org/10.1016/j.jim.2018.06.011DOI Listing
September 2018

Similar Antibody Levels in 3-Year-Old Children Vaccinated Against Measles, Mumps, and Rubella at the Age of 12 Months or 18 Months.

J Infect Dis 2016 06 9;213(12):2005-13. Epub 2016 Feb 9.

Department of Health Protection, National Institute for Health and Welfare.

Background: Measles-mumps-rubella (MMR) vaccinations have been offered to Finnish children at 14-18 months and 6 years of age. In May 2011, the recommended age for the first vaccine dose was lowered to 12 months because of the European measles epidemic.

Methods: Fingertip capillary blood samples were collected from 3-year-old Finnish children vaccinated once with MMR vaccine at 11-19 months of age. The immunoglobulin G (IgG) antibodies to all 3 MMR antigens were measured with enzyme-linked immunosorbent assay. Neutralizing antibodies and the avidity of antibodies were measured for measles virus.

Results: From April through October 2013, 187 children were enrolled. Equally high proportions of the samples were seropositive for measles virus, mumps virus, or rubella virus antibodies, and there were no significant differences in the IgG antibody concentrations in children vaccinated at 11-13 months of age, compared with those vaccinated at 17-19 months of age. However, among children vaccinated at 11-13 months of age, boys had lower antibody concentrations than girls. Neutralizing measles virus antibody titers were above the threshold for protective immunity in all 78 samples analyzed. The measles virus antibody avidity indexes were high for all children.

Conclusions: MMR induces similar antibody responses in 12-month-old children as compared to 18-month-old children, but in boys increasing age appears to improve the antibody responses.
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http://dx.doi.org/10.1093/infdis/jiw058DOI Listing
June 2016

Predisposition to Childhood Otitis Media and Genetic Polymorphisms within the Toll-Like Receptor 4 (TLR4) Locus.

PLoS One 2015 15;10(7):e0132551. Epub 2015 Jul 15.

Department of Otorhinolaryngology, Helsinki University Central Hospital, Helsinki, Finland.

Background: Predisposition to childhood otitis media (OM) has a strong genetic component, with polymorphisms in innate immunity genes suspected to contribute to risk. Studies on several genes have been conducted, but most associations have failed to replicate in independent cohorts.

Methods: We investigated 53 gene polymorphisms in a Finnish cohort of 624 cases and 778 controls. A positive association signal was followed up in a tagging approach and tested in an independent Finnish cohort of 205 cases, in a British cohort of 1269 trios, as well as in two cohorts from the United States (US); one with 403 families and the other with 100 cases and 104 controls.

Results: In the initial Finnish cohort, the SNP rs5030717 in the TLR4 gene region showed significant association (OR 1.33, P = .003) to OM. Tagging SNP analysis of the gene found rs1329060 (OR 1.33, P = .002) and rs1329057 (OR 1.29, P = .003) also to be associated. In the more severe phenotype the association was stronger. This finding was supported by an independent Finnish case cohort, but the associations failed to replicate in the British and US cohorts. In studies on TLR4 signaling in 20 study subjects, the three-marker risk haplotype correlated with a decreased TNFα secretion in myeloid dendritic cells.

Conclusions: The TLR4 gene locus, regulating the innate immune response, influences the genetic predisposition to childhood OM in a subpopulation of patients. Environmental factors likely modulate the genetic components contributing to the risk of OM.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132551PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4503307PMC
May 2016

Infections in infants fed formula supplemented with bovine milk fat globule membranes.

J Pediatr Gastroenterol Nutr 2015 Mar;60(3):384-9

*Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden †Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland ‡Department of Nutrition, University of California, Davis.

Objectives: Observational studies have shown that even in high-income countries formula-fed infants have a higher incidence of acute otitis media (AOM), and gastrointestinal and respiratory tract infections during the first year of life compared with breast-fed infants. We hypothesized that components of the milk fat globule membrane (MFGM) may be responsible for some of these differences and that supplementation with bovine MFGM would decrease the infectious morbidity in formula-fed infants.

Methods: In a double-blind randomized controlled trial, 160 formula-fed infants received experimental formula (EF) supplemented with bovine MFGM (EF) or unsupplemented standard formula (SF) from <2 months until 6 months of age. A breast-fed reference group consisted of 80 infants. Disease symptoms, health care contacts, and medication were recorded by the parents until 12 months of age. Serum immunoglobulin G for 10 pneumococcal serotypes was analyzed at 6 months of age.

Results: The cumulative incidence of AOM during the intervention was lower in the EF group than in the SF group (1% vs 9%, P = 0.034), and did not differ from the breast-fed reference group (0%, P = 1.0). The incidence (25% vs 43%, P = 0.021) and longitudinal prevalence (P = 0.012) of antipyretic use were significantly lower in the EF group than in the SF group. Serum immunoglobulin G concentrations against pneumococcal serotypes 1, 5, and 14 were lower in the EF group than in the SF group.

Conclusions: Supplementation of formula with bovine MFGM reduces the risk of AOM, decreases antipyretics use in formula-fed infants, and has immunomodulatory effects on humoral response against pneumococcus vaccine.
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http://dx.doi.org/10.1097/MPG.0000000000000624DOI Listing
March 2015

Role of Pht proteins in attachment of Streptococcus pneumoniae to respiratory epithelial cells.

Infect Immun 2014 Apr 3;82(4):1683-91. Epub 2014 Feb 3.

Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland.

Pneumococcal adherence to mucosal surfaces is a critical step in nasopharyngeal colonization, but so far few pneumococcal adhesins involved in the interaction with host cells have been identified. PhtA, PhtB, PhtD, and PhtE are conserved pneumococcal surface proteins that have proven promising as vaccine candidates. One suggested virulence function of Pht proteins is to mediate adherence at the respiratory mucosa. In this study, we assessed the role of Pht proteins in pneumococcal binding to respiratory epithelial cells. Pneumococci were incubated with human nasopharyngeal epithelial cells (Detroit-562) and lung epithelial cells (A549 and NCI-H292), and the proportion of bound bacteria was measured by plating viable counts. Strains R36A (unencapsulated), D39 (serotype 2), 43 (serotype 3), 4-CDC (serotype 4), and 2737 (serotype 19F) with one or more of the four homologous Pht proteins deleted were compared with their wild-type counterparts. Also, the effect of anti-PhtD antibodies on the adherence of strain 2737 to the respiratory epithelial cells was studied. Our results suggest that Pht proteins play a role in pneumococcal adhesion to the respiratory epithelium. We also found that antibody to PhtD is able to inhibit bacterial attachment to the cells, suggesting that antibodies against PhtD present at mucosal surfaces might protect from pneumococcal attachment and subsequent colonization. However, the relative significance of Pht proteins to the ability of pneumococci to bind in vitro to epithelial cells depends on the genetic background and the capsular serotype of the strain.
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http://dx.doi.org/10.1128/IAI.00699-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3993382PMC
April 2014

Development of cross-reactive antibodies to the proline-rich region of pneumococcal surface protein A in children.

Vaccine 2012 Nov 13;30(50):7157-60. Epub 2012 Oct 13.

Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland.

Pneumococcal surface protein A (PspA) is an important virulence factor of Streptococcus pneumoniae and a candidate for inclusion in future protein-based vaccines. The surface-exposed α-helical region of PspA is immunogenic and frequently cross-reactive, but also variable in structure. Sequence and serological differences in this region divide PspAs into two major families. We showed previously that children preferentially develop antibodies limited to the PspA family of the colonizing strain. In this study, sera of children with history of pneumococcal colonization were analyzed for presence of IgG antibodies to the conserved proline-rich region (PRR) of PspA. The results indicate that children produce antibodies to the PRR upon exposure to pneumococci. The PRR-specific antibodies were elicited regardless of the PspA family of the infecting strain. The results indicate that the PRR antigen elicits broadly cross-reactive antibodies that may have the potential to provide cross-protection against a broad spectrum of pneumococcal strains.
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http://dx.doi.org/10.1016/j.vaccine.2012.10.004DOI Listing
November 2012

Serotype-related variation in susceptibility to complement deposition and opsonophagocytosis among clinical isolates of Streptococcus pneumoniae.

Infect Immun 2010 Dec 20;78(12):5252-61. Epub 2010 Sep 20.

National Institute for Health and Welfare, Department of Vaccination and Immune Protection, Helsinki, Finland.

The polysaccharide capsule is a major virulence factor of Streptococcus pneumoniae; it affects complement resistance and shields the bacterium from phagocytes. Certain capsular serotypes appear to be better able to cause invasive disease than others. Serotypes 1 and 5 are common causes of invasive disease but are rarely isolated from healthy carriers, whereas serotypes 6B and 23F are more frequently isolated from carriage than invasive disease. We have recently shown that serotypes 6B and 19F differ in resistance to complement C3 deposition and opsonophagocytic killing. In this study we assessed the complement resistance and susceptibility to opsonophagocytosis of several other serotypes targeted by the pneumococcal conjugate vaccines. Clinical isolates of serotypes 1, 4, 5, 14, 18C, and 23F were tested along reference strains of corresponding capsular types. The concentration of anticapsular antibodies required for opsonophagocytic killing correlated inversely with C3 deposition on the serotype. Serotype 1 was the most resistant of the clinical isolates to C3 deposition and, along with serotypes 5 and 19F, required the highest concentration of capsule antibodies for opsonophagocytic killing, whereas serotype 23F was the most sensitive to opsonophagocytosis. Sensitivity to C3 deposition and opsonophagocytosis was associated with serotype-specific mortality of invasive pneumococcal disease, suggesting that the primary pathogens, such as serotypes 1 and 5, are more resistant to complement and require a higher concentration of capsule antibodies for opsonophagocytic killing than the opportunistic serotypes such as 6B and 23F, which are associated with a more severe disease outcome.
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http://dx.doi.org/10.1128/IAI.00739-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981318PMC
December 2010

The capsular serotype of Streptococcus pneumoniae is more important than the genetic background for resistance to complement.

Infect Immun 2010 Dec 20;78(12):5262-70. Epub 2010 Sep 20.

National Institute for Health and Welfare, Department of Vaccination and Immune Protection, Helsinki, Finland.

The polysaccharide capsule of Streptococcus pneumoniae inhibits phagocytic killing by innate immune mechanisms. Certain serotypes are associated with invasive disease while others with a nasopharyngeal carriage. The invasiveness of serotypes may partly be explained by ability to resist deposition of complement (C3) on the bacterial surface and consequent opsonophagocytic killing. In our previous studies, we observed that clinical isolates of serotypes 1 and 5, which are rarely detected in asymptomatic carriage, were resistant to complement deposition and opsonophagocytosis, whereas serotypes 6B and 23F, both common in carriage, were more sensitive to deposition of C3 and opsonophagocytic killing. However, presence of significant variation in C3 deposition between isolates of the same serotype indicated that factors other than the capsule also affect complement resistance. To distinguish the relative effect of the capsular serotype and other virulence factors on C3 deposition, we compared capsule-switched mutants prepared in genetic backgrounds of pneumococcal strains TIGR4, 603, and 618. Clinical isolates which had the same multilocus sequence type but expressed different serotypes were also compared. We found that the serotype had a significant impact on complement resistance and that the more resistant the strain was to complement, the higher was the concentration of polysaccharide-specific antibodies required for opsonophagocytic killing. Comparison of strains expressing the same capsular polysaccharides in the different genetic backgrounds and various capsular mutants of the same strain suggests that while the genotype affects complement resistance, the serotype is the most important determinant. Differences between serotypes were more significant than the differences between strains.
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http://dx.doi.org/10.1128/IAI.00740-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981297PMC
December 2010

Interaction of pneumococcal histidine triad proteins with human complement.

Infect Immun 2010 May 1;78(5):2089-98. Epub 2010 Mar 1.

National Institute for Health and Welfare, Department of Vaccination and Immune Protection, Mannerheimintie 166, 00300 Helsinki, Finland.

The pneumococcal histidine triad (Pht) proteins PhtA, PhtB, PhtD, and PhtE form a group of conserved pneumococcal surface proteins. Humans produce antibodies to Pht proteins upon exposure to pneumococcus, and immunization of mice has provided protective immunity against sepsis and pneumonia and reduced nasopharyngeal colonization. Pht proteins are candidates for inclusion in multicomponent pneumococcal protein vaccines. Their biological function in pneumococcal infections is not clear, but a role in complement inhibition has been suggested. We measured complement deposition on wild-type and Pht mutant strains in four genetic backgrounds: Streptococcus pneumoniae D39 (serotype 2) and R36A (unencapsulated derivative of D39) and strains of serotypes 3, 4, and 19F. PspA and PspC single and double mutants were compared to the wild-type and Pht-deficient D39 strains. Factor H binding was measured to bacterial cells, lysates, and protein antigens. Deletion of all four Pht proteins (Pht(-)) resulted in increased C3 deposition on the serotype 4 strain but not on the other strains. Pht antigens did not bind factor H, and deletion of Pht proteins did not affect factor H binding by bacterial lysates. The Pht(-) mutant serotype 4 strain bound slightly less factor H than the wild-type strain when binding was measured by flow cytometry. Pht proteins may play a role in immune evasion, but the mechanism of function is unlikely to be mediated by factor H binding. The relative contribution of Pht proteins to the inhibition of complement deposition is likely to be affected by the presence of other pneumococcal proteins and to depend on the genetic background.
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http://dx.doi.org/10.1128/IAI.00811-09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2863542PMC
May 2010

Streptococcus pneumoniae capsular serotype 19F is more resistant to C3 deposition and less sensitive to opsonophagocytosis than serotype 6B.

Infect Immun 2009 Feb 1;77(2):676-84. Epub 2008 Dec 1.

National Public Health Institute, Department of Vaccines, Helsinki, Finland.

The polysaccharide capsule is a major virulence mechanism of Streptococcus pneumoniae, shielding the bacterium from phagocytes. Capsule types may differ in their abilities to resist immune defense. Antibody-mediated complement activation and opsonophagocytosis are crucial in protection against pneumococcus. Conjugate vaccine trials suggest imperfect protection against 19F. We have previously shown that significantly more anti-19F than anti-6B antibody is needed for killing in the opsonophagocytic assay (OPA). In this study, we explored whether the amount of C3 deposited on serotype 6B and 19F pneumococcal strains reflects their sensitivity to opsonophagocytosis. We compared clinical 6B and 19F nasopharyngeal, middle ear, and blood isolates as well as reference OPA strains (n = 16) for their sensitivity to opsonophagocytosis and C3 deposition. Sixfold anticapsular antibody concentrations were required for 50% opsonophagocytic killing of 19F compared to that of 6B strains. Serotype 19F was more resistant to C3 deposition than 6B. Complement deposition and opsonophagocytosis were dependent on the concentration of anticapsular antibodies. Differences between pneumococcal serotypes in antibody-mediated protection may partly be explained by the abilities of the capsules to resist complement deposition. These findings support previous studies suggesting that higher antibody concentrations to the capsular polysaccharide are needed for protection against disease caused by serotype 19F than that caused by 6B.
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http://dx.doi.org/10.1128/IAI.01186-08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2632042PMC
February 2009

Development of antibodies to PspA families 1 and 2 in children after exposure to Streptococcus pneumoniae.

Clin Vaccine Immunol 2008 Oct 27;15(10):1529-35. Epub 2008 Aug 27.

National Public Health Institute (KTL), Department of Vaccines, Mannerheimintie 166, 00300 Helsinki, Finland.

Pneumococcal surface protein A (PspA) is an important virulence factor of Streptococcus pneumoniae. PspA exists as two major families, which include variable but serologically cross-reactive proteins. Previous studies with a family 1 PspA antigen suggested that children develop low concentrations of anti-PspA after pneumococcal carriage or infection. In this study, antibody to PspA families 1 and 2 was measured by an enzyme immunoassay of the serum and saliva of children with a history of culture-proven pneumococcal colonization and/or acute otitis media and in the serum and saliva of adults. The PspA families of the pneumococcal strains isolated from children were determined. The majority of the children had high serum and salivary anti-PspA concentrations to the PspA family they had encountered and low concentrations to the other, whereas adults had high antibody concentrations to both PspA families, both in serum and in saliva. The results suggest that children have a relatively family-specific antibody response to the PspA family they have been exposed to and that any PspA vaccine for children should contain members of both major PspA families.
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http://dx.doi.org/10.1128/CVI.00181-08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2565922PMC
October 2008

Distribution of pneumococcal surface protein A families 1 and 2 among Streptococcus pneumoniae isolates from children in finland who had acute otitis media or were nasopharyngeal carriers.

Clin Vaccine Immunol 2008 Oct 27;15(10):1555-63. Epub 2008 Aug 27.

National Public Health Institute (KTL), Department of Vaccines, Mannerheimintie 166, 00300 Helsinki, Finland.

PspA is a structurally variable surface protein important to the virulence of pneumococci. PspAs are serologically cross-reactive and exist as two major families. In this study, we determined the distribution of PspA families 1 and 2 among pneumococcal strains isolated from the middle ear fluid (MEF) of children with acute otitis media and from nasopharyngeal specimens of children with pneumococcal carriage. We characterized the association between the two PspA families, capsular serotypes, and multilocus sequence types (STs) of the pneumococcal isolates. MEF isolates (n = 201) of 109 patients and nasopharyngeal isolates (n = 173) of 49 children were PspA family typed by whole-cell enzyme immunoassay (EIA). Genetic typing (PCR) of PspA family was done for 60 isolates to confirm EIA typing results. The prevalences of PspA families 1 and 2 were similar among pneumococci isolated from MEF (51% and 45%, respectively) and nasopharyngeal specimens (48% each). Isolates of certain capsule types as well as isolates of certain STs showed statistical associations with either family 1 or family 2 PspA. Pneumococci from seven children with multiple pneumococcal isolates appeared to express serologically different PspA families in different isolates of the same serotype; in three of the children the STs of the isolates were the same, suggesting that antigenic changes in the PspA expressed may have taken place. The majority of the isolates (97%) belonged to either PspA family 1 or family 2, suggesting that a combination including the two main PspA families would make a good vaccine candidate.
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http://dx.doi.org/10.1128/CVI.00177-08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2565924PMC
October 2008

Antibodies to pneumococcal surface protein A families 1 and 2 in serum and saliva of children and the risk of pneumococcal acute otitis media.

J Infect Dis 2007 Nov 31;196(10):1528-36. Epub 2007 Oct 31.

Department of Vaccines, National Public Health Institute, Mannerheimintie 166, Helsinki, Finland.

Background: Pneumococcal surface protein A (PspA) is a highly variable yet cross-reactive protein that exists as 2 major families. We assessed the development of human serum and salivary antibodies against the PspA families 1 (PspA1) and 2 (PspA2) in early childhood and their role in the prevention of pneumococcal acute otitis media (AOM).

Methods: Serum levels of IgG and salivary levels of IgA antibodies to PspA1 and PspA2 were measured by use of enzyme immunoassay from the samples from the Finnish Otitis Media Cohort Study obtained at the ages of 12 months (287 and 160 samples, respectively) and 18 months (258 and 131 samples, respectively). The Cox proportional hazard model was used to evaluate the relative risk (RR) of pneumococcal AOM during the 6 months after sampling relative to concentration of serum or presence of salivary anti-PspA in the samples.

Results: Anti-PspA1 and anti-PspA2 concentrations at 12 and 18 months were related to prior culture-confirmed pneumococcal exposure. The concentrations of serum anti-PspA were not significantly associated with the risk of pneumococcal AOM. At 18 months, the presence of salivary anti-PspA was significantly associated with a lower risk of pneumococcal AOM during the 6 months after sampling (RR, 0.27 [95% confidence interval, 0.11-0.69]).

Conclusions: The lowered risk of pneumococcal AOM associated with the presence of salivary anti-PspA at 18 months suggests that mucosal anti-PspA antibodies have a role in the prevention of pneumococcal AOM.
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http://dx.doi.org/10.1086/522607DOI Listing
November 2007