Biomedical subjects

Jacquelyn S Sampson

Publications and source records attributed to Jacquelyn S Sampson.

7 recordsLinked to original sources

PubMed2006

CCL5 modulates pneumococcal immunity and carriage.

Understanding the requirements for protection against pneumococcal carriage and pneumonia will greatly benefit efforts in controlling these diseases. Recently, it has been shown that genetic polymorphisms can result in diminished expression of CCL5, which results in increased susceptibility to and progression of infectious diseases. We show that CCL5, together with Th cytokine mRNA expression, is temporally up-regulated during pneumococcal carriage. To determine the contribution of CCL5 to pneumococcal surface antigen A-specific humoral and cellular pneumococcal immunity, mice were treated with anti-CCL5 or control Abs before and during Streptococcus pneumoniae strain EF3030-challenge for the initiation of carriage. CCL5 blockade resulted in a decrease of CD4(+) and CD8(+) T cells as well as CD11b(+) cells in the spleen, cervical lymph node, lung, and nasopharyngeal associated lymphoid tissue during the recognition phase of the pneumococcal adaptive immune response. CCL5 blockade significantly reduced the Ag-specific IgG2a and IgG1 Abs in serum and IgA Ab levels in nasal washes. These decreases also corresponded to reductions in Ag-specific T cell (mucosal and systemic) responses. CCL5 inhibition resulted in decreasing the quantity of IL-4- and IFN-gamma-secreting CD4(+) T cells and increasing the number of Ag-specific IL-10-producing CD4(+) T cells; these changes combined also corresponded with the transition from pneumococcal carriage to lethal pneumonia. These data suggest that CCL5 is an essential factor for the induction and maintenance of protective pneumococcal immunity.

Animals↗

PubMed2005

Diagnosis of invasive pneumococcal disease among children in Kenya with enzyme-linked immunosorbent assay for immunoglobulin G antibodies to pneumococcal surface adhesin A.

Diagnostic techniques for invasive pneumococcal disease (IPD) in children are insensitive and underestimate both the burden of disease and the cost-effectiveness of pneumococcal conjugate vaccination (PCV). Consequently, there is little demand for the highly effective PCV outside the United States and Europe. In Kenya, diagnosis of pneumococcal pneumonia in adults was achieved with a sensitivity of 0.70 and a specificity of 0.98 using enzyme-linked immunosorbent assays (ELISAs) of paired plasma samples for immunoglobulin G (IgG) to pneumococcal surface adhesin A (PsaA). We aimed to validate the same technique in children. We assayed paired blood samples from 98 children with IPD, 95 age-matched children with malaria/anemia, and 97 age-matched healthy controls by using an ELISA for anti-PsaA IgG. Sensitivity and specificity were determined in IPD patients and healthy controls. Specificity (0.97; 95% confidence interval [CI], 0.91 to 0.99) and sensitivity (0.42; 95% CI, 0.32 to 0.52) were optimized at a 2.7-fold rise in anti-PsaA antibody concentration. Sensitivity was improved to a maximum of 0.50 by restricting testing to children of <2 years old, by excluding IPD patients who were not sampled on the first day of presentation, and by incorporating high existing antibody concentrations in the analysis. Assay performance was independent of nasopharyngeal carriage of pneumococci at recruitment. This assay improves on existing diagnostic tools for IPD in children but would still leave over half of all cases undetected in epidemiological studies. Effective diagnosis of pneumococcal disease in children is urgently required but poorly served by existing technology.

Age Factors↗

PubMed2005

Differential PsaA-, PspA-, PspC-, and PdB-specific immune responses in a mouse model of pneumococcal carriage.

Larger numbers of pneumococci were detected in the nasal tract compared to the lung, cervical lymph nodes, and spleen 1, 2, 4, 7, 14, and 21 days after nasal challenge with Streptococcus pneumoniae strain EF3030. In this mouse model of pneumococcal carriage, peripheral S. pneumoniae pneumococcal surface adhesin A (PsaA)-specific humoral responses (immunoglobulin G2a [IgG2a] >> IgG1 = IgG2b > IgG3) were significantly higher than pneumococcal surface protein A (PspA)-specific, genetic toxoid derivative of pneumolysin (PdB)-specific, or pneumococcal surface protein C (PspC)-specific serum antibody levels. However, PspA-specific mucosal IgA antibody levels were significantly higher than those against PsaA, PdB, and PspC. In general, both PsaA- and PspA-specific lung-, cervical lymph node-, nasal tract-, and spleen-derived CD4(+) T-cell cytokine (interleukin-4, interleukin-6, granulocyte-macrophage colony-stimulating factor, gamma interferon, and tumor necrosis factor alpha) and proliferative responses were higher than those for either PspC or PdB. Taken together, these findings suggest that PsaA- and PspA-specific mucosal responses as well as systemic humoral and T helper cell cytokine responses are predominantly yet differentially induced during pneumococcal carriage.

Adhesins, Bacterial↗

PubMed2004

Comparison of four polymerase chain reaction assays for specificity in the identification of Streptococcus pneumoniae.

We determined the usefulness of 4 conventional polymerase chain reaction (PCR) assays, lytA, psaA, and two primer sets from the ply gene, for accuracy in the discrimination of nontypeable (NT) Streptococcus pneumoniae from closely related atypical streptococci. The study used 100 strains. We compared the PCR results with laboratory tests that included optochin (ethylhydrocupreine hydrochloride) sensitivity, bile solubility, the Quellung reaction, and AccuProbe (Gen-Probe Inc., San Diego, CA). These latter tests did not discriminate the atypical streptococci from the NT pneumococci. All PCR primer sets amplified the NT pneumococcal isolates in agreement with the other laboratory tests. However, the IA and IB ply primers were positive for 8 of the 16 atypical streptococcal isolates, and the IIA and IIB ply primers amplified all atypical isolates. The psaA primers had only one discrepant result, a positive among the atypical streptococci. The lytA primers were the most specific with 100% specificity for all strains tested.

Adhesins, Bacterial↗

PubMed2004

SARS surveillance during emergency public health response, United States, March-July 2003.

In response to the emergence of severe acute respiratory syndrome (SARS), the United States established national surveillance using a sensitive case definition incorporating clinical, epidemiologic, and laboratory criteria. Of 1,460 unexplained respiratory illnesses reported by state and local health departments to the Centers for Disease Control and Prevention from March 17 to July 30, 2003, a total of 398 (27%) met clinical and epidemiologic SARS case criteria. Of these, 72 (18%) were probable cases with radiographic evidence of pneumonia. Eight (2%) were laboratory-confirmed SARS-coronavirus (SARS-CoV) infections, 206 (52%) were SARS-CoV negative, and 184 (46%) had undetermined SARS-CoV status because of missing convalescent-phase serum specimens. Thirty-one percent (124/398) of case-patients were hospitalized; none died. Travel was the most common epidemiologic link (329/398, 83%), and mainland China was the affected area most commonly visited. One case of possible household transmission was reported, and no laboratory-confirmed infections occurred among healthcare workers. Successes and limitations of this emergency surveillance can guide preparations for future outbreaks of SARS or respiratory diseases of unknown etiology.

Adolescent↗

PubMed2003

Analysis of recombinant acylated pneumococcal surface adhesin A of Streptococcus pneumoniae by mass spectrometry.

Streptococcus pneumoniae pneumococcal surface adhesin A (PsaA) is a species-common, immunogenic surface lipoprotein. In this study, the psaA gene was expressed as a nonfusion acylated protein in an Escherichia coli expression system. Yields of pure recombinant PsaA (rPsaA) were 8-10 mg/liter of fermentation culture. Analysis of rPsaA tryptic digests by HPLC-electrospray mass spectrometry (MS) confirmed 98% of the expected protein sequence. GC/MS data demonstrated very similar acylation of native and rPsaA by C12:0-C22:0 fatty acids, with C16 and C18 predominating. Negative ion electrospray MS/MS analysis of the rPsaA lipid anchor released by Pronase-E confirmed that the structure was based on an N-terminal palmitoylcysteine (Pam(3)Cys). Electrospray MS heterogeneity analysis of intact rPsaA indicated that all of the observed heterogeneity could be accounted for by the fatty acid distributions. The availability of well-characterized rPsaA will facilitate the continued research and development of protein-based vaccines for the prevention of pneumococcal disease.

Adhesins, Bacterial↗

PubMed2003

Inhibition of pneumococcal adherence to human nasopharyngeal epithelial cells by anti-PsaA antibodies.

The role of pneumococcal (Pnc) surface adhesin A (PsaA) in the adherence of Streptococcus pneumoniae (pneumococcus) to host cells is not well defined. We examined the effect of anti-PsaA antibodies in an inhibition of adherence assay using Detroit 562 nasopharyngeal human epithelial cells. Rabbit polyclonal (Pab) anti-recombinant PsaA (rPsaA) sera, a purified mouse monoclonal antibody (MAb) (MAb 6F62G8E12), and 22 healthy adult sera with known anti-PsaA IgG levels (obtained by enzyme-linked immunosorbent assay) were evaluated for their abilities to inhibit Pnc adherence to confluent monolayers (measured as percent reduction in CFU counts compared to those of uninhibited controls). Pnc adherence was dependent on capsular phenotype (no or low adherence for opaque strains). With an inoculum of 10(4) to 10(5) bacteria/well, the mean +/- standard deviation count in controls was 163 +/- 32 CFU/well for transparent strains. Low adherence was observed for a PsaA-minus mutant even at higher inoculum doses. Mean percent inhibitions of adherence with Pab and MAb were 54 and 50%, respectively. Adult sera showed inhibition in a dose-response fashion with a range of 98 to 8%, depending on the serum anti-PsaA antibody concentration. Absorption of Pab with rPsaA restored Pnc adherence to control levels. Absorption of sera with a PsaA-minus mutant did not result in a significant decrease (P >0.05) of inhibition of adherence activity. Additionally, nearly 100% of Pnc adherence was inhibited by lipidated rPsaA at 2.5 micro g/ml. Our data support the argument that PsaA is an adhesin that mediates Pnc adherence to human nasopharyngeal cells. This functional assay may be useful in evaluating antibodies elicited in response to PsaA vaccination.

Adhesins, Bacterial↗