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Cross-reactive monoclonal antibodies for diagnosis of pneumococcal meningitis
W D Waltman1, B Gray, L S McDaniel
1Department of Microbiology, University of Alabama, Birmingham 35294.
Abstract:
A diagnostic test for the detection of Streptococcus pneumoniae meningitis was developed using monoclonal antibodies (MAbs) to phosphocholine (PC) and non-PC determinants of pneumococcal teichoic acids. These MAbs do not recognize other bacteria that commonly cause meningitis. By using a dot blot assay, these MAbs were compared with a polyvalent pneumococcal capsular omniserum and an antiserum made to whole cells for their ability to detect pneumococci in infected spinal fluids. An immunoglobulin M (IgM) anti-PC antibody gave a positive reaction with 16 of 22 (73%) pneumococcal culture-positive spinal fluids. One false-positive result out of 45 pneumococcal culture-negative spinal fluids was also observed. D3114/63, an IgM MAb to non-PC determinants of teichoic acids, detected 15 of 22 of the pneumococcal culture-positive spinal fluids with one false-positive result. IgG2b and IgG3 anti-PC MAbs were less efficient than the IgM anti-PC MAb at detecting pneumococci in spinal fluids. Like the IgM anti-PC MAb, omniserum detected 73% of the culture-positive pneumococcal spinal fluids, with one false-positive result. The use of anti-PC or D3114/63 MAbs instead of a pooled serum such as omniserum has several advantages: (i) use of a single cross-reactive antibody rather than 83 pooled antibodies; (ii) possibility of a higher concentration of reactive antibody, which may increase the sensitivity of the test; (iii) a standardized antibody preparation; (iv) ease of preparation of the antibody; and (v) less expense.
Insights
A new diagnostic test for Streptococcus pneumoniae meningitis uses monoclonal antibodies (MAbs) to detect pneumococci in spinal fluid. This method offers advantages over traditional pooled sera for improved meningitis diagnosis.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Meningitis remains a significant cause of mortality and morbidity worldwide.
- Streptococcus pneumoniae is a leading bacterial cause of meningitis.
- Accurate and rapid diagnostic tests are crucial for timely treatment.
Purpose of the Study:
- To develop and evaluate a diagnostic test for Streptococcus pneumoniae meningitis.
- To utilize monoclonal antibodies (MAbs) targeting pneumococcal antigens.
- To compare MAb-based detection with conventional methods in clinical samples.
Main Methods:
- Development of MAbs against phosphocholine (PC) and non-PC determinants of pneumococcal teichoic acids.
- Application of a dot blot assay to detect pneumococci in cerebrospinal fluid (CSF).
- Comparison of MAbs (IgM anti-PC, IgM anti-teichoic acid, IgG anti-PC) with polyvalent pneumococcal antiserum (omniserum).
Main Results:
- An IgM anti-PC MAb detected 73% of S. pneumoniae positive CSF samples with one false positive.
- An IgM MAb to non-PC determinants detected 15/22 (68%) positive CSF samples with one false positive.
- IgM anti-PC MAb and omniserum showed similar sensitivity (73%), but MAbs offer advantages in standardization and cost.
Conclusions:
- Monoclonal antibodies provide a sensitive and specific alternative for detecting Streptococcus pneumoniae in meningitis cases.
- The use of MAbs offers advantages including standardization, ease of preparation, and potential cost-effectiveness.
- Further development of MAb-based diagnostics could improve meningitis detection and patient outcomes.