Highly Similar Sequences of Mature IgA1 Proteases from Neisseria meningitidis, Neisseria gonorrhoeae and Haemophilus influenzae.

The mature serine-type IgA1 protease from Neisseria meningitidis serogroup B strain H44/76 (IgA1pr1_28-1004) is considered here as the basis for creating a candidate vaccine against meningococcal meningitis. In this work, we examine the primary structure similarity of IgA1 proteases from various strains of a number of Gram-negative bacteria (N. meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae) in order to find a structural groundwork for creating a broad-spectrum vaccine based on fragments of this enzyme. BLAST has shown high similarity between the primary structure of IgA1pr1_28-1004 and hypothetical sequences of mature IgA1 proteases from N. meningitidis (in 1060 out of 1061 examined strains), N. gonorrhoeae (in all 602 examined strains) and H. influenzae (in no less than 137 out of 521 examined strains). For these enzymes, common regions of sequence correspond to IgA1pr1_28-1004 fragments 28-84, 146-193, 253-539, 567-628, 639-795 and 811-1004, with identity of at least 85%. We believe that these fragments can be used in the development of a vaccine to prevent diseases caused by pathogenic strains of N. meningitidis and N. gonorrhoeae as well as a significant number of strains of H. influenzae.

Protective potency of recombinant meningococcal IgA1 protease and its structural derivatives upon animal invasion with meningococcal and pneumococcal infections.

Immunization of mice with recombinant IgA1 protease of Neisseria meningitidis or several structural derivatives thereof protects the animals infected with a variety of deadly pathogens, including N. meningitidis serogroups A, B, and C and 3 serotypes of Streptococcus pneumonia. In sera of rabbits immunized with inactivated pneumococcal cultures, antibodies binding IgA1-protease from N. meningitidis serogroup B were detected. Thus, the cross-reactive protection against meningococcal and pneumococcal infections has been demonstrated in vivo. Presumably it indicates the presence of common epitopes in the N. meningitidis IgA1 protease and S. pneumoniae surface proteins.

A new methodological approach to estimation of IgA1 and IgA2 content in human serum using recombinant IgA1 protease from Neisseria meningitidis.

OBJECTIVES: A new approach to estimation of IgA subclass levels and IgA1/IgA2 ratio using enzymatically active and inactive forms of Neisseria meningitidis IgA1 protease was developed. RESULTS: The approach was tested using the sera of healthy volunteers and patients with meningococcal meningitis. There was a significant increase in the IgA1 level in patients with meningitis (mean titer 1:1546 ± 352) compared to healthy volunteers (mean titer 1:546 ± 282), while the IgA2 content remained unchanged. The IgA1/IgA2 ratio was 6.3 for the healthy volunteers and 12.8 for patients with meningitis. IgA2 for the patients with meningitis and the healthy volunteers were almost unchanged, 1:86 ± 61 and 1:121 ± 46, respectively. CONCLUSIONS: The proposed method is economical and reliable and can be used for evaluation of IgA1 and IgA2 in clinical laboratories or for research purposes.