Evaluation of truncated NhhA protein as a candidate meningococcal vaccine antigen

Peak, Ian R., Srikhanta, Yogitha N., Weynants, Vincent E., Feron, Christiane, Poolman, Jan T. and Jennings, Michael P. (2013) Evaluation of truncated NhhA protein as a candidate meningococcal vaccine antigen. PLoS One, 8 9: e72003.1-e72003.9. doi:10.1371/journal.pone.0072003


Author Peak, Ian R.
Srikhanta, Yogitha N.
Weynants, Vincent E.
Feron, Christiane
Poolman, Jan T.
Jennings, Michael P.
Title Evaluation of truncated NhhA protein as a candidate meningococcal vaccine antigen
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-09-01
Sub-type Article (original research)
DOI 10.1371/journal.pone.0072003
Open Access Status DOI
Volume 8
Issue 9
Start page e72003.1
End page e72003.9
Total pages 9
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Formatted abstract
NhhA (Neisseria hia homologue) is an outer membrane protein from Neisseria meningitidis, the causative agent of meningococcal disease. The protein is surface exposed and its expression in a wide range of meningococcal strains suggests it is a promising vaccine candidate. In addition, immunization of mice with outer membrane vesicles of strains that overexpress NhhA in conjunction with one of TbpA, Omp85 or NspA results in synergistic bactericidal responses. We previously showed that the NhhA sequence is highly conserved between strains, with the majority of the differences localized to four distinct variable regions located in the amino-terminal region of the mature protein. In this study, N. meningitidis strains were constructed that over-express wild-type NhhA. Strains expressing truncated versions of NhhA, with deletions from the amino-terminal region that removed the most variable regions, were also made. These expression strains were also modified so that immunodominant, phase- and antigenically-variable outer membrane proteins were not expressed, truncated lipooligosaccharide (LOS) expression was genetically fixed (no phase variability), and capsular polysaccharide expression abolished. Outer membrane vesicles derived from these strains were used to immunize mice. As previously observed, a synergistic effect involving another antigen, TbpA, was required to demonstrate bactericidal activity. The highest bactericidal response against a heterologous strain was obtained with a truncated variant of NhhA. These results indicate that removal of (a) variable region(s) does not reduce bactericidal responses against NhhA, and that bactericidal targets exist in regions other than the variable N-teminus. This provides the basis for future examination of responses against truncated NhhA in protecting against heterologous NhhA strains, and further evaluation of truncated NhhA as a candidate for inclusion in a vaccine against all serogroups of N. meningitidis.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Chemistry and Molecular Biosciences
 
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