Recombinant Protein D from Haemophilus influenzae Induces Mouse Bactericidal Antibodies Against Typeable and Non-Typeable Haemophilus influenzae, which Partially Protect Infant Rats Against Serotype b Bacteraemia

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Authors

  • Nathan Palmer Bacteriology Division, National Institute for Biological Standards and Control, MHRA, Potters Bar, Hertfordshire EN6 3QG, UK; Institute of Molecular and Cell Biology, Agency for Science,Technology and Research, Proteos 138673, Singapore
  • Yajun Tan National Institutes for Food and Drug Control, No. 31, Huatuo Road, Bio-Pharmaceutical Industrial Base, Daxing District, Beijing, 102629, P. R. China
  • Manolya Saydam Bacteriology Division, National Institute for Biological Standards and Control, MHRA, Potters Bar, Hertfordshire EN6 3QG, UK
  • Arif Felek Bacteriology Division, National Institute for Biological Standards and Control, MHRA, Potters Bar, Hertfordshire EN6 3QG, UK
  • Huajie Zhang National Institutes for Food and Drug Control, No. 31, Huatuo Road, Bio-Pharmaceutical Industrial Base, Daxing District, Beijing, 102629, P. R. China
  • Shumin Zhang National Institutes for Food and Drug Control, No. 31, Huatuo Road, Bio-Pharmaceutical Industrial Base, Daxing District, Beijing, 102629, P. R. China
  • Min Fang Bacteriology Division, National Institute for Biological Standards and Control, MHRA, Potters Bar, Hertfordshire EN6 3QG, UK
  • Jun X. Wheeler Bacteriology Division, National Institute for Biological Standards and Control, MHRA, Potters Bar, Hertfordshire EN6 3QG, UK
  • Qiming Hou National Institutes for Food and Drug Control, No. 31, Huatuo Road, Bio-Pharmaceutical Industrial Base, Daxing District, Beijing, 102629, P. R. China
  • Xiao Ma National Institutes for Food and Drug Control, No. 31, Huatuo Road, Bio-Pharmaceutical Industrial Base, Daxing District, Beijing, 102629, P. R. China
  • Junzhi Wang National Institutes for Food and Drug Control, No. 31, Huatuo Road, Bio-Pharmaceutical Industrial Base, Daxing District, Beijing, 102629, P. R. China
  • Fatme Mawas Bacteriology Division, National Institute for Biological Standards and Control, MHRA, Potters Bar, Hertfordshire EN6 3QG, UK

DOI:

https://doi.org/10.17140/VROJ-5-116

Keywords:

Haemophilus influenzae (Hi), Haemophilus influenzae serotype b bacteraemia, Rats

Abstract

Aim
To evaluate the immunogenicity of a recombinant protein D from Haemophilus Influenzae (Hi) and the functional activities of the
induced protein D antibodies in a mouse model.
Methods
Female Balb/c mice were immunised subcutaneously with recombinant protein D in the presence or absence of adjuvants and the
serum immunoglobulin G (IgG) response to protein D was assessed by ELISA. The functional activity of the immune sera was
evaluated in vitro using bactericidal assay against typeable Hi serotype b (Hib) and non-typeable Hi (NTHi) clinical isolates and in
vivo using an infant rat bacteraemia model and a Hib clinical isolate.
Results
A dose-dependent IgG response was induced in mice immunised with the recombinant protein D and this response was further
increased by the adjuvants used [CPG, AlPO4 and Al(OH)3], with the latter showing the greatest effect on the antibody response.
Immune sera were very effective in bactericidal assay against several Hib and NTHi clinical isolates, with a higher serum bactericidal
titre against the NTHi than against the Hib isolates. This is possibly due to the lower expression of protein D on the Hib isolates
used in our study, compared to the NTHi isolates. In addition, anti-protein D antibodies were partially protective in vivo infant rat
bacteraemia model against a challenge with Hib Eagan strain.
Conclusion
Our results suggest that recombinant protein D is a good vaccine candidate against Hi and should be given in combination with
other vaccine candidates to ensure complete protection against Hib and NTHi.

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Published

2020-02-27

How to Cite

Nathan Palmer, Yajun Tan, Manolya Saydam, Arif Felek, Huajie Zhang, Shumin Zhang, … Fatme Mawas. (2020). Recombinant Protein D from Haemophilus influenzae Induces Mouse Bactericidal Antibodies Against Typeable and Non-Typeable Haemophilus influenzae, which Partially Protect Infant Rats Against Serotype b Bacteraemia. Vaccination Research, 5(1), 1–9. https://doi.org/10.17140/VROJ-5-116

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Vol. 5 No. 1 (2020): Volume 5 Issue 1 2020

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