Construction and assessment of the immunogenicity and bactericidal activity of fusion protein porin A from Neisseria meningitidis serogroups A and B admixed with OMV adjuvant as a novel vaccine candidate

Document Type : Original Article

Authors

1 Department of Mycobacteriology & Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran

2 Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran

3 Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran

4 Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Objective(s): The porins A and B and also outer membrane vesicles (OMVs) of Neisseria meningitidis are used for vaccine purposes. In the present study, we aimed to design a new vaccine candidate based on a fusion of PorA of serogroups A and B of N. meningitidis admixed with OMV and evaluate it in an animal model.
Materials and Methods: After bioinformatic studies, a fusion protein composed of porin A from both serogroups A and B of N. meningitidis was constructed, expressed, and purified by nickel resins. Extraction of OMV of N. meningitidis was performed using a chemical method. The mice were vaccinated subcutaneously in different groups with mixtures of PorA proteins, OMV, and Freund’s adjuvants. Then, the immune responses were measured using the ELISA method. Finally, serum bactericidal activity (SBA) procedure was applied to assay the activity of the immune responses in mice.
Results: Mice received the PorA protein plus Freund’s adjuvant. Mice vaccinated with PorA fusion of serogroups A+B plus Freund’s adjuvant produced more IgG, IgG1, and IgG2a than combinations admixed with OMV. Furthermore, the vaccinated mice tended to direct the IgG responses toward IgG1. Sera of the mice that received PorA+Freund’s and those that received PorA+OMV produced higher bactericidal activity than the controls.
Conclusion: Fusion protein porin A could be a valuable target for developing vaccines against N. meningitidis. Although, Freund’s adjuvant induced the strongest IgG responses, given that Freund’s adjuvant has no human use, and OMV is a human adjuvant, OMV could be considered in vaccine design against N. meningitidis.

Keywords

References

1. Tzeng YL, Stephens DS. Epidemiology and pathogenesis of Neisseria meningitidis. Microbes Infect 2000; 2:687-700.
2. Rouphael NG, Stephens DS. Neisseria meningitidis: biology, microbiology, and epidemiology.  Neisseria meningitidis: Springer; 2012. p. 1-20.
3. Oster P, Lennon D, O’Hallahan J, Mulholland K, Reid S, Martin D. MeNZB™: A safe and highly immunogenic tailor-made vaccine against the New Zealand Neisseria meningitidis serogroup B disease epidemic strain. vaccine 2005; 23:2191-2196.
4. Schwartz RH. Historical overview of immunological tolerance. Cold Spring Harb Perspect Biol 2012:a006908.
5. Mari ER, Moore JN, Zhang GX, Rostami A. Mechanisms of immunological tolerance in central nervous system inflammatory demyelination. J Clin Exp Immunol 2015; 6:264-274.
6. Masignani V, Comanducci M, Giuliani MM, Bambini S, Adu-Bobie J, Aricò B, et al. Vaccination against Neisseria meningitidis using three variants of the lipoprotein GNA1870.
Int J Clin Exp Med 2003; 197:789-799.
7. Holst J, Martin D, Arnold R, Huergo CC, Oster P, O’Hallahan J, et al. Properties and clinical performance of vaccines containing outer membrane vesicles from Neisseria meningitidis. Vaccine 2009; 27:B3-B12.
8. Cartwright K, Morris R, Rümke H, Fox A, Borrow R, Begg N, et al.  Immunogenicity and reactogenicity in UK infants of a novel meningococcal vesicle vaccine containing multiple class 1 (PorA) outer membrane proteins. Vaccine 1999; 17:2612-2619.
9. Schwechheimer C, Kuehn MJ. Outer-membrane vesicles from g-negative bacteria: Biogenesis and functions. Nat Rev Microbiol 2015; 13:605-619.
10. Kuehn MJ, Kesty NC. Bacterial outer membrane vesicles and the host–pathogen interaction. Genes & development 2005; 19:2645-2655.
11. Ferrari G, Garaguso I, Adu‐Bobie J, Doro F, Taddei AR, Biolchi A, et al. Outer membrane vesicles from group B Neisseria meningitidis Δgna33 mutant: Proteomic and immunological comparison with detergent‐derived outer membrane vesicles. Proteomics 2006; 6:1856-1866.
12. Ellis TN, Kuehn MJ. Virulence and immunomodulatory roles of bacterial outer membrane vesicles. Microbiol Mol Biol Rev 2010; 74:81-94.
13. Kulp A, Kuehn MJ. Biological functions and biogenesis of secreted bacterial outer membrane vesicles. Annu Rev Microbiol 2010; 64:163-184.
14. Russell JE, Jolley KA, Feavers IM, Maiden MC, Suker J. PorA variable regions of Neisseria meningitidis. Emerg Infect Dis 2004; 10:674.
15. MacDonald IA, Kuehn MJ. Stress-induced outer membrane vesicle production by Pseudomonas aeruginosa. J Bacteriol 2013; 195:2971-2981.
16. Afrough P, Bouzari S, Mousavi SF, Karam MRA, Vaziri F, Fateh A, et al Evaluation of immunological responses to recombinant porin A protein (rPoA) from native strains of Neisseria meningitidis serogroups A and B using OMV as an adjuvant in BALB/c mice. Microbial Pathogenesis 2017; 112:209-214.
17. Siadat S, Behzadiannejad Q, Tabaraie B, Ahmadi H, Norouziuan D, Najar-Peerayeh S, et al. Evaluation of serum bactericidal activity specific for Neisseria meningitidis serogroup A and B: effect of immunization with Neisseria meningitidis serogroup A polysaccharide and serogroup B outer membrane vesicle conjugate as a bivalent meningococcus vaccine candidate. Res J Microbiol 2007; 2:436-444.
18. Brandtzaeg P, van Deuren M. Classification and pathogenesis of meningococcal infections.  Neisseria meningitidis: Springer; 2012. p. 21-35.
19. Taha M-K. Molecular detection and characterization of Neisseria meningitidis. Expert Rev Mol Diagn 2002; 2:143-150.
20. Martin S, Borrow R, Van der Ley P, Dawson M, Fox A, Cartwright K. Effect of sequence variation in meningococcal PorA outer membrane protein on the effectiveness of a hexavalent PorA outer membrane vesicle vaccine. Vaccine 2000; 18:2476-2481.
21. de Kleijn E, van Eijndhoven L, Vermont C, Kuipers B, van Dijken H, Rümke H, et al .Serum bactericidal activity and isotype distribution of antibodies in toddlers and school children after vaccination with RIVM hexavalent PorA vesicle vaccine. Vaccine 2001; 20:352-358.
22. Girard MP, Preziosi M-P, Aguado M-T, Kieny MP. A review of vaccine research and development: meningococcal disease. Vaccine 2006; 24:4692-4700.
23. Serruto D, Bottomley MJ, Ram S, Giuliani MM, Rappuoli R. The new multicomponent vaccine against meningococcal serogroup B, 4CMenB: immunological, functional and structural characterization of the antigens. Vaccine 2012; 30: 87-97.
24. Morley SL, Pollard AJ. Vaccine prevention of meningococcal disease, coming soon? Vaccine 2001; 20:666-687.
25. van der Pol L, Stork M, van der Ley P. Outer membrane vesicles as platform vaccine technology. Biotechnol j 2015; 10:1689-1706.
26. Pizza M, Scarlato V, Masignani V, Giuliani MM, Aricò B, Comanducci M, et al. Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. Science 2000; 287:1816-1820.
27. Reed SG, Orr MT, Fox CB. Key roles of adjuvants in modern vaccines. Nature medicine 2013; 19:1597.
28. Donnelly J, Medini D, Boccadifuoco G, Biolchi A, Ward J, Frasch C, et al. Qualitative and quantitative assessment of meningococcal antigens to evaluate the potential strain coverage of protein-based vaccines. Proc Natl Acad Sci U S A 2010; 107:19490-19495.
29. Giuliani MM, Adu-Bobie J, Comanducci M, Aricò B, Savino S, Santini L, et al. A universal vaccine for serogroup B meningococcus. Proc Natl Acad Sci U S A 2006; 103:10834-10839.
30. Mann B, Thornton J, Heath R, Wade KR, Tweten RK, Gao G, et al. Broadly protective protein-based pneumococcal vaccine composed of pneumolysin toxoid–CbpA peptide recombinant fusion protein. J Infect Dis 2013; 209:1116-1125.
31. Filatova M, Kotel’nikova O, Chibiskova O, Lakhtina O, Nesmeyanov V, Alliluev A, et al. Synthesis and biological properties of polysaccharide-peptide conjugates as potential antigens for a vaccine against meningococci of serogroups A and B. Russ J Bioorganic Chem 2008; 34:563-570.
32. Granoff DM. Relative importance of complement-mediated bactericidal and opsonic activity for protection against meningococcal disease. Vaccine 2009; 27:B117-B125.
33. Tan LK, Carlone GM, Borrow R. Advances in the development of vaccines against Neisseria meningitidis. N Engl J Med 2010; 362:1511-1520.



Iranian Journal of Basic Medical Sciences
Volume 23, Issue 6
June 2020
Pages 737-743

Files

Share

How to cite

Statistics