Evaluation of immunological responses against outer membrane vesicles (OMV) of nontypeable Haemophilus influenzae using MPLA-CpG adjuvant as a vaccine candidate
Abstract
Background and Objectives: Nontypeable Haemophilus influenzae (NTHi) are major causes of non-invasive infections, including otitis media and sinusitis and it can also contribute to respiratory infections of all ages. Currently, there is no licensed vaccine against NTHi commercially available. Many studies have been conducted on the use of OMV as a vaccine against NTHi. The purpose of this study is to achieve an immunogenic vaccine against NTHi.
Materials and Methods: In this study, standard OMV Haemophilus (ATCC49766) with adjuncts CpG and MPLA was used and after infusion into BALB/c mice, the levels of antibodies and cytokines were measured on serum of immunized mice.
Results: The results showed that total IgG antibody and IgG1 and IgG2a isotypes in OMV immunized mice with mixture of CpG-MPLA adjuvant had a significant increase. Also, the results of cytokines (IL-10, IL-4 and IFN-γ) showed that IL-4 had the highest rate.
Conclusion: These findings indicate that OMVs derived from NTHi strains have a high potential to act as a vaccine against NTHi infections.
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11. Han MK, Agusti A, Calverley PM, Celli BR, Criner G, Curtis JL, et al. Chronic obstructive pulmonary disease phenotypes: the future of COPD. Am J Respir Crit Care Med 2010;182:598-604.
12. Smith-Vaughan HC, Chang AB, Sarovich DS, Marsh RL, Grimwood K, Leach AJ, et al. Absence of an important vaccine and diagnostic target in carriage-and disease-related nontypeable Haemophilus influenzae. Clin Vaccine Immunol 2014;21:250-252.
13. King PT, Lim S, Pick A, Ngui J, Prodanovic Z, Downey W, et al. Lung T-cell responses to nontypeable Haemophilus influenzae in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol 2013;131:1314-21.e14.
14. Chu TG, Cachola DRR, Regal MAS, Llamas ACG, Martinez NV, Santos WR. Pneumococcal conjugate vaccine (Non-Typeable Haemophilus influenzae (NTHi) protein D, diphtheria or tetanus toxoid conjugates) in prevention of acute otitis media in children: A Cohort Study. Philipp J Otolaryngol Head Neck Surg 2016;31:13-15.
15. Langereis JD, Stol K, Schweda EK, Twelkmeyer B, Bootsma HJ, de Vries SP, et al. Modified lipooligosaccharide structure protects nontypeable Haemophilus influenzae from IgM-mediated complement killing in experimental otitis media. mBio 2012;3(4):e00079-12.
16. Chang A, Kaur R, Michel LV, Casey JR, Pichichero ME. Haemophilus influenzae vaccine candidate outer membrane protein P6 is not conserved in all strains. Hum Vaccin 2011;7:102-105.
17. Michel LV, Kalmeta B, McCreary M, Snyder J, Craig P, Pichichero ME. Vaccine candidate P6 of nontypable Haemophilus influenzae is not a transmembrane protein based on protein structural analysis. Vaccine 2011;29:1624-1627.
18. Kyd JM, Dunkley ML, Cripps AW. Enhanced respiratory clearance of nontypeable Haemophilus influenzae following mucosal immunization with P6 in a rat model. Infect Immun 1995;63:2931-2940.
19. Roier S, Blume T, Klug L, Wagner GE, Elhenawy W, Zangger K, et al. A basis for vaccine development: Comparative characterization of Haemophilus influenzae outer membrane vesicles. Int J Med Microbiol 2015;305:298-309.
20. Khan MN, Ren D, Kaur R, Basha S, Zagursky R, Pichichero ME. Developing a vaccine to prevent otitis media caused by nontypeable Haemophilus influenzae. Expert Rev Vaccines 2016;15:863-878.
21. Deknuydt F, Nordström T, Riesbeck K. Diversion of the host humoral response: a novel virulence mechanism of Haemophilus influenzae mediated via outer membrane vesicles. J Leukoc Biol 2014;95:983-991.
22. Roier S, Leitner DR, Iwashkiw J, Schild-Prüfert K, Feldman MF, Krohne G, et al. Intranasal immunization with nontypeable Haemophilus influenzae outer membrane vesicles induces cross-protective immunity in mice. PLoS One 2012;7(8):e42664.
23. Lu C, Zhang X, Ma C, Xu W, Gan L, Cui J, et al. Nontypeable Haemophilus influenzae DNA stimulates type I interferon expression via STING signaling pathway. Biochim Biophys Acta Mol Cell Res 2018;1865:665-673.
2. Foxwell AR, Kyd JM, Cripps AW. Nontypeable Haemophilus influenzae: pathogenesis and prevention.
Microbiol Mol Biol Rev 1998;62:294-308.
3. Poolman JT, Bakaletz L, Cripps A, Denoel PA, Forsgren A, Kyd J, et al. Developing a nontypeable Haemophilus influenzae (NTHi) vaccine. Vaccine 2000;19 Suppl 1:S108-15.
4. Morey P, Viadas C, Euba B, Hood DW, Barberán M, Gil C, et al. Relative contributions of lipooligosaccharide inner and outer core modifications to nontypeable Haemophilus influenzae pathogenesis. Infect Immun 2013;81:4100-4111.
5. Sharpe SW, Kuehn MJ, Mason KM. Elicitation of epithelial cell-derived immune effectors by outer membrane vesicles of nontypeable Haemophilus influenzae. Infect Immun 2011;79:4361-4369.
6. Jalalvand F, Riesbeck K. Update on non-typeable Haemophilus influenzae-mediated disease and vaccine development. Expert Rev Vaccines 2018;17:503-512.
7. Leroux-Roels G, Van Damme P, Haazen W, Shakib S, Caubet M, Aris E, et al. Phase I, randomized, observer-blind, placebo-controlled studies to evaluate the safety, reactogenicity and immunogenicity of an investigational non-typeable Haemophilus influenzae (NTHi) protein vaccine in adults. Vaccine 2016;34:3156-3163.
8. 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. Microb Pathog 2017;112:209-214.
9. Behrouzi A, Bouzari S, Siadat SD, Oloomi M, Davari M, Mazaheri H. Evaluation of the immunogenic property of NT H. influenzae protein D with Neisseria meningitidis OMV in BALB/c. J Infect Dev Ctries 2016;10:1345-1351.
10. Moghaddam SJ, Ochoa CE, Sethi S, Dickey BF. Nontypeable Haemophilus influenzae in chronic obstructive pulmonary disease and lung cancer. Int J Chron Obstruct Pulmon Dis 2011;6:113-123.
11. Han MK, Agusti A, Calverley PM, Celli BR, Criner G, Curtis JL, et al. Chronic obstructive pulmonary disease phenotypes: the future of COPD. Am J Respir Crit Care Med 2010;182:598-604.
12. Smith-Vaughan HC, Chang AB, Sarovich DS, Marsh RL, Grimwood K, Leach AJ, et al. Absence of an important vaccine and diagnostic target in carriage-and disease-related nontypeable Haemophilus influenzae. Clin Vaccine Immunol 2014;21:250-252.
13. King PT, Lim S, Pick A, Ngui J, Prodanovic Z, Downey W, et al. Lung T-cell responses to nontypeable Haemophilus influenzae in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol 2013;131:1314-21.e14.
14. Chu TG, Cachola DRR, Regal MAS, Llamas ACG, Martinez NV, Santos WR. Pneumococcal conjugate vaccine (Non-Typeable Haemophilus influenzae (NTHi) protein D, diphtheria or tetanus toxoid conjugates) in prevention of acute otitis media in children: A Cohort Study. Philipp J Otolaryngol Head Neck Surg 2016;31:13-15.
15. Langereis JD, Stol K, Schweda EK, Twelkmeyer B, Bootsma HJ, de Vries SP, et al. Modified lipooligosaccharide structure protects nontypeable Haemophilus influenzae from IgM-mediated complement killing in experimental otitis media. mBio 2012;3(4):e00079-12.
16. Chang A, Kaur R, Michel LV, Casey JR, Pichichero ME. Haemophilus influenzae vaccine candidate outer membrane protein P6 is not conserved in all strains. Hum Vaccin 2011;7:102-105.
17. Michel LV, Kalmeta B, McCreary M, Snyder J, Craig P, Pichichero ME. Vaccine candidate P6 of nontypable Haemophilus influenzae is not a transmembrane protein based on protein structural analysis. Vaccine 2011;29:1624-1627.
18. Kyd JM, Dunkley ML, Cripps AW. Enhanced respiratory clearance of nontypeable Haemophilus influenzae following mucosal immunization with P6 in a rat model. Infect Immun 1995;63:2931-2940.
19. Roier S, Blume T, Klug L, Wagner GE, Elhenawy W, Zangger K, et al. A basis for vaccine development: Comparative characterization of Haemophilus influenzae outer membrane vesicles. Int J Med Microbiol 2015;305:298-309.
20. Khan MN, Ren D, Kaur R, Basha S, Zagursky R, Pichichero ME. Developing a vaccine to prevent otitis media caused by nontypeable Haemophilus influenzae. Expert Rev Vaccines 2016;15:863-878.
21. Deknuydt F, Nordström T, Riesbeck K. Diversion of the host humoral response: a novel virulence mechanism of Haemophilus influenzae mediated via outer membrane vesicles. J Leukoc Biol 2014;95:983-991.
22. Roier S, Leitner DR, Iwashkiw J, Schild-Prüfert K, Feldman MF, Krohne G, et al. Intranasal immunization with nontypeable Haemophilus influenzae outer membrane vesicles induces cross-protective immunity in mice. PLoS One 2012;7(8):e42664.
23. Lu C, Zhang X, Ma C, Xu W, Gan L, Cui J, et al. Nontypeable Haemophilus influenzae DNA stimulates type I interferon expression via STING signaling pathway. Biochim Biophys Acta Mol Cell Res 2018;1865:665-673.
| Files | ||
| Issue | Vol 12 No 5 (2020) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v12i5.4602 | |
| Keywords | ||
| Non typeable Haemophilus influenza; Outer membrane vesicle; Vaccine | ||
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How to Cite
1.
Behrouzi A, Arabi Mianroodi R, Afrough P, Ayadi A, Serajian A. Evaluation of immunological responses against outer membrane vesicles (OMV) of nontypeable Haemophilus influenzae using MPLA-CpG adjuvant as a vaccine candidate. Iran J Microbiol. 2020;12(5):417-423.
