Immunological efficiency of Haemophilus influenzae type b polyribosyl ribitol phosphate combined with detoxified lipooligosaccharide in a rabbit model
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Abstract
Background and Objectives: Haemophilus influenzae type b (Hib) could cause severe life-threatening infections in children. Combine vaccines have reduced invasive diseases, but disease management is still necessary. The aim of this research was to evaluate the immunological efficiency of polyribosyl-ribitol-phosphate combined with detoxified lipooligosaccharide (PRP-dLOS) in a rabbit model.
Materials and Methods: PRP purification, LOS extraction, and endotoxin evaluation were performed using modified CY medium, hot phenol, and limulus amebocyte lysate methods, respectively. Rabbit groups were immunized with PRP (10 µg), dLOS (20 µg), and PRP-dLOS combine (10 µg+20 µg) three times on days 0, 14, and 28. Serum samples were acquired on days 0, 14, and 28 post-immunization, then IgM and IgG levels were assayed by enzyme-linked immunosorbent assay.
Results: The concentrations of PRP, dLOS, and endotoxin were 1160 mg/L, 440 μg/mL, and 1450 EU/mL, respectively. PRP-dLOS combine led to a significant increase in IgG and IgM levels on days 14 and 28 post-immunization. After immunization with PRP-dLOS combine, serum levels of IgM and IgG increased from 16.8 to 29.3 µg/mL and 29.8 to 61.4 µg/mL, respectively from day 14 to day 28.
Conclusion: PRP-dLOS combine is a promising approach for Hib management without the fear of delay in immune responses and interference with other vaccines.
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16. Arsang A, Tabatabaie A, Vaziri F, Nejati M, Zolfaghari MR, Fateh A, et al. Optimization of large scale production of Haemophilus influenzae type b polyribosyl-ribitol phosphate. Minerva Biotecnol 2017; 29: 17-23.
17. Arsang A, Yari S, Masoumi M, Neamatollahi AN, Vaziri F, Nejati M, et al. Extraction and purification of haemophilus influenzae type b lipooligosaccharide by Modified Phenol method. Vac Res 2014; 1: 28-30.
18. Rezania S, Amirmozaffari N, Tabarraei B, Jeddi-Tehrani M, Zarei O, Alizadeh R, et al. Extraction, purification and characterization of lipopolysaccharide from Escherichia coli and Salmonella typhi. Avicenna J Med Biotechnol 2011; 3: 3-9.
19. Long J, Zhao X, Liang F, Zeng Y, Liu N, Sun Y, et al. An innovative lab-scale production for a novel therapeutic DNA vaccine candidate against rheumatoid arthritis. J Biol Eng 2024; 18: 19.
20. Cross AS, Opal SM, Palardy JE, Drabick JJ, Warren HS, Huber C, et al. Phase I study of detoxified Escherichia coli J5 lipopolysaccharide (J5dLPS)/group B meningococcal outer membrane protein (OMP) complex vaccine in human subjects. Vaccine 2003; 21: 4576-4587.
21. Ahmadi-Noorbakhsh S, Mirabzadeh Ardakani E, Sadighi J, Aldavood SJ, Farajli Abbasi M, Farzad-Mohajeri S, et al. Guideline for the care and use of laboratory animals in Iran. Lab Anim (NY) 2021; 50: 303-305.
22. Hassan MA, Abd Elkawi M, Saber M, Senosy W, Nassif M, ElSherif M. Evaluation of xylazine ketamine anesthesia in rabbits undergoing tendon surgery: A prospective randomized controlled study. New Valley Vet J 2024; 4: 10.21608/nvvj.2023.247402.1038.
23. Hutter J, Pasetti MF, Sanogo D, Tapia MD, Sow SO, Levine MM. Naturally acquired and conjugate vaccine-induced antibody to Haemophilus influenzae type b (Hib) polysaccharide in Malian children: serological assessment of the Hib immunization program in Mali. Am J Trop Med Hyg 2012; 86: 1026-1031.
24. Howie SR. Global Hib vaccination: reasons to cheer and fear. Lancet Glob Health 2016; 4(3): e142-e143.
25. He Y, Zhao Y, Liang H, Wang X, Lan H, Tian D, et al. Systematic evaluation of the distribution of immune cells following subcutaneous administration of Haemophilus influenzae type B vaccine to mice. Diseases 2023; 11: 139.
26. Perrett KP, John TM, Jin C, Kibwana E, Yu L-M, Curtis N, et al. Long-term persistence of immunity and B-cell memory following Haemophilus influenzae type B conjugate vaccination in early childhood and response to booster. Clin Infect Dis 2014; 58: 949-959.
2. Park JJ, Narayanan S, Tiefenbach J, Lukšić I, Ale BM, Adeloye D, et al. Estimating the global and regional burden of meningitis in children caused by Haemophilus influenzae type b: A systematic review and meta-analysis. J Glob Health 2022; 12: 04014.
3. Harrison A, Mason KM (2015). Pathogenesis of Haemophilus influenzae in humans. in: Human Emerging and Re‐emerging Infections: Viral and Parasitic Infections, Volume 1. pp. 517-533.
4. Tchoupa AK, Lichtenegger S, Reidl J, Hauck CR. Outer membrane protein P1 is the CEACAM‐binding adhesin of Haemophilus influenzae. Mol Microbiol 2015; 98: 440-455.
5. Choi J, Cox AD, Li J, McCready W, Ulanova M. Activation of innate immune responses by Haemophilus influenzae lipooligosaccharide. Clin Vaccine Immunol 2014; 21: 769-776.
6. Zariri A, van der Ley P. Biosynthetically engineered lipopolysaccharide as vaccine adjuvant. Expert Rev Vaccines 2015; 14: 861-876.
7. Gao S, Jin W, Quan Y, Li Y, Shen Y, Yuan S, et al. Bacterial capsules: Occurrence, mechanism, and function. NPJ Biofilms Microbiomes 2024; 10: 21.
8. Khattak ZE, Anjum F (2023). Haemophilus influenzae Infection. In: StatPearls. Treasure Island (FL): StatPearls Publishing.
9. Hallström T, Riesbeck K. Haemophilus influenzae and the complement system. Trends Microbiol 2010; 18: 258-265.
10. Rodriguez RS, Mascarenas C, Conde-Glez CJ, Inostroza J, Villanueva S, Velázquez ME, et al. Serological protection induced by Haemophilus influenzae type B conjugate vaccine in Mexican children: is a booster dose of the vaccine needed? Clin Vaccine Immunol 2010; 17: 1639-1641.
11. Kim KH, Lee H, Chung EH, Kang JH, Kim JH, Kim JS, et al. Immunogenicity and safety of two different Haemophilus influenzae type b conjugate vaccines in Korean infants. J Korean Med Sci 2008; 23: 929-936.
12. Gilsdorf JR. Hib vaccines: their impact on Haemophilus influenzae type b disease. J Infect Dis 2021; 224(12 Suppl 2): S321-S330.
13. Khatuntseva EA, Nifantiev NE. Glycoconjugate vaccines for prevention of Haemophilus influenzae type b diseases. Russ J Bioorg Chem 2021; 47: 26-52.
14. Schouls L, Schot C, de Voer RM, van der Klis F, Knol M, Tcherniaeva I, et al. Lagging immune response to Haemophilus influenzae serotype b (Hib) conjugate vaccine after the primary vaccination with Hib of Infants in The Netherlands. Vaccines (Basel) 2020; 8: 347.
15. Potts CC, Rodriguez-Rivera LD, Retchless AC, Buono SA, Chen AT, Marjuki H, et al. Antimicrobial susceptibility survey of invasive Haemophilus influenzae in the United States in 2016. Microbiol Spectr 2022; 10(3): e0257921.
16. Arsang A, Tabatabaie A, Vaziri F, Nejati M, Zolfaghari MR, Fateh A, et al. Optimization of large scale production of Haemophilus influenzae type b polyribosyl-ribitol phosphate. Minerva Biotecnol 2017; 29: 17-23.
17. Arsang A, Yari S, Masoumi M, Neamatollahi AN, Vaziri F, Nejati M, et al. Extraction and purification of haemophilus influenzae type b lipooligosaccharide by Modified Phenol method. Vac Res 2014; 1: 28-30.
18. Rezania S, Amirmozaffari N, Tabarraei B, Jeddi-Tehrani M, Zarei O, Alizadeh R, et al. Extraction, purification and characterization of lipopolysaccharide from Escherichia coli and Salmonella typhi. Avicenna J Med Biotechnol 2011; 3: 3-9.
19. Long J, Zhao X, Liang F, Zeng Y, Liu N, Sun Y, et al. An innovative lab-scale production for a novel therapeutic DNA vaccine candidate against rheumatoid arthritis. J Biol Eng 2024; 18: 19.
20. Cross AS, Opal SM, Palardy JE, Drabick JJ, Warren HS, Huber C, et al. Phase I study of detoxified Escherichia coli J5 lipopolysaccharide (J5dLPS)/group B meningococcal outer membrane protein (OMP) complex vaccine in human subjects. Vaccine 2003; 21: 4576-4587.
21. Ahmadi-Noorbakhsh S, Mirabzadeh Ardakani E, Sadighi J, Aldavood SJ, Farajli Abbasi M, Farzad-Mohajeri S, et al. Guideline for the care and use of laboratory animals in Iran. Lab Anim (NY) 2021; 50: 303-305.
22. Hassan MA, Abd Elkawi M, Saber M, Senosy W, Nassif M, ElSherif M. Evaluation of xylazine ketamine anesthesia in rabbits undergoing tendon surgery: A prospective randomized controlled study. New Valley Vet J 2024; 4: 10.21608/nvvj.2023.247402.1038.
23. Hutter J, Pasetti MF, Sanogo D, Tapia MD, Sow SO, Levine MM. Naturally acquired and conjugate vaccine-induced antibody to Haemophilus influenzae type b (Hib) polysaccharide in Malian children: serological assessment of the Hib immunization program in Mali. Am J Trop Med Hyg 2012; 86: 1026-1031.
24. Howie SR. Global Hib vaccination: reasons to cheer and fear. Lancet Glob Health 2016; 4(3): e142-e143.
25. He Y, Zhao Y, Liang H, Wang X, Lan H, Tian D, et al. Systematic evaluation of the distribution of immune cells following subcutaneous administration of Haemophilus influenzae type B vaccine to mice. Diseases 2023; 11: 139.
26. Perrett KP, John TM, Jin C, Kibwana E, Yu L-M, Curtis N, et al. Long-term persistence of immunity and B-cell memory following Haemophilus influenzae type B conjugate vaccination in early childhood and response to booster. Clin Infect Dis 2014; 58: 949-959.
| Files | ||
| Issue | Vol 17 No 1 (2025) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v17i1.17807 | |
| Keywords | ||
| Haemophilus influenzae type b; Immunological; Lipooligosaccharide; Meningitis | ||
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How to Cite
1.
Arsang A, Siadat SD, Saberpour M, Nojoomi F. Immunological efficiency of Haemophilus influenzae type b polyribosyl ribitol phosphate combined with detoxified lipooligosaccharide in a rabbit model. Iran J Microbiol. 2025;17(1):106-112.
