Iranian Journal of Allergy, Asthma and Immunology 2017. 16(3):219-227.

The Effect of Oral Levamisole Co-administration on the Level of Immune Response to Hepatitis B Vaccine in Healthy Individuals: A Randomized Clinical Trial
Mousalreza Hosseini, Payman Shalchiantabrizi, Maliheh Dadgarmoghaddam, Saeideh Ahmady-Simab, Azizollah Behjati, Masoumeh Salari

Abstract


Despite its proven efficacy, the hepatitis B vaccine requires improvements in immune enhancement and durability, especially in the elderly. Levamisole, an immune modulator, has been tested as an adjuvant to hepatitis B vaccine in several studies in immune-compromised populations. However, we aimed to evaluate the effect of levamisole on the immune response to hepatitis B vaccine in healthy subjects. In this randomized clinical trial, healthy family members of chronic hepatitis B patients were given twenty-microgram intramuscular injections of hepatitis B vaccine at 0, 1, and 6 months and 50 miligrams of oral  levamisole twice a day for two weeks with every vaccination dose. Serum hepatitis B surface antibody (HBsAb) levels of ultimately 98 individuals were measured one month after the final vaccination dose and compared to those of 119 subjects that received placebo and vaccine with an identical regimen. HBsAb levels >10 mIU/mL were considered protective. The Student’s t-test, Mann-Whitney test, Kruskal–Wallis analysis (quantitative comparison in age groups), Chi-square test, and the Pearson correlation were used to analyze data. p<0.05 was considered significant. Serum HBsAb levels were significantly higher in the test group (p<0.001). All test subjects had levels above 50 mIU/mL (86.7% exceeding 100 mIU/mL). The quantitative response according to age groups was remarkable (p=0.01 and p<0.001 for placebo and levamisole, respectively), while that of gender was insignificant (p=0.9). Unlike HBsAb titers amongst controls, levels in the levamisole group were affected by smoking (p=0.79 and p=0.006, respectively). We conclude that oral levamisole as an adjuvant to the hepatitis B vaccine enhances the anti-HBs antibody in healthy vaccinees. 


Keywords


Immunization; Hepatitis B vaccines; Levamisole

Full Text:

PDF

References


  1. Kubba AK, Taylor P, Graneek B, Strobel S. Non-responders      to hepatitis B vaccination: a review. Commun Dis Public Health. 2003;6(2):106-12.     
  2. World Health Organization. Geneva: World Health      Organization. Date unknown [updated 2015 Jul; cited 2016 Jan 10].      Available from: http://www.who.int/mediacenter/factsheets/fs204/en     
  3. Kalantari H, Davari M, Akbari M, et al. The estimation      of direct medical costs of treating patients with chronic Hepatitis B and      C in Iran. Int J Prev Med. 2012;3:191-6.
  4. Kim WR. Epidemiology of hepatitis B in the United      States. Hepatology. 2009 May;49(5):S28-S34.
  5. Agarwal N, Naik S, Aggarwal R, Singh H, Somani Sk, Kini      D et al. Occult hepatitis B virus infection as a cause of cirrhosis of      liver in a region with intermediate epidemicity. Indian J Gastroenterol.      2003 Jul;22(4):127-31.
  6. Zhang W, Du X, Zhao G, et al. Levamisole is a potential      facilitator for the activation of TH1 responses of the subunit HBV      vaccination. Vaccine. 2009;27(36):4938-46.
  7. Chen LY, Lin YL, Chieng BL. Levamisole enhances immune      response by affecting the activation and maturation of human      monocyte-derived dendritic cells. Clin Exp Immunol. 2008; 151(1):174-81.
  8. Martin RJ, Robertson AP. Mode of action of Levamisole      and Pyrantel, anthelmintic resistance, E153 and Q57. Parasitology. 2007;      134(8):1093-1104.
  9. Sayyad B, Alavian SM, Najafi F. Effects of levamisole as      an adjuvant to hepatitis B vaccine in HIV/AIDS patients: a randomized      controlled trial. Hepat mon. 2012; 12(9):6234.
  10. Sanadgol H, Khoshnoodi M, Mashhadi MA, Forghani MS.      Effect of adding levamisole on seroconversion response to hepatitis B      virus vaccination in hemodialysis patients: a single-center experience. Iran      J Kidney Dis. 2011; 5(5):338-341.
  11. Sali S, Alavian SM, Hajarizadeh B. Effect of levamisole      supplementation on hepatitis B virus vaccination response in hemodialysis      patients. Nephrology. 2008; 13(5):376-9.
  12. Alavian SM, Tabatabaei SV.  Effects of oral levamisole as an      adjuvant to hepatitis B vaccine in adults with end-stage renal disease: a      meta-analysis of controlled clinical trials. Clin Ther. 2010; 32(1):1-10.
  13. Argani H, Akhtarishojaie E. Levamizole enhances immune      responsiveness to intra-dermal and intra-muscular hepatitis B vaccination      in chronic hemodialysis patients. J Immune Based Ther Vaccines. 2006; 4:3.     
  14. Kayatas M. Levamisole treatment enhances protective      antibody response to hepatitis B vaccination in hemodialysis patients. Int      J Artif Organs. 2002; 26(6):492-6.
  15. Chang A, Osterloh J, Thomas J. Levamisole: A dangerous      new cocaine adulterant. Clin Pharmacol Ther. 2010. 88(3): 408–11.
  16. Wolford A, McDonald TS, Eng H, Hansel S, Chen Y, Bauman      J, et al. Immune-mediated agranulocytosis caused by the cocaine adulterant      levamisole: a case for reactive metabolite(s) involvement. Drug Metab      Dispos. 2012; 40(6):1067-75.
  17. Hepatitis B foundation: cause for a cure [Internet]. Pennsylvania:      Hepatitis B Foundation. 2003 (updated 2009; cited 2014 July 29]. Available      from: http://www.hepb.org/professionals/vaccine_non-responders.htm     
  18. Platkov E, Shlyakhov E, Glick V, Khalemsky S, Fischbein A. Humoral immune response of hospital employees      induced by a recombinant hepatitis b vaccine: 5 years after the primary      standard immunization. J Prev Med. 2001; 9(3):59-66.
  19. Mast EE, Weinbaum CM, Fiore AE, Alter MJ, Bell BP,      Finelli L, et al. Centers for Disease Control and Prevention. Washington:      Centers for Disease Control and Prevention; date unknown [updated 2006 nov      21; cited 2014 August 4]  Available from:       http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5516a1.htm?s_cid=rr5516a1_e#top     
  20. Authors unknown. Are booster immunizations needed for      lifelong hepatitis B immunity? European Consensus Group on Hepatitis B      Immunity. Lancet [Internet]. 2000 [cited 2014 Aug 2];355:561-565.      Available from Pubmed: http://www.ncbi.nlm.nih.gov     
  21. Center for Diseases Control and Prevention. Washington:      Center for Diseases Control and Prevention; date unknown [updated 2001 Apr      21; cited 2014 Aug 2] Available from: http://www.cdc.gov/mmwr/preview/mmwrhtml     
  22. Coursaget P, Leboulleux D, Soumare M, le Cann P, Yvonnet      B, Chiron JP, et al. Twelve-year follow-up study of hepatitis B      immunization of Senegalese infants. J Hepatol. 1994 Aug;21(2):250-4.
  23. Da Villa G, Pelliccia MG, Peluso F, Ricciardi E, Sepe A.      Anti-HBs responses in children vaccinated with different schedules of      either plasma-derived or HBV DNA recombinant vaccine. Research in Virology.      1997; 148(2):109-14.
  24. Looney RJ, Hasan MS, Coffin D, Campbell D, Falsey AR,      Kolassa J, et al. Hepatitis B immunization of healthy elderly adults:      relationship between naïve CD4+ T cells and primary immune response and      evaluation of GM-CSF as an adjuvant. J Clin Immunol. 2001 Jan;21(1):30-6.
  25. Ibrahim S, El-Din S, Bazzal I. Antibody level after      hepatitis-B vaccination in hemodialysis patients: impact of dialysis adequacy,      chronic inflammation, local endemicity and nutritional status. J Natl Med      Assoc. 2006; 98(12):1953-7.
  26. Al Saran K, Sabry A, Al Halawany Z, Ismail M. Factors      affecting response to hepatitis B vaccine among hemodialysis patients in a      large Saudi Hemodialysis Center.Saudi J Kidney Dis Transpl. 2014; 25(1):185-91.     
  27. Schillie S, Murphy TV, Sawyer M, Ly K, Hughes E, Jiles      R, et al. Center for Diseases Control and Prevention. Washington: Center      for Diseases Control and Prevention; date unknown [updated 2001 Apr 21;      cited 2014 Aug 10]. Available from:         http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6210a1.htm         
  28. Winter AP, Follett EA, McIntyre J, Stewart J, Symington      IS. Influence of smoking on immunological responses to hepatitis B      vaccine. Vaccine. 1994; 12(9):771-2.
  29. Shaw FE Jr1, Guess HA, Roets JM, et al. Effect of      anatomic injection site, age and smoking on the immune response to      hepatitis B vaccination. Vaccine. 1989; 7(5):425-30.

 


Refbacks

  • There are currently no refbacks.


Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.