Studying the Effects of Naloxone-Alum Adjuvant Mixture on Cytokines in Model of Multi- Epitope Vaccine in HIV-1

Subject Areas : Journal of Chemical Health Risks

Meimanat Fathi ¹ , Reza Nezamzadeh ² , Mehdi Mahdavi ³

1 -
2 -
3 -

Received: 2014-06-14 Accepted : 2018-10-29 Published : 2018-10-29

Keywords: cytokines, Alum, HIV-1, Naloxone,

Abstract :

Cytokines have important roles in the control of bacterial and viral infections such as HIV-1. Interleukin 17 which is secreted by Th17 is one of these cytokines with a special role in controlling microbial infections. In the present study, adjuvant activity of Alum and Naloxone mixture has been studied on immune responses, especially IL-17 cytokine. Naloxone and Alum adjuvant are mixed with 10 µg of recombinant vaccine HIV-1-gag-pol-tat-env. Experimental groups, consisting of 36 inbred male Balb/c mice divided into six groups, were injected subcutaneouslyat days 0, 14 and 28 with total volume of 200 µl. 2 weeks after final injection, mouse spleens were removed in sterile conditions and used to prepare suspensions. Lymphocyte proliferation responses were evaluated with Brdu test and evaluation of cytokines IL-4, IL-17 and INF-γ were completed using ELISA kit, plus total antibody and antibody isotopes IgG1 and IgG2a using ELISA test. All results show that the mixture of Alum with Naloxone increased cellular immune parameters and specially raised interleukin 17 which illustrated a significant difference with other groups. It seems that Alum and Naloxone mixture could control viral infections by affecting the Th17 pathway in which IL17 cytokine has a critical role.

References:

1. Barouch D.H., Korber B., 2010. HIV-1 vaccine development after STEP. Annual Review of Medicine. 61,153-67.
2. Klein F., Mouquet H., Dosenovic P., Scheid J.F., Scharf L., Nussenzweig M.C., 2013. Antibodies in HIV-1 Vaccine Development and Therapy. Science. 341(6151):1199-204.
3. Aucouturier J., Dupuis L., Ganne V., 2001. Adjuvants designed for veterinary and human vaccines. Vaccine.19(17-19):2666-72.
4. Petrovsky N., Aguilar J.C., 2004.Vaccine adjuvants: Current state and future trends. Immunology and Cell Biology. 82(5): 488-96.
5. Aguilar J.C., Rodríguez E.G., 2007. Vaccine adjuvants revisited. Vaccine. 25(19):3752-62.
6. Lima K.M., dos Santos S.A., Rodrigues J.J., Silva C.L., 2004.Vaccine adjuvant: it makes the difference. Vaccine. 22(19): 2374-9.
7. Mbow M.L., De Gregorio E., Ulmer J.B., 2011. Alum's adjuvant action: grease is the word. Nature Medicine.17(4):415ââ‚‌“6.
8. Tomljenovic L., Shaw C.A., 2011. Aluminum vaccine adjuvants: are they safe? Current Medicinal Chemistry.18(17):2630-7.
9. Lindblad E.B., 2004. Aluminium compounds for use in vaccines. Immunology and Cell Biology. 82(5):497ââ‚‌“505.
10. Jamali A., Mahdavi M., Hassan Z.M., Sabahi F., Farsani M.J., Bamdad, 2009. A novel adjuvant, the general opioid antagonist naloxone, elicits a robust cellular immune response for a DNA vaccine. International Immunology. 21(3): 217-25.
11. Jamali A., Mahdavi M., Shahabi S., Hassan Z.M., Sabahi F., Javan M., 2007. Naloxone, an opioid receptor antagonist, enhances induction of protective immunity against HSV-1 infection in BALB/c mice. Microbial Pathogenesis.43(5-6): 217ââ‚‌“23.
12. Jazani N.H., Sohrabpour M., Mazloomi E., Shahabi S., 2011. A novel adjuvant, a mixture of alum and the general opioid antagonist naloxone, elicits both humoral and cellular immune responses for heat-killed Salmonella typhimurium vaccine. FEMS Immunology and Medical Microbiology. 61(1):54ââ‚‌“62.
13. Jazani N.H., Karimzad M., Mazloomi E., Sohrabpour M., Hassan Z.M., Ghasemnejad H., 2010. Evaluation of the adjuvant activity of naloxone, an opioid receptor antagonist, in combination with heat-killed Listeria monocytogenes vaccine. Microbes and Infection.12(5): 382ââ‚‌“8.
14. Jazani N.H., Parsania S., Sohrabpour M., Mazloomi E., Karimzad M., Shahabi S., 2011. Naloxone and alum synergistically augment adjuvant activities of each other in a mouse vaccine model of Salmonella typhimurium infection. Immunobiology. 216(6): 744ââ‚‌“51.
15. Xu Y.F., Fu L.L., Jiang C.H., Qin Y.W., Ni Y.Q., Fan J.W., 2012. Naloxone Inhibition of Lipopolysaccharide-Induced Activation of Retinal Microglia is Partly Mediated via the p38 Mitogen Activated Protein Kinase Signalling Pathway International Medical Research. 40(4): 1438 ââ‚‌“ 48.
16. Tsai R.Y., Tai Y.H., Tzeng J.I., Lin S.L., Shen C.H., Yang C.P., 2009. Ultra-low dose naloxone restores the antinociceptive effect of morphine in pertussis toxinââ‚‌“treated rats and prevents glutamate transporter downregulation by suppressing the p38 mitogen-activated protein kinase signaling pathway. Neuroscience. 159(4):1244ââ‚‌“56.
17. Moore S.F., MacKenzie A.B., 2009. NADPH oxidase NOX2 mediates rapid cellular oxidation following ATP stimulation of endotoxin-primed macrophages. The Journal of Immunology. 183(5):3302-8. Epub 2009/08/22.
18. Lee K., Won H.Y., Bae M.A., Hong J.H., Hwang E.S., 2011. Spontaneous and aging-dependent development of arthritis in NADPH oxidase 2 deficiency through altered differentiation of CD11b+ and Th/Treg cells. Proceedings of the National Academy of Sciences.108(23):ÂÂ‌ÂÂ‌ÂÂ‌ÂÂ‌ÂÂ‌ÂÂ‌9548-53. Epub 2011/05/20.
19. Shebl F.M., Yu K., Landgren O., Goedert J.J., Rabkin C.S., 2012. Increased Levels of Circulating Cytokines with HIV-Related Immunosuppression AIDS Research and Human Retroviruses. 28(8): 809-5.
20. Wijesundara D.K., Jackson R.J., Tscharke D.C., Ranasinghe C., 2013. IL-4 and IL-13 mediated down-regulation of CD8 expression levels can dampen anti-viral CD8+ T cell avidity following HIV-1 recombinant pox viral vaccination. Vaccine. 31(41): 4548ââ‚‌“55.
21. Chevalier M.F., Petitjean G., Dunyach-Rémy C., Didier C., Girard P.M., Manea M.E., 2013. The Th17/Treg Ratio, IL-1RA and sCD14 Levels in Primary HIV Infection Predict the T-cell Activation Set Point in the Absence of Systemic Microbial Translocation PLOS Pathogens. 9(6): e1003453.
22. Pal R., Wang S., Kalyanaraman V.S., Nair B.C., Whitney S., Keen T., 2005. Polyvalent DNA prime and envelope protein boost HIV-1 vaccine elicits humoral and cellular responses and controls plasma viremia in rhesus macaques following rectal challenge with an R5 SHIV isolate. Med Primatol. 34(5-6): 226-36.