Evaluation of Cellular Immune Responses in Dogs Immunized with Alum-Precipitated Autoclaved Leishmania major along with BCG and Imiquimod
-
Mohammad Barati
,
Mehdi Mohebali
,
Ali Khamesipour
,
Fariborz Bahrami
,
Haiedeh Darabi
,
Vahid Khaze
,
Farhad Riazi-Rad
,
Gholamreza Habibi
,
Soheila Ajdary
,
Mohammad Hossein Alimohammadian
Abstract
Background: We aimed to investigate the potential effects of BCG and imiquimod on improvement of current experimental L. major vaccine against dogs in an endemic area of Zoonotic visceral leishmaniasis (ZVL) in Iran.
Methods: During 2012 till 2014, seven mixedbreed shepherd dogs with no anti-Leishmania antibodies and no response to Leishmanin reagent were immunized with 2 doses of alum-precipitated autoclaved L. major (Alum-AML) while BCG and imiquimod (for skin pre-treatment) were used as adjuvants. The productions of a few characteristic cytokines of T-helper immune responses and the development of delayed-type hypersensitivity (DTH) of the immunized animals were then evaluated, up to 300 days. Blood samples were collected at 0, 30, 80 and 300 d post-vaccination and the concentrations of IFN-γ, IL10, IL-12 and TGF-β cytokines secreted from PBMCs at these time-points were quantified by ELISA. DTH was evaluated by Leishmanin skin test (LST).
Results: Although a similar LST conversion was observed at all time-points, the cytokine measurement results indicated significantly higher levels of IFN-γ at day 80 and elevated levels of IL-10 at days 80 and 300, post-vaccination. Moreover, a significantly higher IFN-γ/IL-10 ratio was observed at day 30 post-vaccination compared to the other time-points.
Conclusion: Although a Th1-like response could be observed at day 30 post-vaccination, the development of cytokine profiles was inclined toward mixed Th1 and Th2 responses at days 80 and 300 post-vaccination. This situation may indicate the requirement of an additional boosting by this Alum-AML formula, in order to induce long-lasting protection against ZVL.
Alvar J, Velez ID, Bern C, Herrero M, Desjeux P, Cano J, et al. Leishmaniasis worldwide and global estimates of its incidence. PLoS One. 2012;7(5):e35671.
Nadim A S-RM. A brief review of the epidemiology of various types of leishmaniasis in Iran. Acta Med Iran. 1971;XIV:99-106.
Murray HW, Berman JD, Davies CR, Saravia NG. Advances in leishmaniasis. Lancet. 2005;366(9496):1561-77.
Alvar J, Yactayo S, Bern C. Leishmaniasis and poverty. Trends Parasitol. 2006;22(12):552-7.
Otranto D, Dantas-Torres F. The prevention of canine leishmaniasis and its impact on public health. Trends Parasitol. 2013;29(7):339-45.
Moreno J, Alvar J. Canine leishmaniasis: epidemiological risk and the experimental model. Trends Parasitol. 2002;18(9):399-405.
Salahi-Moghaddam A, Mohebali M, Moshfae A, Habibi M, Zarei Z. Ecological study and risk mapping of visceral leishmaniasis in an endemic area of Iran based on a geographical information systems approach. Geospat Health. 2010;5(1):71-7.
Gavgani AS, Ghazanchaei A, Karimi P, Mohit H, Davies CR. Practical approach for typing strains of Leishmania infantum by enzyme polymorphism: a cross sectional study in Northwest of Iran. Pak J Biol Sci. 2007;10(24):4505-9.
Sarkari B, Hatam G, Ghatee M. Epidemiological features of visceral leishmaniasis in fars province, southern iran. Iran J Public Health. 2012;41(4):94-9.
Ashkan MM, Rahim KM. Visceral leishmanisis in paediatrics: a study of 367 cases in southwest Iran. Trop Doct. 2008;38(3):186-8.
Baneth G, Aroch I. Canine leishmaniasis: a diagnostic and clinical challenge. Vet J. 2008;175(1):14-5.
Pinelli E, van der Kaaij SY, Slappendel R, Fragio C, Ruitenberg EJ, Bernadina W, et al. Detection of canine cytokine gene expression by reverse transcription-polymerase chain reaction. Vet Immunol Immunopathol. 1999;69(2-4):121-6.
Reiner SL, Zheng S, Wang ZE, Stowring L, Locksley RM. Leishmania promastigotes evade interleukin 12 (IL-12) induction by macrophages and stimulate a broad range of cytokines from CD4+ T cells during initiation of infection. J Exp Med. 1994;179(2):447-56.
Sypek JP, Chung CL, Mayor SE, Subramanyam JM, Goldman SJ, Sieburth DS, et al. Resolution of cutaneous leishmaniasis: interleukin 12 initiates a protective T helper type 1 immune response. J Exp Med. 1993;177(6):1797-802.
Alves CF, de Amorim IF, Moura EP, Ribeiro RR, Michalick MS, Kalapothakis E, et al. Expression of IFN-gamma, TNF-alpha, IL-10 and TGF-beta in lymph nodes associates with parasite load and clinical form of disease in dogs naturally infected with Leishmania (Leishmania) chagasi. Vet Immunol Immunopathol. 2009;128(4):349-58.
Resende LA, Roatt BM, Aguiar-Soares RD, Viana KF, Mendonca LZ, Lanna MF, et al. Cytokine and nitric oxide patterns in dogs immunized with LBSap vaccine, before and after experimental challenge with Leishmania chagasi plus saliva of Lutzomyia longipalpis. Vet Parasitol. 2013;198(3-4):371-81.
Moreno J, Vouldoukis I, Martin V, McGahie D, Cuisinier AM, Gueguen S. Use of a LiESP/QA-21 vaccine (CaniLeish) stimulates an appropriate Th1-dominated cell-mediated immune response in dogs. PLoS Negl Trop Dis. 2012;6(6):e1683.
Araujo MS, de Andrade RA, Sathler-Avelar R, Magalhaes CP, Carvalho AT, Andrade MC, et al. Immunological changes in canine peripheral blood leukocytes triggered by immunization with first or second generation vaccines against canine visceral leishmaniasis. Vet Immunol Immunopathol. 2011;141(1-2):64-75.
Shahbazi M, Zahedifard F, Taheri T, Taslimi Y, Jamshidi S, Shirian S, et al. Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis. PLoS One. 2015;10(7):e0132794.
Johnston D, Bystryn JC. Topical imiquimod is a potent adjuvant to a weakly-immunogenic protein prototype vaccine. Vaccine. 2006;24(11):1958-65.
Dockrell DH, Kinghorn GR. Imiquimod and resiquimod as novel immunomodulators. J Antimicrob Chemother. 2001;48(6):751-5.
Doxsee CL, Riter TR, Reiter MJ, Gibson SJ, Vasilakos JP, Kedl RM. The immune response modifier and Toll-like receptor 7 agonist S-27609 selectively induces IL-12 and TNF-alpha production in CD11c+CD11b+CD8- dendritic cells. J Immunol. 2003;171(3):1156-63.
Zhang WW, Matlashewski G. Immunization with a Toll-like receptor 7 and/or 8 agonist vaccine adjuvant increases protective immunity against Leishmania major in BALB/c mice. Infect Immun. 2008;76(8):3777-83.
Barati M, Mohebali M, Alimohammadian MH, Khamesipour A, Akhoundi B, Zarei Z. Canine visceral leishmaniasis: seroprevalence survey of asymptomatic dogs in an endemic area of northwestern Iran. J Parasit Dis. 2015;39(2):221-4.
Alimohammadian MH, Hakimi H, Nikseresht MA. The preparation and evaluation of reference leishmanin from Leishmania major for use in man for diagnostic and experimental purposes. Med J Islamic Rep Iran. 1993;7:23-8.
Sokal JE. Editorial: Measurement of delayed skin-test responses. N Engl J Med. 1975;293(10):501-2.
Sacks D, Noben-Trauth N. The immunology of susceptibility and resistance to Leishmania major in mice. Nat Rev Immunol. 2002;2(11):845-58.
Khalil EA, Musa AM, Modabber F, El-Hassan AM. Safety and immunogenicity of a candidate vaccine for visceral leishmaniasis (Alum-precipitated autoclaved Leishmania major + BCG) in children: an extended phase II study. Ann Trop Paediatr. 2006;26(4):357-61.
Satti IN, Osman HY, Daifalla NS, Younis SA, Khalil EA, Zijlstra EE, et al. Immunogenicity and safety of autoclaved Leishmania major plus BCG vaccine in healthy Sudanese volunteers. Vaccine. 2001;19(15-16):2100-6.
Giunchetti RC, Reis AB, da Silveira-Lemos D, Martins-Filho OA, Correa-Oliveira R, Bethony J, et al. Antigenicity of a whole parasite vaccine as promising candidate against canine leishmaniasis. Res Vet Sci. 2008;85(1):106-12.
| Files | ||
| Issue | Vol 16 No 3 (2021) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijpa.v16i3.7087 | |
| Keywords | ||
| Zoonotic visceral leishmani-asis (ZVL); Alum-ALM vaccine BCG and imiquimod adju-vant Cytokines Leishmanin skin test (LST) | ||
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