Skip to main content
Log in

Biogenic Selenium Nanoparticles Synthesized by L. brevis 23017 Enhance Aluminum Adjuvanticity and Make Up for its Disadvantage in Mice

  • Research
  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

The most popular vaccine adjuvants are aluminum ones, which have significantly reduced the incidence and mortality of many diseases. However, aluminum-adjuvanted vaccines are constrained by their limited capacity to elicit cellular and mucosal immune responses, thus constraining their broader utilization. Biogenic selenium nanoparticles are a low-cost, environmentally friendly, low-toxicity, and highly bioactive form of selenium supplementation. Here, we purified selenium nanoparticles synthesized by Levilactobacillus brevis 23017 (L-SeNP) and characterized them using Fourier-transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, scanning electron microscopy, and transmission electron microscopy. The results indicate that the L-SeNP has a particle size ranging from 30 to 200 nm and is coated with proteins and polysaccharides. Subsequently, we assessed the immune-enhancing properties of L-SeNP in combination with an adjuvant-inactivated Clostridium perfringens type A vaccine using a mouse model. The findings demonstrate that L-SeNP can elevate the IgG and SIgA titers in immunized mice and modulate the Th1/Th2 immune response, thereby enhancing the protective effect of aluminum-adjuvanted vaccines. Furthermore, we observed that L-SeNP increases selenoprotein expression and regulates oxidative stress in immunized mice, which may be how L-SeNP regulates immunity. In conclusion, L-SeNP has the potential to augment the immune response of aluminum adjuvant vaccines and compensate for their limitations in eliciting Th1 and mucosal immune responses.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Data Availability

No datasets were generated or analysed during the current study.

References

  1. Brunner R, Jensen-Jarolim E, Pali-Schöll I (2010) The ABC of clinical and experimental adjuvants—a brief overview. Immunol Lett 128(1):29–35

    Article  CAS  PubMed  Google Scholar 

  2. Mcgee MC, August A, Huang W (2021) BTK/ITK dual inhibitors: modulating immunopathology and lymphopenia for COVID-19 therapy. J Leukoc Biol 109(1):49–53

    Article  CAS  PubMed  Google Scholar 

  3. Jiang J, Fisher EM, Hensley SE, Lustigman S, Murasko DM, Shen H (2014) Antigen sparing and enhanced protection using a novel rOv-ASP-1 adjuvant in aqueous formulation with influenza vaccines. Vaccine 32(23):2696–2702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Wu X, Tang S, Wang Z, Ma X, Zhang L, Zhang F, Xiao L, Zhao S, Li Q, Wang Y, Wang Q, Chen K (2022) Immune enhancement by the tetra-peptide hydrogel as a promising adjuvant for an H7N9 vaccine against highly pathogenic H7N9 virus. Vaccines 10(1):130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Orr MT, Khandhar AP, Seydoux E, Liang H, Gage E, Mikasa T, Beebe EL, Rintala ND, Persson KH, Ahniyaz A, Carter D, Reed SG, Fox CB (2019) Reprogramming the adjuvant properties of aluminum oxyhydroxide with nanoparticle technology. NPJ Vaccines 4:1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kim E, Attia Z, Woodfint RM, Zeng C, Kim SH, Steiner HE, Shukla RK, Liyanage NPM, Ghimire S, Li J, Renukaradhya GJ, Satoskar AR, Amer AO, Liu S-L, Cormet-Boyaka E, Boyaka PN (2021) Inhibition of elastase enhances the adjuvanticity of alum and promotes anti-SARS-CoV-2 systemic and mucosal immunity. Proc Natl Acad Sci USA 118(34):e2102435118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Huang Z, Rose AH, Hoffmann PR (2012) The role of selenium in inflammation and immunity: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal 16(7):705–743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Qin S, Huang B, Ma J, Wang X, Zhang J, Li L, Chen F (2015) Effects of selenium-chitosan on blood selenium concentration, antioxidation status, and cellular and humoral immunity in mice. Biol Trace Elem Res 165(2):145–152

    Article  CAS  PubMed  Google Scholar 

  9. Azorín I, Madrid J, Martínez S, López M, López MB, López MJ, Hernández F (2020) Can moderate levels of organic selenium in dairy cow feed naturally enrich dairy products? Animals 10(12):2269

    Article  PubMed  PubMed Central  Google Scholar 

  10. Sheikhalipour M, Esmaielpour B, Behnamian M, Gohari G, Giglou MT, Vachova P, Rastogi A, Brestic M, Skalicky M (2021) Chitosan-selenium nanoparticle (Cs-Se NP) foliar spray alleviates salt stress in bitter melon. Nanomaterials (Basel, Switzerland) 11(3):684

    Article  CAS  PubMed  Google Scholar 

  11. Eszenyi P, Sztrik A, Babka B, Prokisch J (2011) Elemental, nano-sized (100–500 nm) selenium production by probiotic lactic acid bacteria. Int J Biosci Biochem Bioinform 1(2):148–152

    Google Scholar 

  12. Wadhwani SA, Shedbalkar UU, Singh R, Chopade BA (2016) Biogenic selenium nanoparticles: current status and future prospects. Appl Microbiol Biotechnol 100(6):2555–2566

    Article  CAS  PubMed  Google Scholar 

  13. Gautam PK, Kumar S, Tomar MS, Singh RK, Acharya A, Kumar S, Ram B (2017) Selenium nanoparticles induce suppressed function of tumor associated macrophages and inhibit Dalton’s lymphoma proliferation. Biochem Biophys Rep 12:172–184

    PubMed  PubMed Central  Google Scholar 

  14. Mahdavi M, Mavandadnejad F, Yazdi MH, Faghfuri E, Hashemi H, Homayouni-Oreh S, Farhoudi R, Shahverdi AR (2017) Oral administration of synthetic selenium nanoparticles induced robust Th1 cytokine pattern after HBs antigen vaccination in mouse model. J Infect Public Health 10(1):102–109

    Article  PubMed  Google Scholar 

  15. Liu R, Sun W, Sun T, Zhang W, Nan Y, Zhang Z, Xiang K, Yang H, Wang F, Ge J (2023) Nano selenium-enriched probiotic Lactobacillus enhances alum adjuvanticity and promotes antigen-specific systemic and mucosal immunity. Front Immunol 14:1116223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Eszenyi P, Sztrik A, Babka B, Prokisch J (2011) Elemental, Nano-Sized (100–500 nm) Selenium production by probiotic lactic acid bacteria. Int J Biosci Biochem Bioinform 1(2):148–152

    Google Scholar 

  17. Xu C, Qiao L, Guo Y, Ma L, Cheng Y (2018) Preparation, characteristics and antioxidant activity of polysaccharides and proteins-capped selenium nanoparticles synthesized by Lactobacillus casei ATCC 393. Carbohyd Polym 195:576–585

    Article  CAS  Google Scholar 

  18. Lu J, Hou H, Wang D, Leenhouts K, Roosmalen MLV, Sun T, Gu T, Song Y, Jiang C, Kong W, Wu Y (2017) Systemic and mucosal immune responses elicited by intranasal immunization with a pneumococcal bacterium-like particle-based vaccine displaying pneumolysin mutant Plym2. Immunol Lett 187:41–46

    Article  CAS  PubMed  Google Scholar 

  19. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods 25(4):402–408

    Article  CAS  PubMed  Google Scholar 

  20. Boyaka PN (2017) Inducing mucosal IgA: a challenge for vaccine adjuvants and delivery systems. J Immunol 199(1):9–16

    Article  CAS  PubMed  Google Scholar 

  21. Qiao L, Dou X, Yan S, Zhang B, Xu C (2020) Biogenic selenium nanoparticles synthesized by Lactobacillus casei ATCC 393 alleviate diquat-induced intestinal barrier dysfunction in C57BL/6 mice through their antioxidant activity. Food Funct 11(4):3020–3031

    Article  CAS  PubMed  Google Scholar 

  22. Ferro C, Florindo HF, Santos HA (2021) Selenium nanoparticles for biomedical applications: from development and characterization to therapeutics. Adv Healthcare Mater 10(16):e2100598

    Article  Google Scholar 

  23. Varlamova EG, Turovsky EA, Blinova EV (2021) Therapeutic potential and main methods of obtaining selenium nanoparticles. Int J Mol Sci 22(19):10808

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Del Giudice G, Rappuoli R, Didierlaurent AM (2018) Correlates of adjuvanticity: a review on adjuvants in licensed vaccines. Semin Immunol 39:14–21

    Article  PubMed  Google Scholar 

  25. Wang Y, Xie Y, Luo J, Guo M, Hu X, Chen X, Chen Z, Lu X, Mao L, Zhang K, Wei L, Ma Y, Wang R, Zhou J, He C, Zhang Y, Zhang Y, Chen S, Shen L, Chen Y, Qiu N, Liu Y, Cui Y, Liao G, Liu Y, Chen C (2021) Engineering a self-navigated MnARK nanovaccine for inducing potent protective immunity against novel coronavirus. Nano Today 38:101139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Khurana A, Tekula S, Saifi MA, Venkatesh P, Godugu C (2019) Therapeutic applications of selenium nanoparticles. Biomed Pharmacother 111:802–812

    Article  CAS  PubMed  Google Scholar 

  27. Skalickova S, Milosavljevic V, Cihalova K, Horky P, Richtera L, Adam V (2017) Selenium nanoparticles as a nutritional supplement. Nutrition 33:83–90

    Article  CAS  PubMed  Google Scholar 

  28. Kessi J, Hörtensteiner S (2018) Inhibition of bacteriochlorophyll biosynthesis in the purple phototrophic bacteria Rhodospirillumrubrum and Rhodobacter capsulatus grown in the presence of a toxic concentration of selenite. BMC Microbiol 18(1):81

    Article  PubMed  PubMed Central  Google Scholar 

  29. Ullah A, Mu J, Wang F, Chan MWH, Yin X, Liao Y, Mirani ZA, Sebt-E-Hassan S, Aslam S, Naveed M, Khan MN, Khatoon Z, Kazmi MR (2022) Biogenic selenium nanoparticles and their anticancer effects pertaining to probiotic bacteria-a review. Antioxidants (Basel, Switzerland) 11(10):1916

    CAS  PubMed  Google Scholar 

  30. Stenzel T, Dziewulska D, Śmiałek M, Tykałowski B, Kowalczyk J, Koncicki A (2019) Comparison of the immune response to vaccination with pigeon circovirus recombinant capsid protein (PiCV rCP) in pigeons uninfected and subclinically infected with PiCV. PLoS One 14(6):e0219175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wørzner K, Hvannastein J, Schmidt ST, Foged C, Rosenkrands I, Pedersen GK, Christensen D (2021) Adsorption of protein antigen to the cationic liposome adjuvant CAF®01 is required for induction of Th1 and Th17 responses but not for antibody induction. Eur J Pharm Biopharm 165:293–305

    Article  PubMed  PubMed Central  Google Scholar 

  32. Peterson DA, Mcnulty NP, Guruge JL, Gordon JI (2007) IgA response to symbiotic bacteria as a mediator of gut homeostasis. Cell Host Microbe 2(5):328–339

    Article  CAS  PubMed  Google Scholar 

  33. Mantis NJ, Rol N, Corthésy B (2011) Secretory IgA’s complex roles in immunity and mucosal homeostasis in the gut. Mucosal Immunol 4(6):603–611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kim K-H, Kwon Y-M, Lee Y-T, Hwang HS, Kim M-C, Ko E-J, Wang B-Z, Quan F-S, Kang S-M (2018) Virus-like particles presenting flagellin exhibit unique adjuvant effects on eliciting T helper type 1 humoral and cellular immune responses to poor immunogenic influenza virus M2e protein vaccine. Virology 524:172–181

    Article  CAS  PubMed  Google Scholar 

  35. Raahati Z, Bakhshi B, Najar-Peerayeh S (2020) Selenium nanoparticles induce potent protective immune responses against Vibrio cholerae WC vaccine in a mouse model. J Immunol Res 2020:8874288

    Article  PubMed  PubMed Central  Google Scholar 

  36. Zuo T, Cao L, Sun X, Li X, Wu J, Lu S, Xue C, Tang Q (2014) Dietary squid ink polysaccharide could enhance SIgA secretion in chemotherapeutic mice. Food Funct 5(12):3189–3196

    Article  CAS  PubMed  Google Scholar 

  37. Wu M, Xiao H, Liu G, Chen S, Tan B, Ren W, Bazer FW, Wu G, Yin Y (2016) Glutamine promotes intestinal SIgA secretion through intestinal microbiota and IL-13. Mol Nutr Food Res 60(7):1637–1648

    Article  CAS  PubMed  Google Scholar 

  38. Amin PB, Diebel LN, Liberati DM (2007) T-cell cytokines affect mucosal immunoglobulin A transport. Am J Surg 194(1):128–133

    Article  CAS  PubMed  Google Scholar 

  39. Hoffmann FW, Hashimoto AC, Shafer LA, Dow S, Berry MJ, Hoffmann PR (2010) Dietary selenium modulates activation and differentiation of CD4+ T cells in mice through a mechanism involving cellular free thiols. J Nutr 140(6):1155–1161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Qian F, Misra S, Prabhu KS (2019) Selenium and selenoproteins in prostanoid metabolism and immunity. Crit Rev Biochem Mol Biol 54(6):484–516

    Article  CAS  PubMed  Google Scholar 

  41. Xia Y, Hill KE, Li P, Xu J, Zhou D, Motley AK, Wang L, Byrne DW, Burk RF (2010) Optimization of selenoprotein P and other plasma selenium biomarkers for the assessment of the selenium nutritional requirement: a placebo-controlled, double-blind study of selenomethionine supplementation in selenium-deficient Chinese subjects. Am J Clin Nutr 92(3):525–531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Li Q, Chen G, Wang W, Zhang W, Ding Y, Zhao T, Li F, Mao G, Feng W, Wang Q, Yang L, Wu X (2018) A novel Se-polysaccharide from Se-enriched G. frondosa protects against immunosuppression and low Se status in Se-deficient mice. Int J Biol Macromol 117:878–889

    Article  CAS  PubMed  Google Scholar 

  43. Chen Y-C, Sosnoski DM, Gandhi UH, Novinger LJ, Prabhu KS, Mastro AM (2009) Selenium modifies the osteoblast inflammatory stress response to bone metastatic breast cancer. Carcinogenesis 30(11):1941–1948

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Hou L, Qiu H, Sun P, Zhu L, Chen F, Qin S (2020) Selenium-enriched Saccharomyces cerevisiae improves the meat quality of broiler chickens via activation of the glutathione and thioredoxin systems. Poult Sci 99(11):6045–6054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Carlson BA, Yoo M-H, Shrimali RK, Irons R, Gladyshev VN, Hatfield DL, Park JM (2010) Role of selenium-containing proteins in T-cell and macrophage function. Proc Nutr Soc 69(3):300–310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Lyu W, Xiang Y, Wang X, Li J, Yang C, Yang H, Xiao Y (2022) Differentially expressed hepatic genes revealed by transcriptomics in pigs with different liver lipid contents. Oxid Med Cell Longev 2022:2315575

    Article  PubMed  PubMed Central  Google Scholar 

  47. Noh OJ, Park YH, Chung YW, Kim IY (2010) Transcriptional regulation of selenoprotein W by MyoD during early skeletal muscle differentiation. J Biol Chem 285(52):40496–40507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kiełczykowska M, Kocot J, Paździor M, Musik I (2018) Selenium - a fascinating antioxidant of protective properties. Adv Clin Exp Med 27(2):245–255

    Article  PubMed  Google Scholar 

  49. Kamiński MM, Sauer SW, Kamiński M, Opp S, Ruppert T, Grigaravičius P, Grudnik P, Gröne HJ, Krammer PH, Gülow K (2012) T cell activation is driven by an ADP-dependent glucokinase linking enhanced glycolysis with mitochondrial reactive oxygen species generation. Cell Rep 2(5):1300–1315

    Article  PubMed  Google Scholar 

  50. Sena LA, Li S, Jairaman A, Prakriya M, Ezponda T, Hildeman DA, Wang CR, Schumacker PT, Licht JD, Perlman H, Bryce PJ, Chandel NS (2013) Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling. Immunity 38(2):225–236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Ogura M, Inoue T, Yamaki J, Homma MK, Kurosaki T, Homma Y (2017) Mitochondrial reactive oxygen species suppress humoral immune response through reduction of CD19 expression in B cells in mice. Eur J Immunol 47(2):406–418

    Article  CAS  PubMed  Google Scholar 

  52. Wheeler ML, Defranco AL (2012) Prolonged production of reactive oxygen species in response to B cell receptor stimulation promotes B cell activation and proliferation. J Immunol 189(9):4405–4416

    Article  CAS  PubMed  Google Scholar 

  53. Victora GD, Nussenzweig MC (2022) Germinal centers. Annu Rev Immunol 40:413–442

    Article  CAS  PubMed  Google Scholar 

  54. Wei X, Niu X (2023) T follicular helper cells in autoimmune diseases. J Autoimmun 134:102976

    Article  CAS  PubMed  Google Scholar 

  55. Stockwell BR, Friedmann Angeli JP, Bayir H, Bush AI, Conrad M, Dixon SJ, Fulda S, Gascón S, Hatzios SK, Kagan VE, Noel K, Jiang X, Linkermann A, Murphy ME, Overholtzer M, Oyagi A, Pagnussat GC, Park J, Ran Q, Rosenfeld CS, Salnikow K, Tang D, Torti FM, Torti SV, Toyokuni S, Woerpel KA, Zhang DD (2017) Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell 171(2):273–285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Yao Y, Chen Z, Zhang H, Chen C, Zeng M, Yunis J, Wei Y, Wan Y, Wang N, Zhou M, Qiu C, Zeng Q, Ong HS, Wang H, Makota FV, Yang Y, Yang Z, Wang N, Deng J, Shen C, Xia Y, Yuan L, Lian Z, Deng Y, Guo C, Huang A, Zhou P, Shi H, Zhang W, Yi H, Li D, Xia M, Fu J, Wu N, De Haan JB, Shen N, Zhang W, Liu Z, Yu D (2021) Selenium-GPX4 axis protects follicular helper T cells from ferroptosis. Nat Immunol 22(9):1127–1139

    Article  CAS  PubMed  Google Scholar 

  57. He X, Lin Y, Lian S, Sun D, Guo D, Wang J, Wu R (2020) Selenium deficiency in chickens induces intestinal mucosal injury by affecting the mucosa morphology, SIgA secretion, and GSH-Px activity. Biol Trace Elem Res 197(2):660–666

    Article  CAS  PubMed  Google Scholar 

  58. Liu Z, Qu Y, Wang J, Wu R (2016) Selenium deficiency attenuates chicken duodenal mucosal immunity via activation of the NF-κb signaling pathway. Biol Trace Elem Res 172(2):465–473

    Article  CAS  PubMed  Google Scholar 

  59. Galdeano CM, Perdigón G (2006) The probiotic bacterium Lactobacillus casei induces activation of the gut mucosal immune system through innate immunity. Clin Vaccine Immunol 13(2):219–226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Caggianiello G, Kleerebezem M, Spano G (2016) Exopolysaccharides produced by lactic acid bacteria: from health-promoting benefits to stress tolerance mechanisms. Appl Microbiol Biotechnol 100(9):3877–3886

    Article  CAS  PubMed  Google Scholar 

  61. Ivanov D, Emonet C, Foata F, Affolter M, Delley M, Fisseha M, Blum-Sperisen S, Kochhar S, Arigoni F (2006) A serpin from the gut bacterium Bifidobacterium longum inhibits eukaryotic elastase-like serine proteases. J Biol Chem 281(25):17246–17252

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We acknowledge the support provided by Northeast Agricultural University, the State Key Laboratory of Veterinary Biotechnology Foundation, and the National Natural Science Foundation of China.

Funding

The authors state that they have received funding for this article’s research, writing, and/or publishing. The National Natural Science Foundation of China provided funding for this study (Grant No. 31672532) and the SIPT Project of Northeast Agricultural University.

Author information

Authors and Affiliations

Authors

Contributions

J.G. and F.W.: conceived and designed the experiments. Z.Z., X.D., Y.L., and Z.Y.:performed the experiments. W.S., R.L.: analyzed the data. N.L., J.W, J.W., and Y.M.:contributed reagents, materials, and analysis tools. J.G., F.W., Z.Z., and X.D.: wrote the paper. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Fang Wang or Junwei Ge.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, Z., De, X., Sun, W. et al. Biogenic Selenium Nanoparticles Synthesized by L. brevis 23017 Enhance Aluminum Adjuvanticity and Make Up for its Disadvantage in Mice. Biol Trace Elem Res (2024). https://doi.org/10.1007/s12011-023-04042-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12011-023-04042-y

Keywords

Navigation