Nanomaterial for Adjuvants Vaccine: Practical Applications and Prospects

Vy Anh Tran(1*), Vien Vo(2), Vinh Quang Dang(3), Giang Ngoc Linh Vo(4), Ta Ngoc Don(5), Van Dat Doan(6), Van Thuan Le(7)

(1) Institute of Applied Technology and Sustainable Development, Nguyen Tat Thanh University, Ho Chi Minh City 700000, Vietnam; Faculty of Environmental and Food Engineering, Nguyen Tat Thanh University, Ho Chi Minh City 700000, Vietnam
(2) Faculty of Natural Sciences, Quy Nhon University, 170 An Duong Vuong, Quy Nhon, Binh Dinh 55000, Vietnam
(3) Faculty of Materials Science and Technology, University of Science, 227 Nguyen Van Cu Street, District 5, Ho Chi Minh City 700000, Vietnam; Vietnam National University, Ho Chi Minh City 700000, Vietnam
(4) Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 700000, Vietnam
(5) Ministry of Education and Training, Ha Noi City 570000, Vietnam
(6) The Faculty of Chemical Engineering, Industrial University of Ho Chi Minh City, Ho Chi Minh City 700000, Vietnam
(7) Center for Advanced Chemistry, Institute of Research and Development, Duy Tan University, 03 Quang Trung, Da Nang 550000, Vietnam; Faculty of Natural Sciences, Duy Tan University, 03 Quang Trung, Da Nang 550000, Vietnam
(*) Corresponding Author


Vaccines contain adjuvants to strengthen the immune responses of the receiver against pathogen infection or malignancy. A new generation of adjuvants is being developed to give more robust antigen-specific responses, specific types of immune responses, and a high margin of safety. By changing the physical and chemical properties of nanomaterials, it is possible to make antigen-delivery systems with high bioavailability, controlled and sustained release patterns, and the ability to target and image. Nanomaterials can modulate the immune system so that cellular and humoral immune responses more closely resemble those desired. The use of nanoparticles as adjuvants is believed to significantly improve the immunological outcomes of vaccination because of the combination of their immunomodulatory and delivery effects. In this review, we discuss the recent developments in new adjuvants using nanomaterials. Based on three main vaccines, the subunit, DNA, and RNA vaccines, the possible ways that nanomaterials change the immune responses caused by vaccines, such as a charge on the surface or a change to the surface, and how they affect the immunological results have been studied. This study aims to provide succinct information on the use of nanomaterials for COVID-19 vaccines and possible new applications.


nanomaterials; adjuvants vaccine; subunit vaccine; DNA vaccine; RNA vaccine; Covid-19 vaccine

Full Text:

Full Text PDF


[1] Rana, M.M., 2021, Polymer-based nano-therapies to combat COVID-19 related respiratory injury: progress, prospects, and challenges, J. Biomater. Sci., Polym. Ed., 32 (9), 1219–1249.

[2] Nayak, S.K., 2020, Current prospects and challenges in fish vaccine development in India with special reference to Aeromonas hydrophila vaccine, Fish Shellfish Immunol., 100, 283–299.

[3] Mba, I.E., Sharndama, H.C., Anyaegbunam, Z.K.G., Anekpo, C.C., Amadi, B.C., Morumda, D., Doowuese, Y., Ihezuo, U.J., Chukwukelu, J.U., and Okeke, O.P., 2023, Vaccine development for bacterial pathogens: Advances, challenges and prospects, Trop. Med. Int. Health, 28 (4), 275–299.

[4] Ou, B., Yang, Y., Lv, H., Lin, X., and Zhang, M., 2023, Current progress and challenges in the study of adjuvants for oral vaccines, BioDrugs, 37 (2), 143–180.

[5] Anh Tran, V., Nhu Quynh, L.T., Thi Vo, T.T., Nguyen, P.A., Don, T.N., Vasseghian, Y., Phan, H., and Lee, S.W., 2022, Experimental and computational investigation of a green Knoevenagel condensation catalyzed by zeolitic imidazolate framework-8, Environ. Res., 204, 112364.

[6] Tran, V.A., Kadam, A.N., and Lee, S.W., 2020, Adsorption-assisted photocatalytic degradation of methyl orange dye by zeolite-imidazole-framework-derived nanoparticles, J. Alloys Compd., 835, 155414.

[7] Tran, V.A., Vo, G.V., Tan, M.A., Park, J.S., An, S.S.A., and Lee, S.W., 2022, Dual stimuli-responsive multifunctional silicon nanocarriers for specifically targeting mitochondria in human cancer cells, Pharmaceutics, 14 (4), 858.

[8] Tran, V.A., Do, H.H., Le, V.T., Vasseghian, Y., Vo, V., Ahn, S.H., Kim, S.Y., and Lee, S.W., 2022, Metal-organic-framework-derived metals and metal compounds as electrocatalysts for oxygen evolution reaction: A review, Int. J. Hydrogen Energy, 47 (45), 19590–19608.

[9] Tran, V.A., Vo, G.N.L., Vo, T.T.T., Doan, V.D., Vo, V., and Le, V.T., 2023, Recent applications and prospects of nanowire-based biosensors, Processes, 11 (6), 1739.

[10] Tran, V.A., Doan, V.D., Le, V.T., Nguyen, T.Q., Don, T.N., Vien, V., Luan, N.T., and Vo, G.N.L., 2023, Metal–organic frameworks-derived material for electrochemical biosensors: Recent applications and prospects, Ind. Eng. Chem. Res., 62 (11), 4738–4753.

[11] Tran, V.A., Tran, N.T., Doan, V.D., Nguyen, T.Q., Pham Thi, H.H., and Vo, G.N.L., 2023, Application prospects of MXenes materials modifications for sensors, Micromachines, 14 (2), 247.

[12] Etefia, E., and Inyang-Etoh, P., 2023, Malaria vaccine development: Challenges and prospects, Med. Pharm. J., 2 (1), 28–42.

[13] Alexander-Miller, M.A., 2020, Challenges for the newborn following influenza virus infection and prospects for an effective vaccine, Front Immunol., 11, 568651.

[14] Batista-Duharte, A., Pera, A., Aliño, S.F., and Solana, R., 2021, Regulatory T cells and vaccine effectiveness in older adults. Challenges and prospects, Int. Immunopharmacol., 96, 107761.

[15] Zhu, M., Wang, R., and Nie, G., 2014, Applications of nanomaterials as vaccine adjuvants, Hum. Vaccines Immunother., 10 (9), 2761–2774.

[16] Shen, Y., Hao, T., Ou, S., Hu, C., and Chen, L., 2018, Applications and perspectives of nanomaterials in novel vaccine development, MedChemComm, 9 (2), 226–238.

[17] Shin, M.D., Shukla, S., Chung, Y.H., Beiss, V., Chan, S.K., Ortega-Rivera, O.A., Wirth, D.M., Chen, A., Sack, M., Pokorski, J.K., and Steinmetz, N.F., 2020, COVID-19 vaccine development and a potential nanomaterial path forward, Nat. Nanotechnol., 15 (8), 646–655.

[18] Tran, V.A., and Lee, S.W., 2021, pH-triggered degradation and release of doxorubicin from zeolitic imidazolate framework-8 (ZIF8) decorated with polyacrylic acid, RSC Adv., 11 (16), 9222–9234.

[19] Tran, V.A., Vo, V.G., Shim, K., Lee, S.W., and An, S.S.A., 2020, Multimodal mesoporous silica nanocarriers for dual stimuli-responsive drug release and excellent photothermal ablation of cancer cells, Int. J. Nanomed., 15, 7667–7685.

[20] Tran, V.A., and Lee, S.W., 2018, A prominent anchoring effect on the kinetic control of drug release from mesoporous silica nanoparticles (MSNs), J. Colloid Interface Sci., 510, 345–356.

[21] Tran, A.V., Shim, K., Vo Thi, T.T., Kook, J.K., An, S.S.A., and Lee, S.W., 2018, Targeted and controlled drug delivery by multifunctional mesoporous silica nanoparticles with internal fluorescent conjugates and external polydopamine and graphene oxide layers, Acta Biomater., 74, 397–413.

[22] Pulendran, B., Arunachalam, P.S., and O’Hagan, D.T., 2021, Emerging concepts in the science of vaccine adjuvants, Nat. Rev. Drug Discovery, 20 (6), 454–475.

[23] Fan, J., Jin, S., Gilmartin, L., Toth, I., Hussein, W.M., and Stephenson, R.J., 2022, Advances in infectious disease vaccine adjuvants, Vaccines, 10 (7), 1120.

[24] Mao, L., Chen, Z., Wang, Y., and Chen, C., 2021, Design and application of nanoparticles as vaccine adjuvants against human corona virus infection, J. Inorg. Biochem., 219, 111454.

[25] Zhao, T., Cai, Y., Jiang, Y., He, X., Wei, Y., Yu, Y., and Tian, X., 2023, Vaccine adjuvants: Mechanisms and platforms, Signal Transduction Targeted Ther., 8 (1), 283.

[26] Chatzikleanthous, D., O’Hagan, D.T., and Adamo, R., 2021, Lipid-based nanoparticles for delivery of vaccine adjuvants and antigens: Toward multicomponent vaccines, Mol. Pharmaceutics, 18 (8), 2867–2888.

[27] Park, H., Ma, G.J., Yoon, B.K., Cho, N.J., and Jackman, J.A., 2021, Comparing protein adsorption onto alumina and silica nanomaterial surfaces: clues for vaccine adjuvant development, Langmuir, 37 (3), 1306–1314.

[28] Fries, C.N., Curvino, E.J., Chen, J.L., Permar, S.R., Fouda, G.G., and Collier, J.H., 2021, Advances in nanomaterial vaccine strategies to address infectious diseases impacting global health, Nat. Nanotechnol., 16 (4), 1–14.

[29] Liang, J., and Zhao, X., 2021, Nanomaterial-based delivery vehicles for therapeutic cancer vaccine development, Cancer Biol. Med., 18 (2), 352–371.

[30] Sun, B., Li, M., Yao, Z., Yu, G., and Ma, Y., 2023, “Advances in Vaccine Adjuvants: Nanomaterials and Small Molecules” in Handbook of Experimental Pharmacology, Springer Berlin Heidelberg, Berlin, Heidelberg, 1–20.

[31] Vartak, A., and Sucheck, S.J., 2016, Recent advances in subunit vaccine carriers, Vaccines, 4 (2), 12.

[32] Luzuriaga, M.A., Shahrivarkevishahi, A., Herbert, F.C., Wijesundara, Y.H., and Gassensmith, J.J., 2021, Biomaterials and nanomaterials for sustained release vaccine delivery, WIREs Nanomed. Nanobiotechnol., 13 (6), e1735.

[33] Zhao, L., Jin, W., Cruz, J.G., Marasini, N., Khalil, Z.G., Capon, R.J., Hussein, W.M., Skwarczynski, M., and Toth, I., 2020, Development of polyelectrolyte complexes for the delivery of peptide-based subunit vaccines against group A streptococcus, Nanomaterials, 10 (5), 823.

[34] Yavuz, E., Walters, A.A., Chudasama, B.V., Han, S., Qin, Y., and Al-Jamal, K.T., 2023, Investigating the potential of cuboidal nanometals as protein subunit vaccine carriers in vivo, Adv. Mater. Interfaces, 10 (29), 2202511.

[35] Mekonnen, D., Mengist, H.M., and Jin, T., 2022, SARS-CoV-2 subunit vaccine adjuvants and their signaling pathways, Expert Rev. Vaccines, 21 (1), 69–81.

[36] Zhang, T., Zhang, L., Wu, X., Xu, H., Hao, P., Huang, W., Zhang, Y., and Zan, X., 2020, Hexahistidine–metal assemblies: A facile and effective codelivery system of subunit vaccines for potent humoral and cellular immune responses, Mol. Pharmaceutics, 17 (7), 2487–2498.

[37] Khalaj-Hedayati, A., Chua, C.L.L., Smooker, P., and Lee, K.W., 2020, Nanoparticles in influenza subunit vaccine development: Immunogenicity enhancement, Influenza Other Respir. Viruses, 14 (1), 92–101.

[38] Chen, H., Liu, H., Liu, L., and Chen, Y., 2022, Fabrication of subunit nanovaccines by physical interaction, Sci. China: Technol. Sci., 65, (5), 989–999.

[39] Park, J., and Champion, J.A., 2023, Effect of antigen structure in subunit vaccine nanoparticles on humoral immune responses, ACS Biomater. Sci. Eng., 9 (3), 1296–1306

[40] Lam, J.H., Khan, A.K., Cornell, T.A., Chia, T.W., Dress, R.J., Yeow, W.W.W., Mohd-Ismail, N.K., Venkataraman, S., Ng, K.T., Tan, Y.J., Anderson, D.E., Ginhoux, F., and Nallani, M., 2021, Polymersomes as stable nanocarriers for a highly immunogenic and durable SARS-CoV-2 spike protein subunit vaccine, ACS Nano, 15 (10), 15754–15770.

[41] Li, X., He, X., He, D., Liu, Y., Chen, K., and Yin, P., 2021, A polymeric co-assembly of subunit vaccine with polyoxometalates induces enhanced immune responses, Nano Res., 15 (5), 4175–4180.

[42] Quach, Q.H., Ang, S.K., Chu, J.H.J., and Kah, J.C.Y., 2018, Size-dependent neutralizing activity of gold nanoparticle-based subunit vaccine against dengue virus, Acta Biomater., 78, 224–235.

[43] Buschmann, M.D., Carrasco, M.J., Alishetty, S., Paige, M., Alameh, M.G., and Weissman, D., 2021, Nanomaterial delivery systems for mRNA vaccines, Vaccines, 9 (1), 65.

[44] Karam, M., and Daoud, G., 2022, mRNA vaccines: Past, present, future, Asian J. Pharm. Sci., 17 (4), 491–522.

[45] McKay, P.F., Hu, K., Blakney, A.K., Samnuan, K., Brown, J.C., Penn, R., Zhou, J., Bouton, C.R., Rogers, P., Polra, K., Lin, P.J.C., Barbosa, C., Tam, Y.K., Barclay, W.S., and Shattock, R.J., 2020, Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice, Nat. Commun., 11 (1), 3523.

[46] Hassett, K.J., Higgins, J., Woods, A., Levy, B., Xia, Y., Hsiao, C.J., Acosta, E., Almarsson, Ö., Moore, M.J., and Brito, L.A., 2021, Impact of lipid nanoparticle size on mRNA vaccine immunogenicity, J. Controlled Release, 335, 237–246.

[47] Ho, W., Gao, M., Li, F., Li, Z., Zhang, X.Q., and Xu, X., 2021, Next-generation vaccines: Nanoparticle-mediated DNA and mRNA delivery, Adv. Healthcare Mater., 10 (8), 2001812.

[48] Tenchov, R., Bird, R., Curtze, A.E., and Zhou, Q., 2021, Lipid nanoparticles─From liposomes to mRNA vaccine delivery, a landscape of research diversity and advancement, ACS Nano, 15 (11), 16982–17015.

[49] Wilson, B., and Geetha, K.M., 2022, Lipid nanoparticles in the development of mRNA vaccines for COVID-19, J. Drug Deliv. Sci. Technol., 74, 103553.

[50] Yin, Y., Li, X., Ma, H., Zhang, J., Yu, D., Zhao, R., Yu, S., Nie, G., and Wang, H., 2021, In situ transforming RNA nanovaccines from polyethylenimine functionalized graphene oxide hydrogel for durable cancer immunotherapy, Nano Lett., 21 (5), 2224–2231.

[51] Zheng, W., Han, B., E, S., Sun, Y., Li, X., Cai, Y., and Zhang, Y. 2020, Highly-sensitive and reflective glucose sensor based on optical fiber surface plasmon resonance, Microchem. J., 157, 105010.

[52] Dong, C., Wang, Y., Gonzalez, G.X., Ma, Y., Song, Y., Wang, S., Kang, S.M., Compans, R.W., and Wang, B.Z., 2021, Intranasal vaccination with influenza HA/GO-PEI nanoparticles provides immune protection against homo- and heterologous strains, Proc. Natl. Acad. Sci. U. S. A., 118 (19), e2024998118.

[53] Luo, X., Zeng, X., Gong, L., Ye, Y., Sun, C., Chen, T., Zhang, Z., Tao, Y., Zeng, H., Zou, Q., Yang, Y., Li, J., and Sun, H., 2022, Nanomaterials in tuberculosis DNA vaccine delivery: Historical perspective and current landscape, Drug Delivery, 29 (1), 2912–2924.

[54] Sun, B., Zhao, X., Gu, W., Cao, P., Movahedi, F., Wu, Y., Xu, Z.P., and Gu, W., 2021, ATP stabilised and sensitised calcium phosphate nanoparticles as effective adjuvants for a DNA vaccine against cancer, J. Mater. Chem. B, 9 (36), 7435–7446.

[55] Zhao, K., Sun, B., Shi, C., Sun, Y., Jin, Z., and Hu, G., 2021, Intranasal immunization with O-2′-Hydroxypropyl trimethyl ammonium chloride chitosan nanoparticles loaded with Newcastle disease virus DNA vaccine enhances mucosal immune response in chickens, J. Nanobiotechnol., 19 (1), 240.

[56] Tian, R., Shang, Y., Wang, Y., Jiang, Q., and Ding, B., 2023, DNA nanomaterials-based platforms for cancer immunotherapy, Small Methods, 7 (5), 2201518.

[57] Zhao, K., Rong, G., Teng, Q., Li, X., Lan, H., Yu, L., Yu, S., Jin, Z., Chen, G., and Li, Z., 2020, Dendrigraft poly-L-lysines delivery of DNA vaccine effectively enhances the immunogenic responses against H9N2 avian influenza virus infection in chickens, Nanomed.: Nanotechnol. Biol. Med., 27, 102209.

[58] He, L., Mu, J., Gang, O., and Chen, X., 2021, Rationally programming nanomaterials with DNA for biomedical applications, Adv. Sci., 8 (8), 2003775.

[59] Zhao, Z., Ma, X., Zhang, R., Hu, F., Zhang, T., Liu, Y., Han, M.H., You, F., Yang, Y., and Zheng, W., 2021, A novel liposome-polymer hybrid nanoparticles delivering a multi-epitope self-replication DNA vaccine and its preliminary immune evaluation in experimental animals, Nanomed.: Nanotechnol. Biol. Med., 35, 102338.

[60] Mucker, E.M., Karmali, P.P., Vega, J., Kwilas, S.A., Wu, H., Joselyn, M., Ballantyne, J., Sampey, D., Mukthavaram, R., Sullivan, E., Chivukula, P., and Hooper, J.W., 2020, Lipid nanoparticle formulation increases efficiency of DNA-vectored vaccines/immunoprophylaxis in animals including transchromosomic bovines, Sci. Rep., 10 (1), 8764.

[61] Song, H., Yang, Y., Tang, J., Gu, Z., Wang, Y., Zhang, M., and Yu, C., 2020, DNA vaccine mediated by rambutan-like mesoporous silica nanoparticles, Adv. Ther., 3 (1), 1900154.

[62] Lu, Y., Wu, F., Duan, W., Mu, X., Fang, S., Lu, N., Zhou, X., and Kong, W., 2020, Engineering a “PEG-g-PEI/DNA nanoparticle-in- PLGA microsphere” hybrid controlled release system to enhance immunogenicity of DNA vaccine, Mater. Sci. Eng., C, 106, 110294.

[63] Rauf, A., Abu-Izneid, T., Khalil, A.A., Hafeez, N., Olatunde, A., Rahman, M.M., Semwal, P., Al-Awthan, Y.S., Bahattab, O.S., Khan, I.N., Khan, M.A., and Sharma, R., 2022, Nanoparticles in clinical trials of COVID-19: An update, Int. J. Surg., 104, 106818.

[64] Yasamineh, S., Kalajahi, H.G., Yasamineh, P., Yazdani, Y., Gholizadeh, O., Tabatabaie, R., Afkhami, H., Davodabadi, F., Farkhad, A.K., Pahlevan, D., Firouzi-Amandi, A., Nejati-Koshki, K., and Dadashpour, M., 2022, An overview on nanoparticle-based strategies to fight viral infections with a focus on COVID-19, J. Nanobiotechnol., 20 (1), 440.

[65] Han, H.J., Nwagwu, C., Anyim, O., Ekweremadu, C., and Kim, S., 2021, COVID-19 and cancer: From basic mechanisms to vaccine development using nanotechnology, Int. Immunopharmacol., 90, 107247.

[66] Xu, C., Lei, C., Hosseinpour, S., Ivanovski, S., Walsh, L.J., and Khademhosseini, A., 2022, Nanotechnology for the management of COVID-19 during the pandemic and in the post-pandemic era, Natl. Sci. Rev., 9 (10), nwac124.

[67] Patel, U., Rathnayake, K., Hunt, E.C., and Singh, N., 2022, Role of nanomaterials in COVID-19 prevention, diagnostics, therapeutics, and vaccine development, J. Nanotheranostics, 3 (4), 151–176.

[68] Ayan, S., Aranci-Ciftci, K., Ciftci, F., and Ustundag, C.B., 2023, Nanotechnology and COVID-19: Prevention, diagnosis, vaccine, and treatment strategies, Front. Mater., 9, 1059184.

[69] Wang, Z., Cui, K., Costabel, U., and Zhang, X., 2022, Nanotechnology-facilitated vaccine development during the coronavirus disease 2019 (COVID-19) pandemic, Exploration, 2 (5), 20210082.

[70] Chung, Y.H., Beiss, V., Fiering, S.N., and Steinmetz, N.F., 2020, COVID-19 vaccine frontrunners and their nanotechnology design, ACS Nano, 14 (10), 12522–12537.

[71] Ho, H.M., Huang, C.Y., Cheng, Y.J., Shen, K.Y., Tzeng, T.T., Liu, S.J., Chen, H.W., Huang, C.H., and Huang, M.H., 2021, Assessment of adjuvantation strategy of lipid squalene nanoparticles for enhancing the immunogenicity of a SARS-CoV-2 spike subunit protein against COVID-19, Int. J. Pharm., 607, 121024.

[72] Xie, X., Song, T., Feng, Y., Zhang, H., Yang, G., Wu, C., You, F., Liu, Y., and Yang, H., 2022, Nanotechnology-based multifunctional vaccines for cancer immunotherapy, Chem. Eng. J., 437, 135505.


Article Metrics

Abstract views : 793 | views : 450

Copyright (c) 2023 Indonesian Journal of Chemistry

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.


Indonesian Journal of Chemistry (ISSN 1411-9420 /e-ISSN 2460-1578) - Chemistry Department, Universitas Gadjah Mada, Indonesia.

Analytics View The Statistics of Indones. J. Chem.