Abstract
Silica-based materials have attracted considerable interest as vaccine adjuvants due to their ability to potentiate immune responses. In this study, we evaluated the immunogenicity and protective efficacy of heteromorphous mesoporous silicon microparticles (MSMPs) as an adjuvant in the context of SARS-CoV-2 vaccination. MSMPs conjugated with the S1 subunit of the spike protein (MSMPs-S1) elicited a robust and sustained humoral immune response in BALB/c mice, comparable to that induced by aluminum-based adjuvants. Following a booster dose, MSMPs-S1 significantly increased IgG2a titers and neutralizing antibody levels, surpassing those observed with Al(OH)₃-based formulations. In addition, MSMPs-S1 enhanced cellular immunity, as reflected by higher IFN-γ production in T cells relative to the aluminum-adjuvanted group. In k18-hACE2 transgenic mice, vaccination with MSMPs-S1 conferred protection against a lethal SARS-CoV-2 challenge, resulting in marked reductions in viral loads in both lung and brain tissues. In vitro, stimulation of human peripheral blood mononuclear cells (PBMCs) with MSMPs-S1 increased IFN-γ production in T cells, particularly in the presence of dendritic cells. Collectively, these findings support the potential of MSMPs as an effective adjuvant capable of promoting both humoral and cellular immunity, with relevance for the development of vaccines targeting emerging viral pathogens.
Data availability
The datasets generated and/or analysed during the current study are available from the corresponding author upon reasonable request.
References
Verma, S. K. et al. New-age vaccine adjuvants, their development, and future perspective. Front. Immunol. 14, 1043109. https://doi.org/10.3389/fimmu.2023.1043109 (2023).
Pulendran, B., Arunachalam, P. S. & O’Hagan, D. T. Emerging concepts in the science of vaccine adjuvants., Nat. Rev. Drug Discov., 20 (6), 454–475 (2021). https://doi.org/10.1038/s41573-021-00163-y
Audran, R. et al. Mar., Encapsulation of peptides in biodegradable microspheres prolongs their MHC class-I presentation by dendritic cells and macrophages in vitro., Vaccine, 21(11–12), 1250–1255 (2003). https://doi.org/10.1016/s0264-410x(02)00521-2
Langer, R., Cleland, J. L. & Hanes, J. New advances in microsphere-based single-dose vaccines., Adv. Drug Deliv. Rev., 28(1), 97–119 (1997). https://doi.org/10.1016/s0169-409x(97)00053-7
Jiménez-Periáñez, A. et al. Mesoporous silicon microparticles enhance MHC class i cross-antigen presentation by human dendritic cells. Clin. Dev. Immunol. 2013 https://doi.org/10.1155/2013/362163 (2013).
Fiolet, T., Kherabi, Y., MacDonald, C. J., Ghosn, J. & Peiffer-Smadja, N. Comparing COVID-19 vaccines for their characteristics, efficacy and effectiveness against SARS-CoV-2 and variants of concern: a narrative review., Clin. Microbiol. Infect. Off. Publ. Eur. Soc. Clin. Microbiol. Infect. Dis., 28(2), 202–221 (2022). https://doi.org/10.1016/j.cmi.2021.10.005
Doria-Rose, N. et al. Jun., Antibody Persistence through 6 Months after the Second Dose of mRNA-1273 Vaccine for Covid-19., N. Engl. J. Med., 384(23), 2259–2261 (2021). (United States) https://doi.org/10.1056/NEJMc2103916
Barouch, D. H. et al. Sep., Durable Humoral and Cellular Immune Responses 8 Months after Ad26.COV2.S Vaccination., N. Engl. J. Med., 385(10), 951–953 (2021). (United States) https://doi.org/10.1056/NEJMc2108829
Yang, L. T. et al. Aug., Long-lived effector/central memory T-cell responses to severe acute respiratory syndrome coronavirus (SARS-CoV) S antigen in recovered SARS patients., Clin. Immunol., 120(2), 171–178 (2006). https://doi.org/10.1016/j.clim.2006.05.002
Enjuanes, L. et al. Molecular basis of coronavirus virulence and vaccine development. Adv. Virus Res. 96, 245–286. https://doi.org/10.1016/bs.aivir.2016.08.003 (2016).
Channappanavar, R., Zhao, J. & Perlman, S. T cell-mediated immune response to respiratory coronaviruses. Immunol. Res. 59, 1–3. https://doi.org/10.1007/s12026-014-8534-z (2014).
López-Gomez, A., Real-Arévalo, I., Martín-Palma, R., Martínez-Naves, E. & Del Moral, M. G. Manufacture of mesoporous silicon microparticles (MSMPs) as adjuvants for vaccine delivery. Methods Mol. Biol. 2673, 123–130. https://doi.org/10.1007/978-1-0716-3239-0_8 (2023).
Alcolea, P. J. et al. Non-replicative antibiotic resistance-free DNA vaccine encoding S and N proteins induces full protection in mice against SARS-CoV-2. Front. Immunol. 13, 1023255. https://doi.org/10.3389/fimmu.2022.1023255 (2022).
Navarro-Tovar, G., Rocha-García, D., Wong-Arce, A., Palestino, G. & Rosales-Mendoza, S. Mesoporous silicon particles favor the induction of long-lived humoral responses in mice to a peptide-based vaccine. Mater. (Basel). 11 (7). https://doi.org/10.3390/ma11071083 (2018).
Castillo, R. R. et al. Advances in mesoporous silica nanoparticles for targeted stimuli-responsive drug delivery: an update., Expert Opin. Drug Deliv., 16(4), 415–439 (2019). https://doi.org/10.1080/17425247.2019.1598375
Abbaraju, P. L. et al. Asymmetric Silica Nanoparticles with Tunable Head-Tail Structures Enhance Hemocompatibility and Maturation of Immune Cells. J. Am. Chem. Soc. 139, 6321–6328. https://doi.org/10.1021/jacs.6b12622 (2017).
Yan, J. et al. Porous silicon and silica carriers for delivery of peptide therapeutics., Drug Deliv. Transl. Res., 14(12), 3549–3567 (2024). https://doi.org/10.1007/s13346-024-01609-7
Abbaraju, P. L. et al. Asymmetric mesoporous silica nanoparticles as potent and safe immunoadjuvants provoke high immune responses., Chem. Commun. (Camb)., 54(16), 2020–2023 (2018). https://doi.org/10.1039/c8cc00327k
Janeway, C. A. J. Approaching the asymptote? Evolution and revolution in immunology., Cold Spring Harb. Symp. Quant. Biol., 54(1), 1–13 (1989). https://doi.org/10.1101/sqb.1989.054.01.003
Liu, Z. et al. Size effect of mesoporous silica nanoparticles on regulating the immune effect of oral influenza split vaccine. Colloids Surf. B Biointerfaces 238, 113920. https://doi.org/10.1016/j.colsurfb.2024.113920 (2024).
García-Pérez, J. et al. Immunogenic dynamics and SARS-CoV-2 variant neutralisation of the heterologous ChAdOx1-S/BNT162b2 vaccination: Secondary analysis of the randomised CombiVacS study. EClinicalMedicine 50, 101529. https://doi.org/10.1016/j.eclinm.2022.101529 (2022).
Lin, Q., Zhu, L., Ni, Z., Meng, H. & You, L. Duration of serum neutralizing antibodies for SARS-CoV-2: Lessons from SARS-CoV infection., Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi, 53 (5), 821–822 (2020). (England) https://doi.org/10.1016/j.jmii.2020.03.015
Flaxman, A. et al. Sep., Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 in the UK: a substudy of two randomised controlled trials (COV001 and COV002)., Lancet (London, England), 398 (10304), 981–990 (2021). https://doi.org/10.1016/S0140-6736(21)01699-8
Nazeri, S., Zakeri, S., Mehrizi, A. A., Sardari, S. & Djadid, N. D. Measuring of IgG2c isotype instead of IgG2a in immunized C57BL/6 mice with plasmodium Vivax TRAP as a subunit vaccine candidate in order to correct interpretation of Th1 versus Th2 immune response. Exp. Parasitol. 216 https://doi.org/10.1016/J.EXPPARA.2020.107944 (Sep. 2020).
Adam, A. et al. Nov., A modified porous silicon microparticle potentiates protective systemic and mucosal immunity for SARS-CoV-2 subunit vaccine., Transl. Res., 249, 13–27 (2022). https://doi.org/10.1016/j.trsl.2022.06.004
Barnes, C. O. et al. SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies. Nature 588(7839), 682. https://doi.org/10.1038/S41586-020-2852-1 (2020).
Li, H. et al. The abundant distribution and duplication of SARS-CoV-2 in the cerebrum and lungs promote a high mortality rate in Transgenic hACE2-C57 mice. Int. J. Mol. Sci. 25 (2). https://doi.org/10.3390/ijms25020997 (2024).
Starr, T. N. et al. Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding. Cell 182(5), 1295–1310. https://doi.org/10.1016/J.CELL.2020.08.012 (2020) (.e20).
Liu, H. et al. The basis of a more contagious 501Y.V1 variant of SARS-CoV-2. Cell. Res. 31(6), 720–722. https://doi.org/10.1038/S41422-021-00496-8 (2021).
García-Arriaza, J. et al. Mar., COVID-19 Vaccine Candidates Based on Modified Vaccinia Virus Ankara Expressing the SARS-CoV-2 Spike Protein Induce Robust T- and B-Cell Immune Responses and Full Efficacy in Mice, J. Virol., 95(7), (2021). https://doi.org/10.1128/JVI.02260-20
He, P., Zou, Y. & Hu, Z. Advances in aluminum hydroxide-based adjuvant research and its mechanism. Hum. Vaccin Immunother. 11 (2), 477. https://doi.org/10.1080/21645515.2014.1004026 (2015).
Hudu, S. A., Shinkafi, S. H. & Umar, S. An overview of Recombinant vaccine technology, adjuvants and vaccine delivery methods. Int. J. Pharm. Pharm. Sci. 8 (11), 19–24. https://doi.org/10.22159/ijpps.2016v8i11.14311 (2016).
Funding
This work was supported by grants from Comunidad de Madrid (COV20/01101-CM and REACT-UE, ANTICIPA-CM Ref. PR38/21–24) to E.M.N and M.G.M and from Spanish Ministry of Science and Innovation (RETOS PID2022-1366620B-100) to M.G.M.
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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by A.L-G., I.R-A., E.M-H., J.A.C., D.L-F., P. N-A., B R-P., B. A-P., B. M-A. and I. J. The first draft of the manuscript was written by M. G. M., E.M.N., and A. L-G. N.S., A. M-del-P. and R. J. M-P. commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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López-Gómez, A., Real-Arévalo, I., Mayol-Hornero, E. et al. Mesoporous silicon microparticles enhance antiviral immunity and memory responses against SARS-CoV-2. Sci Rep (2026). https://doi.org/10.1038/s41598-026-38583-8
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DOI: https://doi.org/10.1038/s41598-026-38583-8