Protein A-antigen conjugates enhance production of specific antibodies following intranasal administration
- Authors: Volosnikova E.A.1, Volkova N.V.1, Gayvoronskiy S.I.1, Simakova O.V.1, Esina T.I.1, Rar A.A.1, Shcherbakov D.N.1
-
Affiliations:
- State Research Center of Virology and Biotechnology “Vector”
- Issue: Vol 28, No 3 (2025)
- Pages: 567-572
- Section: SHORT COMMUNICATIONS
- URL: https://journals.rcsi.science/1028-7221/article/view/319902
- DOI: https://doi.org/10.46235/1028-7221-17148-PAA
- ID: 319902
Cite item
Full Text
Abstract
The objective of our work was to study immunogenic properties of protein A conjugates with the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (B.1.617.2, Delta variant) and their ability to induce a specific humoral immune response following intranasal administration. Recombinant RBD (SARS-CoV-2, Delta variant) conjugates with Staphylococcus aureus protein A were prepared using EDC or Sulfo-SMCC (1:1 molar ratio) followed by gel filtration purification. Immunization procedure was performed in 80 six-week-old Balb/c mice, divided into groups of 10 animals. Experimental groups received intranasal administration of 20 µL conjugate (50 µg RBD) twice at a 14-day interval, while control groups received intramuscular RBD or saline. Blood was collected 10 days after boosting. Specific IgG titers were determined by ELISA using RBD as the antigen. Statistical significance was assessed using the Mann–Whitney U test (GraphPad Prism 8.0, p < 0.05). Intranasal administration of RBD-protein A conjugates (Con-S and Con-E) induced high specific IgG titers (up to 105), comparable to intramuscular RBD immunization. Both conjugates showed statistically significant enhancement of the immune response compared to intranasal administration of free RBD (p ≤ 0.05). However, the response proved to be heterogenous among animals, with some mice exhibiting a weak immune response, likely due to intranasal delivery variability. RBD-protein A conjugates elicit a robust IgG response upon intranasal administration, comparable to intramuscular immunization, confirming the adjuvant properties of protein A. Both conjugation methods (Sulfo-SMCC and EDC) were equally effective. Despite response variability due to different to mucosal delivery, these findings support the potential of protein A in developing intranasal vaccines against SARS-CoV-2.
Full Text
##article.viewOnOriginalSite##About the authors
Ekaterina A. Volosnikova
State Research Center of Virology and Biotechnology “Vector”
Author for correspondence.
Email: volosnikova_ea@vector.nsc.ru
PhD (Biology), Senior Researcher, Department of Technology Development and Pilot Production of Biopreparations
Russian Federation, Koltsovo, Novosibirsk RegionN. V. Volkova
State Research Center of Virology and Biotechnology “Vector”
Email: volosnikova_ea@vector.nsc.ru
PhD (Biology), Researcher, Laboratory of Molecular and Synthetic Biology
Russian Federation, Koltsovo, Novosibirsk RegionS. I. Gayvoronskiy
State Research Center of Virology and Biotechnology “Vector”
Email: volosnikova_ea@vector.nsc.ru
Intern Researcher, Laboratory of Molecular and Synthetic Biology
Russian Federation, Koltsovo, Novosibirsk RegionO. V. Simakova
State Research Center of Virology and Biotechnology “Vector”
Email: volosnikova_ea@vector.nsc.ru
Junior Researcher, Department of Biological Studies
Russian Federation, Koltsovo, Novosibirsk RegionT. I. Esina
State Research Center of Virology and Biotechnology “Vector”
Email: volosnikova_ea@vector.nsc.ru
Researcher, Department of Technology Development and Pilot Production of Biopreparations
Russian Federation, Koltsovo, Novosibirsk RegionA. A. Rar
State Research Center of Virology and Biotechnology “Vector”
Email: volosnikova_ea@vector.nsc.ru
Engineer Microbiologist, Department of Technology Development and Pilot Production of Biopreparations
Russian Federation, Koltsovo, Novosibirsk RegionD. N. Shcherbakov
State Research Center of Virology and Biotechnology “Vector”
Email: volosnikova_ea@vector.nsc.ru
Leading Researcher, Head, Laboratory of Molecular and Synthetic Biology
Russian Federation, Koltsovo, Novosibirsk RegionReferences
- Андреев Ю.Ю., Топтыгина А.П. Адъюванты и иммуномодуляторы в составе вакцин // Иммунология, 2021. Т. 42, № 6. С. 720-729. [Andreev Y.Y., Toptygina A.P. Adjuvants and immunomodulators in vaccines. Immunologiya = Immunologiya, 2021, Vol. 42, no. 6, pp. 720-729. (In Russ.)]
- Дьякон А.В., Хрыкина И.С., Хегай А.А., Дьяченко И.А., Мурашев А.Н., Ивашев М.Н. Метод забора крови у животных // Международный журнал прикладных и фундаментальных исследований, 2013. Т. 11, № 1. С. 84-85. [Dyakon A.V., Khrykina I.S., Khegay A.A., Dyachenko I.A., Murashev A.N., Ivashev M.N. Method of blood sampling in animals. Mezhdunarodnyi zhurnal prikladnykh i fundamentalnykh issledovaniy = International Journal of Applied and Fundamental Research, 2013, Vol. 11, no. 2, pp. 84-85. (In Russ.)]
- Borges O., Borchard G. Mucosal vaccination: opportunities and challenges. In: Singh M. (ed.). Novel immune potentiators and delivery technologies for next generation vaccines. Springer US, 2013, pp. 65-80.
- Eriksson K., Holmgren J. Recent advances in mucosal vaccines and adjuvants. Curr. Opin. Immunol., 2002, Vol. 14, no. 5, pp. 666-672.
- Holmgren J., Czerkinsky C. Mucosal immunity and vaccines. Nat. Med., 2005, Vol. 11, no. 4 Suppl., pp. S45-S53. doi: 10.1038/nm1213.
- Kim M.Y., Vergara E., Tran A., Paul M.J., Kwon T.H., Ma J.K.C., Jang Y.S., Reljic R. Marked enhancement of the immunogenicity of plant-expressed IgG-Fc fusion proteins by inclusion of cholera toxin non-toxic B subunit within the single polypeptide. Plant Biotechnol. J., 2024, Vol. 22, no. 5, pp. 1402-1416. doi: 10.1111/pbi.14275.
- Li M., Wang Y., Sun Y., Cui H., Zhu S.J., Qiu H.J. Mucosal vaccines: Strategies and challenges. Immunol. Lett., 2020, Vol. 217, pp. 116-125.
- Lycke N. Recent progress in mucosal vaccine development: Potential and limitations. Nat. Rev. Immunol., 2012, Vol. 12, pp. 592-605.
- Puga-Gómez R., Ricardo-Delgado Y., Rojas-Iriarte C., Céspedes-Henriquez L., Piedra-Bello M., Vega-Mendoza D., Pérez N.P., Paredes-Moreno B., Rodríguez-González M., Valenzuela-Silva C., Sánchez-Ramírez B., Rodríguez-Noda L, Pérez-Nicado R., González-Mugica R., Hernández-García T., Fundora-Barrios T., Echevarría M.D., Enriquez-Puertas J.M., Infante-Hernández Y., Palenzuela-Díaz A., Gato-Orozco E., Chappi-Estévez Y., Francisco-Pérez J.C., Suarez-Martinez M., Castillo-Quintana I.C., Fernandez-Castillo S., Climent-Ruiz Y., Santana-Mederos D., García-Vega Y., Toledo-Romani M.E., Doroud D., Biglari A., Valdés-Balbín Y., García-Rivera D., Vérez-Bencomo V.; SOBERANA Research Group. Open-label phase I/II clinical trial of SARS-CoV-2 receptor binding domain-tetanus toxoid conjugate vaccine (FINLAY-FR-2) in combination with receptor binding domain-protein vaccine (FINLAY-FR-1A) in children. Int. J. Infect. Dis., 2023, Vol. 126, pp. 164-173.
- Silverman G.J., Goodyear C.S., Siegel D.L. On the mechanism of staphylococcal protein A immunomodulation. Transfusion, 2005, Vol. 45, no. 2, pp. 274-280.
- Xing M., Hu G., Wang X., Wang Y., He F., Dai W., Wang X., Niu Y., Liu J., Liu H., Zhang X., Xu J., Cai Q., Zhou D. An intranasal combination vaccine induces systemic and mucosal immunity against COVID-19 and influenza. NPJ Vaccines, 2024, Vol. 9, no. 1, 64. doi: 10.1038/s41541-024-00857-5.
- Yuki Y., Kiyono H. Mucosal vaccines: novel advances in technology and delivery. Expert Rev. Vaccines, 2009, Vol. 8, no. 8, pp. 1083-1097.
- Zhao T., Liu S., Wang P., Zhang Y., Kang X., Pan X., Li L., Li D., Gao P., An Y., Song H., Liu K., Qi J., Zhao X., Dai L., Liu P., Wang P., Wu G., Zhu T., Xu K., Li Y., Gao G.F. Protective RBD-dimer vaccines against SARS-CoV-2 and its variants produced in glycoengineered Pichia pastoris. PLoS Pathog., 2024, Vol. 20, no. 8, e1012487. doi: 10.1371/journal.ppat.1012487.
Supplementary files
