Email this article 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
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Affiliations:
- State Research Center of Virology and Biotechnology “Vector”
- Section: Immunological readings in Chelyabinsk
- Submitted: 28.03.2025
- Accepted: 25.05.2025
- URL: https://rusimmun.ru/jour/article/view/17148
- DOI: https://doi.org/10.46235/1028-7221-17148-PAA
- ID: 17148
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Abstract
Abstract
Objective. To study the 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.
Materials and methods. 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 was performed on 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).
Results. 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, response heterogeneity was observed among animals, with some mice exhibiting a weak immune response, likely due to intranasal delivery variability.
Conclusions. 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 linked to mucosal delivery, these findings support the potential of protein A in developing intranasal vaccines against SARS-CoV-2.
About the authors
Ekaterina Alexandrovna Volosnikova
State Research Center of Virology and Biotechnology “Vector”
Email: kulenok84@mail.ru
ORCID iD: 0000-0001-5028-5647
SPIN-code: 9548-7439
Scopus Author ID: 36626467100
Leading Researcher, Head of the Departament of Technology Development and Pilot Production of Biologicals
Russian Federation, 630559, Koltsovo, Novosibirsk region, Russian FederationNatalia Vyacheslavovna Volkova
State Research Center of Virology and Biotechnology “Vector”
Email: tasha_wolkowa11.93@mail.ru
ORCID iD: 0000-0001-5010-9424
Candidate of Science (Biology)
Researcher at the Laboratory of Molecular and Synthetic Biology
Russian Federation, 630559, Koltsovo, Novosibirsk region, Russian FederationSergey Igorevich Gayvoronskiy
State Research Center of Virology and Biotechnology “Vector”
Email: gsi0902@mail.ru
ORCID iD: 0009-0004-0276-7229
Intern researcher at the Laboratory of Molecular and Synthetic Biology
Russian Federation, 630559, Koltsovo, Novosibirsk region, Russian FederationOlga Vladimirovna Simakova
State Research Center of Virology and Biotechnology “Vector”
Email: simakova_ov@vector.nsc.ru
ORCID iD: 0000-0002-1222-7574
SPIN-code: 6507-5706
Scopus Author ID: 58095900900
Junior researcher at the Department of Biological Studies
Russian Federation, 630559, Koltsovo, Novosibirsk region, Russian FederationTatiana Igorevna Esina
State Research Center of Virology and Biotechnology “Vector”
Email: esina_ti@vector.nsc.ru
ORCID iD: 0000-0001-9006-8313
SPIN-code: 8342-0830
Scopus Author ID: 57190121468
Researcher at the Departament of Technology Development and Pilot Production of Biologicals
Russian Federation, 630559, Koltsovo, Novosibirsk region, Russian FederationAnastasia Anatolevna Rar
State Research Center of Virology and Biotechnology “Vector”
Email: rar_aa@vector.nsc.ru
ORCID iD: 0009-0000-2652-8434
Engineer microbiologist at the Departament of Technology Development and Pilot Production of Biologicals
Russian Federation, 630559, Koltsovo, Novosibirsk region, Russian FederationDmitry Nikolaevich Shcherbakov
State Research Center of Virology and Biotechnology “Vector”
Author for correspondence.
Email: dnshcherbakov@gmail.com
ORCID iD: 0000-0001-8023-4453
SPIN-code: 9616-0933
Scopus Author ID: 37027118800
Candidate of Science (Biology)
Leading Researcher, Head of the Laboratory of Molecular and Synthetic Biology
Russian Federation, 630559, Koltsovo, Novosibirsk region, Russian FederationReferences
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СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).