Richel E, Wagner J, Klessing S, Di Vincenzo R, Temchura V, Überla K (2023)
Publication Type: Journal article
Publication year: 2023
Book Volume: 14
Article Number: 1275193
DOI: 10.3389/fimmu.2023.1275193
Background: Fc-fusion proteins have been successfully developed for therapeutic purposes, but are also a promising platform for the fast generation and purification of immunogens capable of inducing strong humoral immune responses in preclinical immunization studies. As the Fc-portion of immunoglobulins fused to an antigen confers functional properties of the parental antibody, such as dimerization, binding to Fc-receptors and complement activation, several studies reported that Fc-fusion proteins elicit stronger antigen-specific antibody responses than the unfused antigen. However, dimerization or half-life extension of an antigen have also been described to enhance immunogenicity. Methods: To explore the role of Fc-effector functions for the immunogenicity of fusions proteins of viral glycoproteins and Fc fragments, the HIV-1 gp120 and the RBD of SARS-CoV-2 were fused to the wild type muIgG2a Fc fragment or mutants with impaired (LALA-PG) or improved (GASDIE) Fc-effector functions. Results: Immunization of BALB/c mice with DNA vaccines encoding gp120 – Fc LALA-PG induced significantly higher antigen-specific antibody responses than gp120 – Fc WT and GASDIE. In contrast, immunization with DNA vaccines encoding the RBD fused to the same Fc mutants, resulted in comparable anti-RBD antibody levels and similar neutralization activity against several SARS-CoV-2 variants. Conclusion: Depending on the antigen, Fc-effector functions either do not modulate or suppress the immunogenicity of DNA vaccines encoding Fc-antigen fusion proteins.
APA:
Richel, E., Wagner, J., Klessing, S., Di Vincenzo, R., Temchura, V., & Überla, K. (2023). Antigen-dependent modulation of immune responses to antigen-Fc fusion proteins by Fc-effector functions. Frontiers in Immunology, 14. https://doi.org/10.3389/fimmu.2023.1275193
MLA:
Richel, Elie, et al. "Antigen-dependent modulation of immune responses to antigen-Fc fusion proteins by Fc-effector functions." Frontiers in Immunology 14 (2023).
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