Capsid virus-like particle display improves recombinant influenza neuraminidase antigen stability and immunogenicity in mice
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Supplementing influenza vaccines with additional protective antigens such as neuraminidase (NA) is a promising strategy for increasing the breadth of the immune response. Here, we improved the immunogenicity and stability of secreted recombinant NA (rNA) tetramers by covalently conjugating them onto the surface of AP205 capsid virus-like particles (cVLPs) using a Tag/Catcher ligation system. cVLP display increased the induction of IgG2a subclass anti-NA antibodies, which exhibited cross-reactivity with an antigenically distant homologous NA. It also reduced the single dose rNA amounts needed for protection against viral challenge in mice, demonstrating a dose-sparing effect. Moreover, effective cVLP-display was achieved across different NA subtypes, even when the conjugation was performed shortly before administration. Notably, the rNA-cVLP immunogenicity was retained upon mixing or co-administering with commercial vaccines. These results highlight the potential of this approach for bolstering the protective immune responses elicited by influenza vaccines.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 110038 |
| Tidsskrift | iScience |
| Vol/bind | 27 |
| Udgave nummer | 6 |
| Antal sider | 17 |
| ISSN | 2589-0042 |
| DOI | |
| Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:
We would like to thank members of the Division of Viral Products at the Center for Biologics Evaluation and Research (CBER), especially Dr. Gabriel Parra and Dr. Jason Gorman for the critical reading of the article and Drs. Amy Rosenberg, Hana Golding, and Jerry Weir for suggestions. We are grateful to Dr. Timothy Burgess (Uniformed Services University of the Health Sciences, MD), Dr. Srihari Seshadri and Connie Lohls (Defense Health Agency, VA), for providing the commercial influenza vaccines and the entire staff of the Division of Veterinary Services at CBER for extraordinary animal care, especially Amy Guardado for technical support and advice. This work was supported by Intramural funding to R.D. from CBER at the US Food and Drug Administration as well as by Innovation Fund Denmark (grant number 8088-00032B) to A.F.S. All author contributions are an informal communication and represent their own best judgment. These comments do not bind or obligate FDA. A.F.S. and R.D. conceived and supervised the study. H.K. M.R.M. K.L.A. A.K.O. and S.C. performed the investigation and formal analysis. H.W. and T.M. helped with the methodology and provided resources. A.F.S. and R.D. wrote the original draft and all authors reviewed and edited the final draft. A.F.S. is listed as co-inventor on a patent application covering the AP205 cVLP vaccine platform technology (WO2016112921 A1) and is an employee, founder, and shareholder of AdaptVac, a company commercializing cVLP technology.
Funding Information:
We would like to thank members of the Division of Viral Products at the Center for Biologics Evaluation and Research (CBER), especially Dr. Gabriel Parra and Dr. Jason Gorman for the critical reading of the article and Drs. Amy Rosenberg, Hana Golding, and Jerry Weir for suggestions. We are grateful to Dr. Timothy Burgess (Uniformed Services University of the Health Sciences, MD), Dr. Srihari Seshadri and Connie Lohls (Defense Health Agency, VA), for providing the commercial influenza vaccines and the entire staff of the Division of Veterinary Services at CBER for extraordinary animal care, especially Amy Guardado for technical support and advice. This work was supported by Intramural funding to R.D. from CBER at the US Food and Drug Administration as well as by Innovation Fund Denmark (grant number 8088-00032B ) to A.F.S.
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© 2024
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