Capsid virus-like particle display improves recombinant influenza neuraminidase antigen stability and immunogenicity in mice
Hyeog Kang,
Mira Rakic Martinez,
Kara-Lee Aves,
Anna Kathrine Okholm,
Hongquan Wan,
Sylvie Chabot,
Tahir Malik,
Adam F. Sander,
Robert Daniels
Affiliations
Hyeog Kang
Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA
Mira Rakic Martinez
Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA
Kara-Lee Aves
Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
Anna Kathrine Okholm
Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
Hongquan Wan
Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA
Sylvie Chabot
Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA
Tahir Malik
Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA
Adam F. Sander
Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark; AdaptVac, Ole Maaløes Vej 3, 2200 Copenhagen, Denmark; Corresponding author
Robert Daniels
Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA; Corresponding author
Summary: 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.
