Capsid virus-like particle display improves recombinant influenza neuraminidase antigen stability and immunogenicity in mice
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Capsid virus-like particle display improves recombinant influenza neuraminidase antigen stability and immunogenicity in mice. / Kang, Hyeog; Martinez, Mira Rakic; Aves, Kara Lee; Okholm, Anna Kathrine; Wan, Hongquan; Chabot, Sylvie; Malik, Tahir; Sander, Adam F.; Daniels, Robert.
I: iScience, Bind 27, Nr. 6, 110038, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Capsid virus-like particle display improves recombinant influenza neuraminidase antigen stability and immunogenicity in mice
AU - Kang, Hyeog
AU - Martinez, Mira Rakic
AU - Aves, Kara Lee
AU - Okholm, Anna Kathrine
AU - Wan, Hongquan
AU - Chabot, Sylvie
AU - Malik, Tahir
AU - Sander, Adam F.
AU - Daniels, Robert
N1 - Publisher Copyright: © 2024
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Biological sciences
KW - Immune response
KW - Immunology
KW - Natural sciences
U2 - 10.1016/j.isci.2024.110038
DO - 10.1016/j.isci.2024.110038
M3 - Journal article
AN - SCOPUS:85194728372
VL - 27
JO - iScience
JF - iScience
SN - 2589-0042
IS - 6
M1 - 110038
ER -
ID: 394715196