Youhanna 2025 collated expert opinions on the importance of NA in influenza vaccines in a two-stage Delphi survey. Results indicated that anti-NA responses induced by infection or vaccination are associated with protective immunity independently of HA and that NA provided additional advantages including improving disease severity metrics. The experts identified several knowledge gaps concerning heterologous cross-reactivity of vaccine-induced anti-NA Abs, correlations between anti-NA titres and reduced transmission or infection risks, and differences in anti-NA responses to seasonal influenza vaccines.
Cortés 2024 demonstrated that recombinant NA (rNA) protein is highly immunogenic in both naïve mice and ferrets, as well as in pre-immune ferrets, irrespective of the level of match with preexisting immunity, and that the addition of rNA components is a viable option to increase the immunogenicity and potential efficacy of already licensed influenza vaccines by means of boosting NA immunity.
Guzman Ruiz 2024 compared the efficacy of NA vaccination in a mouse model administered either as soluble protein or displayed on the surface of VLP vaccine platforms. Results showed that exposure of the N2 on the VLP surface results in strong anti-NA immunity and protection from lethal influenza virus infection.
Hoy 2024 conducted household transmission studies in Managua, Nicaragua, to examine the impact of anti-NA Abs on influenza A/H3N2 susceptibility and infectivity. Results showed that influenza vaccines designed to elicit NA immunity in addition to HA immunity may not only contribute to protection against infection but also reduce infectivity in a household transmission setting.
Wong 2024 used a new reverse genetics system to generate hybrid LAIV reassortants with HA and NA genes belonging to the opposite IBV lineages, in a new approach to develop IBV vaccines with broad cross-protection.
Daulagala 2023 characterized the NA antigenicity of seasonal A(H1N1) viruses from 1977 to 1991 to complete the NA antigenic profile of A(H1N1) and A(H1N1)pdm09 viruses circulating in humans. Comparisons of imprinting patterns of anti-HA and anti-NA Ab responses indicated broader cross-reactivity of anti-NA Ab responses than anti-HA Ab responses, supporting the inclusion of NA protein in influenza vaccine preparation to enhance vaccine efficacy.
Rosu 2022 demonstrated the potential of NA immunity to protect against disease, virus replication in the lower respiratory tract, and virus shedding in the ferret model.
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Strohmeier 2022 (NIAID/CIVICs rNA vaccine development) characterized the immunogenicity of CpG 1018-adjuvanted rNA vaccines (N1-MPP, N2-MPP, and B-NA-MPP) in a naïve mouse model. CpG 1018-adjuvanted rNA vaccines induced strong and robust immune response against NA, and provided full protection after high lethal challenges in vivo.
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Gao 2021 found that optimizing the design of rNA (via tetramerization motifs and NA domains included in the rNA construct design) affects the immunogenicity and protective efficacy of the influenza vaccine in mice.
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Kawai 2021 found that NA antigen in an intranasal vaccine confers broad cross-protection in the upper respiratory tract by inducing NA-specific IgA that recognizes a wide range of epitopes in mice.