Job ER, et al. Broadened immunity against influenza by vaccination with computationally designed influenza virus N1 neuraminidase constructs. NPJ Vaccines. 2018 Nov 29;3:55
Split inactivated influenza vaccines remain one of the primary preventative strategies against severe influenza disease in the population. However, current vaccines are only effective against a limited number of matched strains. The need for broadly protective vaccines is acute due to the high mutational rate of influenza viruses and multiple strain variants in circulation at any one time. The neuraminidase (NA) glycoprotein expressed on the influenza virion surface has recently regained recognition as a valuable vaccine candidate. We sought to broaden the protection provided by NA within the N1 subtype by computationally engineering consensus NA sequences. Three NA antigens (NA5200, NA7900, NA9100) were designed based on sequence clusters encompassing three major groupings of NA sequence space; (i) H1N1 2009 pandemic and Swine H1N1, (ii) historical seasonal H1N1 and (iii) H1N1 viruses ranging from 1933 till current times. Recombinant NA proteins were produced as a vaccine and used in a mouse challenge model. The design of the protein dictated the protection provided against the challenge strains. NA5200 protected against H1N1 pdm09, a Swine isolate from 1998 and NIBRG-14 (H5N1). NA7900 protected against all seasonal H1N1 viruses tested, and NA9100 showed the broadest range of protection covering all N1 viruses tested. By passive transfer studies and serological assays, the protection provided by the cluster-based consensus (CBC) designs correlated to antibodies capable of mediating NA inhibition. Importantly, sera raised to the consensus NAs displayed a broader pattern of reactivity and protection than naturally occurring NAs, potentially supporting a predictive approach to antigen design.
See Also:
Latest articles in those days:
- Influenza hijacks myeloid cells to inflict type-I interferon-fueled damage in the heart 15 minute(s) ago
- MHC class II functions as a host-specific entry receptor for representative human and swine H3N2 influenza A viruses 17 minute(s) ago
- Longitudinal Surveillance of Influenza A Virus Exposure in Wild Boars (Sus scrofa) in Spain (2015-2023): Serologic and Virologic Evidence of Subtype Infections and H5N1 Spillover Risk 19 minute(s) ago
- [preprint]Emergence and antigenic characterisation of influenza A(H3N2) viruses with hemagglutinin substitutions N158K and K189R during the 2024/25 influenza season 20 hours ago
- Epitope specificity shapes the CD4+ T cell response to influenza virus infection in mice 20 hours ago
[Go Top] [Close Window]


