Neuraminidase (NA), the second most abundant surface glycoprotein on the influenza virus, plays a key role in viral replication and propagation. Despite growing evidence showing that NA-specific antibodies correlate with resistance to disease in humans, current licensed vaccines focus almost entirely on the hemagglutinin (HA) antigen. Here, we demonstrate 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. Ferrets vaccinated with rNA developed mild influenza disease symptoms upon challenge with human H3N2 influenza virus, and anti-NA antibody responses appeared correlated with reduction in disease severity. The addition of rNA to a quadrivalent HA-based vaccine induced robust NA-specific humoral immunity in ferrets, while retaining the ability to induce HA-specific immunity. These results demonstrate that the addition of rNA is a viable option to increase immunogenicity and potentially efficacy versus currently licensed influenza vaccines by means of boosting NA immunity.
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http://dx.doi.org/10.1038/s41541-024-01011-x | DOI Listing |
J Virol
January 2025
Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
Unlabelled: Respiratory and encephalitic virus infections represent a significant risk to public health globally. Detailed investigations of immunological responses and disease outcomes during sequential virus infections are rare. Here, we define the impact of influenza virus infection on a subsequent virus encephalitis.
View Article and Find Full Text PDFOpen Forum Infect Dis
January 2025
Harvard Medical School, Boston, Massachusetts, USA.
Background: Infections by and influenza viruses are vaccine-preventable diseases causing great morbidity and mortality. We evaluated pneumococcal and influenza vaccination practices during pre-international travel health consultations.
Methods: We evaluated data on pretravel visits over a 10-year period (1 July 2012 through 31 June 2022) from 31 sites in Global TravEpiNet (GTEN), a consortium of US healthcare facilities providing pretravel health consultations.
Nat Microbiol
January 2025
State key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Generating effective live vaccines from intact viruses remains challenging owing to considerations of safety and immunogenicity. Approaches that can be applied in a systematic manner are needed. Here we created a library of live attenuated influenza vaccines by using diverse cellular E3 ubiquitin ligases to generate proteolysis-targeting (PROTAR) influenza A viruses.
View Article and Find Full Text PDFNat Chem Biol
January 2025
State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Manipulating viral protein stability using the cellular ubiquitin-proteasome system (UPS) represents a promising approach for developing live-attenuated vaccines. The first-generation proteolysis-targeting (PROTAR) vaccine had limitations, as it incorporates proteasome-targeting degrons (PTDs) at only the terminal ends of viral proteins, potentially restricting its broad application. Here we developed the next-generation PROTAR vaccine approach, referred to as PROTAR 2.
View Article and Find Full Text PDFACS Nano
January 2025
Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Multiple sclerosis (MS) is a severe autoimmune disorder that wreaks havoc on the central nervous system, leading to a spectrum of motor and cognitive impairments. There is no cure, and current treatment strategies rely on broad immunosuppression, leaving patients vulnerable to infections. To address this problem, our approach aims to induce antigen-specific tolerance, a much-needed shift in MS therapy.
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