1. A recombinant N2 neuraminidase-based CpG 1018® adjuvanted vaccine provides protection against challenge with heterologous influenza viruses in mice and hamsters.
- Author
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Hoxie I, Vasilev K, Clark JJ, Bushfield K, Francis B, Loganathan M, Campbell JD, Yu D, Guan L, Gu C, Fan S, Tompkins SM, Neumann G, Kawaoka Y, and Krammer F
- Subjects
- Animals, Mice, Female, Cricetinae, Vaccines, Synthetic immunology, Vaccines, Synthetic administration & dosage, Adjuvants, Vaccine, Mice, Inbred BALB C, Cross Protection immunology, Mesocricetus, Oligodeoxyribonucleotides administration & dosage, Oligodeoxyribonucleotides immunology, Alum Compounds administration & dosage, Disease Models, Animal, Immunity, Cellular, Influenza Vaccines immunology, Influenza Vaccines administration & dosage, Neuraminidase immunology, Neuraminidase genetics, Orthomyxoviridae Infections prevention & control, Orthomyxoviridae Infections immunology, Adjuvants, Immunologic administration & dosage, Antibodies, Viral immunology, Antibodies, Viral blood
- Abstract
Recombinant influenza virus neuraminidase (NA) is a promising broadly protective influenza vaccine candidate. However, the recombinant protein alone is not sufficient to induce durable and protective immune responses and requires the coadministration of immunostimulatory molecules. Here, we evaluated the immunogenicity and cross-protective potential of a recombinant influenza virus N2 neuraminidase vaccine construct, adjuvanted with a toll-like receptor 9 (TLR9) agonist (CpG 1018® adjuvant), and alum. The combination of CpG 1018 adjuvant and alum induced a balanced and robust humoral and T-cellular immune response against the NA, which provided protection and reduced morbidity against homologous and heterologous viral challenges in mouse and hamster models. This study supports Syrian hamsters as a useful complementary animal model to mice for pre-clinical evaluation of influenza virus vaccines., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The Icahn School of Medicine at Mount Sinai has filed patent applications relating to influenza virus vaccines and therapeutics vaccines which list Florian Krammer as co-inventor. Several of these patents have been licensed and Florian Krammer has received royalty payments from commercial entities. Florian Krammer has consulted for Merck, Pfizer, Seqirus, GSK and Curevac and is currently consulting for Gritstone, 3rd Rock Ventures and Avimex and he is a co-founder and scientific advisory board member of CastleVax. The Krammer laboratory is also collaborating with Dynavax on influenza virus vaccine development and with VIR on influenza therapeutics. John D. Campbell and Dong Yu are employees of Dynavax Technologies Corporation and may hold company stock. Yoshihiro Kawaoka has received grant support from Daiichi Sankyo Pharmaceutical, Toyama Chemical, Tauns Laboratories, Shionogi, Otsuka Pharmaceutical, KM Biologics, Kyoritsu Seiyaku, Shinya Corporation, and Fuji Rebio. Yoshihiro Kawaoka and Gabriele Neumann are co-founders of FluGen., (Copyright © 2024. Published by Elsevier Ltd.)
- Published
- 2024
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