A recombinant N2 neuraminidase-based CpG 1018® adjuvanted vaccine provides protection against challenge with heterologous influenza viruses in mice and hamsters

Irene Hoxie; Kirill Vasilev; Jordan J Clark; Kaitlyn Bushfield; Benjamin Francis; Madhumathi Loganathan; John D Campbell; Dong Yu; Lizheng Guan; Chunyang Gu; Shufang Fan; S Mark Tompkins; Gabriele Neumann; Yoshihiro Kawaoka; Florian Krammer

doi:10.1016/j.vaccine.2024.126269

A recombinant N2 neuraminidase-based CpG 1018® adjuvanted vaccine provides protection against challenge with heterologous influenza viruses in mice and hamsters

Vaccine. 2024 Oct 24;42(24):126269. doi: 10.1016/j.vaccine.2024.126269. Epub 2024 Sep 5.

Authors

Affiliations

¹ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY, USA.
² Dynavax Technologies Corporation, Emeryville, CA, USA.
³ Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
⁴ Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA; Center for Influenza Disease and Emergence Response (CIDER), University of Georgia, Athens, GA 30602, USA; Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA.
⁵ Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA; Department of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan; The University of Tokyo Pandemic Preparedness, Infection and Advanced research center (UTOPIA), Tokyo, Japan.
⁶ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research, Medical University of Vienna, Vienna, Austria. Electronic address: florian.krammer@mssm.edu.

PMID: 39241354
DOI: 10.1016/j.vaccine.2024.126269

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.

Keywords: Influenza; Neuraminidase; Neuraminidase inhibition; TLR9 agonist; Vaccine.

MeSH terms

Adjuvants, Immunologic* / administration & dosage
Adjuvants, Vaccine
Alum Compounds / administration & dosage
Animals
Antibodies, Viral* / blood
Antibodies, Viral* / immunology
Cricetinae
Cross Protection / immunology
Disease Models, Animal
Female
Immunity, Cellular
Influenza Vaccines* / administration & dosage
Influenza Vaccines* / immunology
Mesocricetus
Mice
Mice, Inbred BALB C
Neuraminidase* / genetics
Neuraminidase* / immunology
Oligodeoxyribonucleotides / administration & dosage
Oligodeoxyribonucleotides / immunology
Orthomyxoviridae Infections* / immunology
Orthomyxoviridae Infections* / prevention & control
Vaccines, Synthetic / administration & dosage
Vaccines, Synthetic / immunology

Substances

Influenza Vaccines
Neuraminidase
Adjuvants, Immunologic
Antibodies, Viral
Vaccines, Synthetic
Adjuvants, Vaccine
Oligodeoxyribonucleotides
Alum Compounds
aluminum sulfate