AS04-adjuvanted virus-like particles containing multiple M2 extracellular domains of influenza virus confer improved protection

• Published in: Vaccine Vol. 32; no. 35; pp. 4578 - 4585
• Main Authors: Lee, Yu-Na, Kim, Min-Chul, Lee, Young-Tae, Hwang, Hye Suk, Cho, Min-Kyoung, Lee, Jong Seok, Ko, Eun-Ju, Kwon, Young-Man, Kang, Sang-Moo
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 31.07.2014; Elsevier; Elsevier Limited
• Subjects: Adjuvants; Adjuvants, Immunologic - administration & dosage; Allergy and Immunology; Aluminum Hydroxide - administration & dosage; Animals; Antibodies, Viral - blood; Applied microbiology; Avian flu; Baculovirus; Biological and medical sciences; C57BL/6; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Cell activation; Cross-protection; Cytokines; Dendritic cells; Disease Models, Animal; Eggs; Female; Fundamental and applied biological sciences. Psychology; Genetic diversity; Histocompatibility antigen H-2; Immune system; Immunogenicity; Immunoglobulin G; Infections; Influenza; Influenza A; Influenza Vaccines - administration & dosage; Influenza Vaccines - genetics; Influenza Vaccines - immunology; Influenza virus; Interferon; Interferon-gamma - metabolism; Ligands; Lipid A - administration & dosage; Lipid A - analogs & derivatives; Lymphocytes; Lymphocytes T; M2e VLPs; Matrix protein; Mice, Inbred C57BL; Microbiology; Miscellaneous; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - prevention & control; Population genetics; Proteins; TLR4 protein; Toll-like receptors; Vaccination; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Virus-Like Particle - administration & dosage; Vaccines, Virus-Like Particle - genetics; Vaccines, Virus-Like Particle - immunology; Viral infections; Viral Matrix Proteins - genetics; Viral Matrix Proteins - immunology; Virology; Virus-like particles; γ-Interferon; Adjuvants; Influenza virus; C57BL/6; M2e VLPs; Virus; Immunological adjuvant; Virus like particle; Orthomyxoviridae; Influenzavirus
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2014.06.040

Abstract The ectodomain of matrix protein 2 (M2e) of influenza virus is suggested to be a rational target for a universal influenza A vaccine. However, there are some concerns that M2e vaccines might not be highly effective in the general population with diverse genetic backgrounds. Here we examined the immunogenicity and protective efficacy of the baculovirus-derived virus-like particles containing multiple M2e (M2eVLP) with AS04 adjuvant in a C57BL/6 mouse strain (H-2b ). M2eVLP vaccine induced significant levels of M2e-specific IgG in C57BL/6 mice after vaccination. Furthermore, M2eVLP adjuvanted with AS04 was more effective than M2eVLP alone in conferring protection as well as in inducing recall humoral and T cell responses specific for M2e after lethal influenza virus challenge. A mechanistic study provides evidence that activation of dendritic cells by the toll-like receptor 4 agonist MPL in the AS04 adjuvant was associated with interferon-γ producing CD4 T cell responses. Our results suggest that AS04 adjuvanted M2eVLP vaccines have the potential to improve cross-protection.