Chimeric virus-like particles containing influenza HA antigen and GPI-CCL28 induce long-lasting mucosal immunity against H3N2 viruses. 2017

Teena Mohan, and Zachary Berman, and Yuan Luo, and Chao Wang, and Shelly Wang, and Richard W Compans, and Bao-Zhong Wang
Center for Inflammation, Immunity &Infection, Institute for Biomedical Sciences, Georgia State University, 100 Piedmont Ave SE, Atlanta, GA 30303, USA.

Influenza virus is a significant cause of morbidity and mortality, with worldwide seasonal epidemics. The duration and quality of humoral immunity and generation of immunological memory to vaccines is critical for protective immunity. In the current study, we examined the long-lasting protective efficacy of chimeric VLPs (cVLPs) containing influenza HA and GPI-anchored CCL28 as antigen and mucosal adjuvant, respectively, when immunized intranasally in mice. We report that the cVLPs induced significantly higher and sustainable levels of virus-specific antibody responses, especially IgA levels and hemagglutination inhibition (HAI) titers, more than 8-month post-vaccination compared to influenza VLPs without CCL28 or influenza VLPs physically mixed with sCCL28 (soluble) in mice. After challenging the vaccinated animals at month 8 with H3N2 viruses, the cVLP group also demonstrated strong recall responses. On day 4 post-challenge, we measured increased antibody levels, ASCs and HAI titers with reduced viral load and inflammatory responses in the cVLP group. The animals vaccinated with the cVLP showed 20% cross-protection against drifted (Philippines) and 60% protection against homologous (Aichi) H3N2 viruses. Thus, the results suggest that the GPI-anchored CCL28 induces significantly higher mucosal antibody responses, involved in providing long-term cross-protection against H3N2 influenza virus when compared to other vaccination groups.

UI MeSH Term Description Entries
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000281 Administration, Intranasal Delivery of medications through the nasal mucosa. Drug Administration, Intranasal,Administration, Intranasal Drug,Administration, Nasal,Intranasal Administration,Intranasal Drug Administration,Administrations, Intranasal,Administrations, Intranasal Drug,Administrations, Nasal,Drug Administrations, Intranasal,Intranasal Administrations,Intranasal Drug Administrations,Nasal Administration,Nasal Administrations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D053122 Influenza A Virus, H3N2 Subtype A subtype of INFLUENZA A VIRUS comprised of the surface proteins hemagglutinin 3 and neuraminidase 2. The H3N2 subtype was responsible for the Hong Kong flu pandemic of 1968. H3N2 Virus,H3N2v Viruses,Influenza A H3N2, Variant Virus,Influenza Virus, Canine, H3N2 Subtype,H3N2 Viruses,H3N2v Virus,Virus, H3N2,Virus, H3N2v,Viruses, H3N2,Viruses, H3N2v
D058425 Vaccines, Virus-Like Particle Vaccines using supra-molecular structures composed of multiple copies of recombinantly expressed viral structural proteins. They are often antigentically indistinguishable from the virus from which they were derived. Virus-Like Particle Vaccine,Virus-Like Particle Vaccines,Particle Vaccine, Virus-Like,Particle Vaccines, Virus-Like,Vaccine, Virus-Like Particle,Vaccines, Virus Like Particle,Virus Like Particle Vaccine,Virus Like Particle Vaccines
D058851 GPI-Linked Proteins A subclass of lipid-linked proteins that contain a GLYCOSYLPHOSPHATIDYLINOSITOL LINKAGE which holds them to the CELL MEMBRANE. GPI-Anchored Proteins,GPI-Linked Membrane Proteins,Glycosylphosphatidylinositol Linked Proteins,GPI Anchored Proteins,GPI Linked Membrane Proteins,GPI Linked Proteins,Membrane Proteins, GPI-Linked,Proteins, GPI-Anchored,Proteins, GPI-Linked,Proteins, GPI-Linked Membrane,Proteins, Glycosylphosphatidylinositol Linked
D018928 Immunity, Mucosal Nonsusceptibility to the pathogenic effects of foreign microorganisms or antigenic substances as a result of antibody secretions of the mucous membranes. Mucosal epithelia in the gastrointestinal, respiratory, and reproductive tracts produce a form of IgA (IMMUNOGLOBULIN A, SECRETORY) that serves to protect these ports of entry into the body. Immune Response, Mucosal,Mucosal Immunity,Immune Responses, Mucosal,Mucosal Immune Response,Mucosal Immune Responses
D019742 Chemokines, CC Group of chemokines with adjacent cysteines that are chemoattractants for lymphocytes, monocytes, eosinophils, basophils but not neutrophils. C-C Chemokine,CC Chemokine,CC Chemokines,beta-Chemokine,beta-Chemokines,C-C Chemokines,C C Chemokine,C C Chemokines,Chemokine, C-C,Chemokine, CC,Chemokines, C-C,beta Chemokine,beta Chemokines

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