title: Chimeric virus-like particles containing influenza HA antigen and GPI-CCL28 induce long-lasting mucosal immunity against H3N2 viruses.
abstract: 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.
authors.affiliation: Center for Inflammation, Immunity &Infection, Institute for Biomedical Sciences, Georgia State University, 100 Piedmont Ave SE, Atlanta, GA 30303, USA.
authors.forename: Teena
authors.initials: T
authors.lastname: Mohan
authors.affiliation: Center for Inflammation, Immunity &Infection, Institute for Biomedical Sciences, Georgia State University, 100 Piedmont Ave SE, Atlanta, GA 30303, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Berman
authors.affiliation: Center for Inflammation, Immunity &Infection, Institute for Biomedical Sciences, Georgia State University, 100 Piedmont Ave SE, Atlanta, GA 30303, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Center for Inflammation, Immunity &Infection, Institute for Biomedical Sciences, Georgia State University, 100 Piedmont Ave SE, Atlanta, GA 30303, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Microbiology &Immunology, School of Medicine Emory University, 1518 Clifton Road, Atlanta, GA 30322, USA.
authors.forename: Shelly
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Microbiology &Immunology, School of Medicine Emory University, 1518 Clifton Road, Atlanta, GA 30322, USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Compans
authors.affiliation: Center for Inflammation, Immunity &Infection, Institute for Biomedical Sciences, Georgia State University, 100 Piedmont Ave SE, Atlanta, GA 30303, USA.
authors.forename: Bao-Zhong
authors.initials: BZ
authors.lastname: Wang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D019742:Chemokines, CC / Q000276:immunology*; D005260:Female; D058851:GPI-Linked Proteins / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D008807:Mice, Inbred BALB C; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000276:immunology*
chemical_list: C511142:Ccl28 protein, mouse; D019742:Chemokines, CC; D058851:GPI-Linked Proteins; D058425:Vaccines, Virus-Like Particle