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

• Type of Material: Article
• Authors: Teena Mohan, Georgia State University; Zachary Berman, Georgia State University; Yuan Luo, Georgia State University; Chao Wang, Georgia State University; Shelly Wang, Emory University; Richard Compans, Emory University; Bao-Zhong Wang, Georgia State University
• Language: English
• Date: 2017-01-09
• Publisher: Nature Publishing Group: Open Access Journals - Option C
• Publication Version: Final Published Version
• Copyright Statement: © 2017, The Author(s)
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/srep40226
• Title of Journal or Parent Work: Scientific Reports
• ISSN: 2045-2322
• Volume: 7
• Start Page: 40226
• End Page: 40226
• Grant/Funding Information: This study was supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the NIH under grants R01AI10104 and R01AI116835 to BZW.
• Keywords: Science & Technology - Other Topics; PROTECTIVE IMMUNITY; VACCINE; RESPIRATORY-TRACT; INFECTION; IGA ANTIBODIES; Science & Technology; Multidisciplinary Sciences; CUTTING EDGE; A VIRUS; MICE; CELLS; CROSS-PROTECTION
• Research Categories: Biology, Microbiology; Health Sciences, Immunology

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.