Teena Mohan, Compans R W and Wang B
Emory University, USA
Posters & Accepted Abstracts: J Vaccines Vaccin
Influenza infection typically initiates at respiratory mucosal surfaces. Induction of immune responses at the sites where pathogens initiate replication is crucial for the prevention of infection. We studied the adjuvant city of GPI-anchored CCL28 co-incorporated with influenza HA-antigens into virus like particles (VLPs), in boosting strong protective immune responses through an intranasal route in mice. We compared the immune responses to that from influenza VLPs without CCL28, or physically mixed with soluble CCL28 at systemic and various mucosal compartments. The cVLPs containing GPI-CCL28 showed in vitro chemotactic activity towards the cells expressing CCR3/CCR10 chemokine receptors. The GPI-CCL28-containing VLPs induced antigen specific endpoint titers and avidity index of IgG in sera and IgA in tracheal, lung and intestinal secretions, significantly higher (4-6 fold) than other formulations. Significantly higher (3-5 fold) hem agglutination inhibition titers with high serum neutralization against H3N2 viruses were also detected with CCL28-containing VLPs compared to other groups. The CCL28- containing VLPs showed complete and 80% protection, when vaccinated animals were challenged with A/Aichi/2/1968/H3N2 (homologous) or A/Philippines/2/1982/ H3N2 (heterologous) viruses, respectively. Thus, GPI-anchored CCL28 in influenza VLPs act as a strong immunostimulator at both systemic and mucosal sites, boosting significant cross-protection in animals against heterologous viruses across a large distance.
Email: mohan.teena@gmail.com