Immunogenicity of a West Nile Virus DIII-Cholera Toxin A2/B Chimera after Intranasal Delivery

Toxins

Juliette K. Tinker¹  Jie Yan²  Reece J. Knippel²  Panos Panayiotou² 

[1] Department of Biological Sciences, Boise State University, Boise, ID 83725, USA;Department of Chemistry and Biochemistry, Boise State University, Boise, ID 83725, USA; E-Mails:

关键词: West Nile virus;    cholera toxin;    vaccine;    mucosal adjuvant;   

DOI  :  10.3390/toxins6041397

来源: mdpi

【 摘 要 】

West Nile virus (WNV) causes potentially fatal neuroinvasive disease and persists at endemic levels in many parts of the world. Despite advances in our understanding of WNV pathogenesis, there remains a significant need for a human vaccine. The domain III (DIII) region of the WNV envelope protein contains epitopes that are the target of neutralizing antibodies. We have constructed a chimeric fusion of the non-toxic cholera toxin (CT) CTA₂/B domains to DIII for investigation as a novel mucosally-delivered WNV vaccine. Purification and assembly of the chimera, as well as receptor-binding and antigen delivery, were verified by western blot, GM1 ELISA and confocal microscopy. Groups of BALB/c mice were immunized intranasally with DIII-CTA₂/B, DIII, DIII mixed with CTA₂/B, or CTA₂/B control, and boosted at 10 days. Analysis of serum IgG after 14 and 45 days revealed that mucosal immunization with DIII-CTA₂/B induced significant DIII-specific humoral immunity and drove isotype switching to IgG2a. The DIII-CTA₂/B chimera also induced antigen-specific IgM and IgA responses. Bactericidal assays indicate that the DIII-CTA₂/B immunized mice produced DIII-specific antibodies that can trigger complement-mediated killing. A dose escalation resulted in increased DIII-specific serum IgG titers on day 45. DIII antigen alone, in the absence of adjuvant, also induced significant systemic responses after intranasal delivery. Our results indicate that the DIII-CTA₂/B chimera is immunogenic after intranasal delivery and merits further investigation as a novel WNV vaccine candidate.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.