Crude inactivated influenza A virus adjuvated with a bispecific antibody complex targeting chicken CD40 and AIV M2e confers protection against lethal HPAI challenge in chickens

Authors: VUONG, CHRISTINE - Texas A&M University; CHOU, WEN-KO - Texas A&M University; BRIGGS, WHITNEY - The Ohio State University; FAULKNER, OLIVIA - University Of Arkansas; WOLFENDEN, AMANDA - University Of Arkansas; JONAS, MELINA - Medion Vaccine Company; Kapczynski, Darrell; HARGIS, BILLY - University Of Arkansas; BIELKE, LISA - The Ohio State University; BERGHMAN, LUC - Texas A&M University

Submitted to: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/25/2018
Publication Date: 12/28/2018
Citation: Vuong, C., Chou, W., Briggs, W., Faulkner, O., Wolfenden, A., Jonas, M., Kapczynski, D.R., Hargis, B.M., Bielke, L.R., Berghman, L.R. 2018. Crude inactivated influenza A virus adjuvated with a bispecific antibody complex targeting chicken CD40 and AIV M2e confers protection against lethal HPAI challenge in chickens. Monoclonal Antibodies in Immunodiagnosis and Immunotherapy. 37(6):245-251. https://doi.org/10.1089/mab.2018.0040.
DOI: https://doi.org/10.1089/mab.2018.0040

Interpretive Summary: Avian influenza (AI) is a viral disease of poultry and detection in commercial flocks result in significant mortality with serious economic impact to the poultry industry. Vaccination against AI is used to increase protection of birds against disease and limit transmission to susceptible cohorts. Because of inherent differences between individual AI virus subtypes, no single vaccine protects against all AI viruses. In addition, inactivated vaccines require an adjuvant to enhance the immune response. The objectives of the present study were to extend the knowledge of vaccine induced protection by developing an adjuvant with superior immune reactivity by targeting specific immune cells. The results demonstrate that the vaccine adjuvants developed here could increase protection and resistance against AI challenge. These results are an important step in further development of better vaccine adjuvants for poultry.

Technical Abstract: In vivo targeting an immunogen to the CD40 receptor expressed on professional antigen-presenting cells (APCs) dramatically enhances speed, magnitude, and quality of the immune response. Our previous evaluation of this strategy in poultry was limited to immunogenicity studies using CD40-targeted synthetic peptides, which demonstrated significant antigen-specific serum IgG and tracheal IgA levels <1 week after primary administration. In this study, this antibody-guided immunization strategy was modified to permit incorporation of inactivated highly pathogenic avian influenza virions (in lieu of short synthetic peptides) as the immunogen by simply mixing a bispecific antibody complex (anti-CD40/M2e) with crude inactivated virus before injection. Adjuvated avian influenza virus (AIV) induced significant hemagglutination inhibition titers up to 6 weeks postimmunization. In efficacy studies, administration of a single vaccine dose yielded 56%–64% survival against challenge with highly pathogenic H5N1, and 100% protection was achieved upon boosting. These results represent a feasible strategy to effectively target whole inactivated influenza A virus to chicken APCs, regardless of AIV clade and without phenotyping or purifying the virus from crude allantoic fluid. The data represent proof of principle for the unique prophylactic efficacy and versatility of a CD40-targeting adjuvation strategy that can in principle also be harnessed in other poultry vaccines.