June 12 – 17, 2022
Influenza viruses undergo antigenic changes in the immuno-dominant hemagglutinin (HA) head domain, necessitating annual re-formulation of and re-vaccination with seasonal influenza virus vaccines for maintaining the protection. We previously synthesized mosaic HA (mHA) proteins of influenza B viruses which redirect the immune response towards the immuno-subdominant conserved epitopes of the B virus HA via sequential immunization. As ~90% of current influenza virus vaccines are manufactured using the inactivated virus platform, we generated and sequentially vaccinated mice with inactivated influenza B viruses displaying either the homologous (same B HA backbones) or the heterologous (different B HA backbones) mosaic HAs. Both approaches induced long-lasting and cross-protective antibody responses showing strong antibody-dependent cellular cytotoxicity (ADCC) activity. Thereafter, we tested different inactivation methods and adjuvants to increase the cross-protection against phylogenetically distant influenza B viruses from both lineages. The use of CpG 1018 or AddaVax boosted the humoral immune response and protection when combined with any inactivation method. Beta-propiolactone (BPL) inactivation was the best method, with high serum HA antibodies levels that correlated with optimal protection in BALB/C mice challenge studies. We believe that these B virus mHA vaccine candidates represent a major step towards a universal influenza B virus vaccine.
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Irene González-Domínguez, Yonghong Liu, Eduard Puente-Massaguer, Nicholas Lemus, Stefan Slamanig, Tsoi Ying Lai, Shirin Strohmeier, Madhumathi Loganathan, Jose Martínez-Guevara, Florian Krammer, Adolfo García-Sastre, Peter Palese, and Weina Sun, "A universal Influenza B vaccine using mosaic-hemagglutinin vaccine candidates" in "Vaccine Technology VIII", Tarit Mukhopadhyay, Merck Research Laboratories, USA; Charles Lutsch, Sanofi Pasteur, France; Linda Hwee-Lin Lua, University of Queensland, Australia; Francesc Godia, Universitat Autònoma de Barcelona, Spain Eds, ECI Symposium Series, (2022). https://dc.engconfintl.org/vaccine_viii/98