Synthetic vaccine affords full protection to mice against lethal challenge of influenza B virus of both genetic lineages

Abstract

HighlightsThe evolution of influenza B viruses necessitates development of universal vaccines

Universal antibody targeting the highly conserved fusion peptide provides cross-protection in mice

“… 37–42 , 77 , 78 Here, we found that Uni-1, a mono-specific antibody targeting the universally conserved linear epitope, could induce strong ADCC and in vivo protection, a new observation consistent with our recent vaccine studies showing deletion of the fusion peptide could reduce the ADCC as well as weaken the vaccine efficacy induced by a HA2 vaccine. 27 The ADCC activity, along with neutralizing activities, 25 could collectively contribute to the effective protection of animals from lethal challenges of both IAV and IBV as presented in this short report.…”

“…Specifically, MDCK cells were infected with several strains of IAV, including H1N1, H3N2, H7N7, and H11N6, and IBV, including B/Victoria (Victoria lineage), B/Brisbane (Victoria lineage), B/Yamagata (Yamagata lineage), and B/Florida (Yamagata lineage) before incubation with Uni-1 and FcγRIV effector cells. 27 …”

“…This finding is in agreement with our recent observation where a HA2-based prototype universal vaccine with the N -terminal deleted resulted in a significant reduction in ADCC effector functions as well as in vivo protection. 27 Moreover, Uni-1 was not found to neutralize IBV in vitro but both groups of IAV. 35 Here, Uni-1 was found to induce significant ADCC response against IBV ( Figure 2 ) and provide complete protection in mice against a lethal challenge ( Figure 3(b) ), suggesting effector functions of Uni-1 are sufficient to fully protect the mice from lethal challenge by IBV.…”

“…Either type can be dominant in a given season, causing disease with comparable severity. 27 Current quadrivalent vaccines provide strain-specific protection against two IAV and two IBV strains; the vaccines mainly elicit neutralizing antibodies (nAbs) targeting the variable HA1 subunit. As the strains are selected several months ahead of the influenza season, mismatch between the vaccine seeds and the actual circulating viruses could happen, resulting in significant reduction of vaccine effectiveness.…”

Cross-Protection Induced by Virus-like Particles Derived from the Influenza B Virus

“…Considering the ease of administration, intramuscular VLP immunization could serve as an alternative to these methods. A recombinant adenovirus vaccine expressing the synthetic HA2 antigen was shown to be effective against influenza B virus infection, as the vaccine enhanced the live GC B cell percentages in the draining lymph nodes and reduced the lung viral loads in mice [ 49 ]. Although GC B cell populations were assessed in a different organ in our study, notably the lung as it is the primary infection site, the results were similar as significantly incremental changes in GC B cell populations were observed.…”