Universal Influenza B Vaccine Based on the Maturational Cleavage Site of the Hemagglutinin Precursor

Abstract

Conventional influenza vaccines can prevent infection, but their efficacy depends on the degree of antigenic "match" between the strains used for vaccine preparation and those circulating in the population. A universal influenza vaccine based on invariant regions of the virus, able to provide broadly cross-reactive protection, without requiring continuous manufacturing update, would solve a major medical need. Since the temporal and geographical dominance of the influenza virus type and/or subtype (A/H3, A/H1, or B) cannot yet be predicted, a universal vaccine, like the vaccines currently in use, should include both type A and type B influenza virus components. However, while encouraging preclinical data are available for influenza A virus, no candidate universal vaccine is available for influenza B virus. We show here that a peptide conjugate vaccine, based on the highly conserved maturational cleavage site of the HA 0 precursor of the influenza B virus hemagglutinin, can elicit a protective immune response against lethal challenge with viruses belonging to either one of the representative, non-antigenically cross-reactive influenza B virus lineages. We demonstrate that protection by the HA 0 vaccine is mediated by antibodies, probably through effector mechanisms, and that a major part of the protective response targets the most conserved region of HA 0 , the P1 residue of the scissile bond and the fusion peptide domain. In addition, we present preliminary evidence that the approach can be extended to influenza A virus, although the equivalent HA 0 conjugate is not as efficacious as for influenza B virus.

Cross-protection against drifted influenza viruses

“…About it a preclinical animal model conducted by Bianchi et al demonstrated that using HA0 precursor of the viral HA, epitope widely conserved, as vaccine antigen, high immunogenicity and reduction in viral replications in the lower respiratory tract can be obtained. 49 Alternative strategies demonstrating to improve immune response against influenza drifted strains are represented by adjuvanted vaccines and ID vaccines.…”

A Human CD4+T Cell Epitope in the Influenza Hemagglutinin Is Cross-Reactive to Influenza A Virus Subtypes and to Influenza B Virus

“…This may be advantageous when considering epitopes to be included in an improved vaccine for influenza virus, since more than one HLA molecule can present the peptide. In addition, a peptide conjugate vaccine based on the fusion peptide of the precursor HA of the B virus was shown to elicit protection in mice against lethal challenge of various strains of influenza B virus and can potentially be extended to influenza A virus strains (7). It is also interesting to note that a B cell epitope (3) and an HLA-A2-restricted CD8 ϩ T cell epitope (32) have been previously described.…”

Multistrain influenza protection induced by a nanoparticulate mucosal immunotherapeutic

“…Many previous attempts to use M2, 48,49 HA, 50 and NP proteins 51 to achieve broad-spectrum protection against influenza have been made. However, these studies have relied on the generation of " universal " antibodies that cross-react against diverse influenza strains -an approach that has yet to be proven practical in diverse populations.…”