Epitope-focused vaccine design against influenza A and B viruses

Abstract

The threat of influenza A and B variants via antigenic drift and emerging novel influenza A and B strains in the human population via antigenic shift has spurred research efforts to improve upon current seasonal influenza vaccines. In recent years, a wave of novel technological breakthroughs has lead to the identification of many broadly anti-influenza hemagglutinin (HA) monoclonal antibodies (mAbs) and the elucidation of the conserved epitopes recognized by these mAbs in both the head and the stem of HA as well as the mechanisms of inhibition. These discoveries along with an improved understanding of how the immune system responds to influenza infection and vaccination has spurred great efforts on stem-based cross-subtype ('universal') vaccine design as well as RBS-based HA subtype-specific vaccine design.

Structural Definition of a Unique Neutralization Epitope on the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein

“…Of note, such unique mechanism of action has not been reported for other viruses. Antibodies against the receptor binding site (RBS) of influenza virus and the CD4 binding site (CD4bs) of HIV type I (HIV-1) exert their neutralizing activities largely through direct competition with their respective receptors (Wu and Kong, 2016;Ren and Zhou, 2016). Perhaps the closest scenario to MERS-4-mediated inhibition is found in antibodies targeting the V3 region of the HIV-1 envelope where binding may capture or induce conformational changes that block the subsequent interaction between the V3 region and the co-receptor CCR5 or CXCR4.…”

Historical review on thymosin α1 in oncology: preclinical and clinical experiences

“…These antibodies bind to viral surface proteins that mediated virus entry or budding from host cells, leading to neutralization, opsonization, and/or complement fixation. CD4 + T helper cells are required for antibody responses during the induction, expansion, differentiation, and maturation of viral surface protein-specific B cells [16]. Vaccine efficacy (and effectiveness) is affected by various host factors, including age, genetic differences in immune responsiveness, history of infection and previous vaccination against influenza, gender, medical history, and health status.…”

“…Many strategies for developing a universal influenza vaccine are based on raising an immune response against influenza proteins that are highly conserved across all strains [11]. To overcome these drawbacks, attractive approaches are aiming to develop a universal influenza vaccine, based on conserved protein regions or peptides (both B-and T-cell epitopes in the same formulation), shared by all strains and which are able to induce cross-protective neutralizing immunity against conserved viral antigens [16]. The current challenge is to develop strategies that allow strong antibody responses to the HA stem region, the less immunogenic region of the HA molecule.…”

The Vestigial Esterase Domain of Haemagglutinin of H5N1 Avian Influenza A Virus: Antigenicity and Contribution to Viral Pathogenesis

“…Besides above, there is a third class of mAbs that can neutralise diverse strains within the same subtype but do not cross-react with other subtypes [9,10]. Interestingly, several mAbs in this class have been documented to bind to the vestigial esterase (VE) subdomain of HA of the H5N1 subtype and they have been shown to bind to multiple clades of H5N1 viruses [11][12][13][14][15].…”