Stalking influenza by vaccination with pre-fusion headless HA mini-stem

Valkenburg, Sophie A.; Mallajosyula, Vamsee; Li, Olive T. W.; Chin, Alex W. H.; Carnell, George; Temperton, Nigel; Varadarajan, Raghavan; Poon, Leo L. M.

doi:10.1038/srep22666

Cited by 112 publications

(122 citation statements)

References 38 publications

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“…Besides the mini-HA and VRC headless HA constructs, other stem-based immunogens have been designed and reported 64, 65, 66, 67, 68, 69 . Another proposed approach to elicit heterologous and heterosubtypic immunity to the HA stem was the use of HA chimeras, where head domains from different subtypes are fused with a single stem domain, to direct the antibody response to the conserved stem region by sequential immunization with different chimeras 70, 71 .…”

Section: Design Of a More Universal Vaccinementioning

confidence: 99%

Structural insights into the design of novel anti-influenza therapies

Wilson

2018

Nat Struct Mol Biol

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A limited arsenal of therapies is available to tackle the emergence of a future influenza pandemic or even to effectively deal with the continual outbreaks of seasonal influenza. However, recent findings hold great promise for design of novel vaccines and therapeutics, including the possibility of more universal treatments. A major contribution to those advances comes from structural biology, in particular from the many studies on influenza hemagglutinin (HA), the major surface antigen. The HA primary function is to enable the virus to enter host cells, and structural work has revealed the various HA conformational forms generated during the entry process. Other studies have explored how human broadly neutralizing antibodies (bnAbs), designed proteins, peptides and small molecules, can inhibit and neutralize the virus. Here we review milestones in HA structural biology and how the recent insights from broadly neutralizing antibodies are leading to design of novel vaccines and therapeutics.

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Section: Design Of a More Universal Vaccinementioning

confidence: 99%

Structural insights into the design of novel anti-influenza therapies

Wilson

2018

Nat Struct Mol Biol

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“…Immunized mice exhibited high levels of cross-reactive antibodies against multiple HA subtypes and were protected against lethal challenge with A/PR/8/34 (H1N1)[32]. In a subsequent study, a similar HA2-based subunit vaccine was found to be highly immunogenic in mice conferring protection against lethal challenge with A/Hong Kong/68 (H3N2)[33]. Mallajosyula et al developed a headless HA stem vaccine based on the group 1 A/PR8 virus[34].…”

Section: Vaccine Approaches Targeting the Ha Stem Regionmentioning

confidence: 99%

Vaccine approaches conferring cross-protection against influenza viruses

Vemula

Sayedahmed

Sambhara

et al. 2017

Expert Review of Vaccines

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Introduction Annual vaccination is one of the most efficient and cost-effective strategies to prevent and control influenza epidemics. Most of currently available influenza vaccines are strong inducer of antibody responses against viral surface proteins, hemagglutinin (HA) and neuraminidase (NA), but are poor inducers of cell-mediated immune responses against conserved internal proteins. Moreover, due to the high variability of viral surface proteins because of antigenic drift or antigenic shift, many of the currently licensed vaccines confer little or no protection against drift or shift variants. Areas covered Next generation influenza vaccines that can induce humoral immune responses to receptor-binding epitopes as well as broadly neutralizing conserved epitopes, and cell-mediated immune responses against highly conserved internal proteins would be effective against variant viruses as well as a novel pandemic influenza until circulating strain-specific vaccines become available. Here we discuss vaccine approaches that have potential to provide broad spectrum protection against influenza viruses. Expert opinion Based on current progress in defining cross-protective influenza immunity, it seems that the development of a universal influenza vaccine is feasible. It would revolutionize the strategy for influenza pandemic preparedness, and significantly impact the shelf-life and protection efficacy of seasonal influenza vaccines.

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“…Bommakanti et al [49] reported that a headless H1 HA construct produced in E. coli elicited protection in mice against a heterologous H1 virus, but not heterosubtypic virus. Two follow up studies by the same group reported an improved headless H1 HA construct that elicited 30% cross-H3 protection in mice [50]; and a prefusion mini headless H5 HA construct that elicited the protection against lethal challenge of H5 and H1 (group 1) and H3 (group 2) viruses [51]. A recent study by Lu et al [52] reported a multi-step rational design approach that resulted in the headless HA displays correctly folded conserved conformational epitopes, but with no report on its in vivo efficacy.…”

Section: Stem-based Vaccine Design That Aims To Elicit Cross-subtype mentioning

confidence: 99%

Epitope-focused vaccine design against influenza A and B viruses

Ren

Zhou

2016

Current Opinion in Immunology

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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.

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Stalking influenza by vaccination with pre-fusion headless HA mini-stem

Cited by 112 publications

References 38 publications

Structural insights into the design of novel anti-influenza therapies

Structural insights into the design of novel anti-influenza therapies

Vaccine approaches conferring cross-protection against influenza viruses

Epitope-focused vaccine design against influenza A and B viruses

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