[Source: PLoS One, full page: (LINK). Abstract, edited.]
Open Access / Peer-reviewed / Research Article
Globular Head-Displayed Conserved Influenza H1 Hemagglutinin Stalk Epitopes Confer Protection against Heterologous H1N1 Virus
Miriam Klausberger, Rupert Tscheliessnig, Silke Neff, Raffael Nachbagauer, Teddy John Wohlbold, Monika Wilde, Dieter Palmberger, Florian Krammer, Alois Jungbauer, Reingard Grabherr
PLOS / Published: April 18, 2016 / http://dx.doi.org/10.1371/journal.pone.0153579
Significant genetic variability in the head region of the influenza A hemagglutinin, the main target of current vaccines, makes it challenging to develop a long-lived seasonal influenza prophylaxis. Vaccines based on the conserved hemagglutinin stalk domain might provide broader cross-reactive immunity. However, this region of the hemagglutinin is immunosubdominant to the head region. Peptide-based vaccines have gained much interest as they allow the immune system to focus on relevant but less immunogenic epitopes. We developed a novel influenza A hemagglutinin-based display platform for H1 hemagglutinin stalk peptides that we identified in an epitope mapping assay using human immune sera and synthetic HA peptides. Flow cytometry and competition assays suggest that the identified stalk sequences do not recapitulate the epitopes of already described broadly neutralizing stalk antibodies. Vaccine constructs displaying 25-mer stalk sequences provided up to 75% protection from lethal heterologous virus challenge in BALB/c mice and induced antibody responses against the H1 hemagglutinin. The developed platform based on a vaccine antigen has the potential to be either used as stand-alone or as prime-vaccine in combination with conventional seasonal or pandemic vaccines for the amplification of stalk-based cross-reactive immunity in humans or as platform to evaluate the relevance of viral peptides/epitopes for protection against influenza virus infection.
Citation: Klausberger M, Tscheliessnig R, Neff S, Nachbagauer R, Wohlbold TJ, Wilde M, et al. (2016) Globular Head-Displayed Conserved Influenza H1 Hemagglutinin Stalk Epitopes Confer Protection against Heterologous H1N1 Virus. PLoS ONE 11(4): e0153579. doi:10.1371/journal.pone.0153579
Editor: Stephen J. Turner, Monash University, Australia, AUSTRALIA
Received: November 11, 2015; Accepted: March 31, 2016; Published: April 18, 2016
Copyright: © 2016 Klausberger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: MK and MW received funding from the Austrian Science Foundation FWF Doctoral program BioToP-Molecular Technology of Proteins W1224 and DP also was funded by the FWF (P 25092-B13). RT was funded by the Austrian Centre of Industrial Biotechnology (ACIB). ACIB is a non-profit research centre supported by the Federal Ministry of Economy, Family and Youth (BMWJF), the Federal Ministry of Traffic, Innovation and Technology (BMVIT), the Syrian Business Promotion Agency SFG, the Standortagentur Tirol and ZIT – Technology Agency of the City of Vienna through the COMET-Funding Program managed by the Austrian Research Promotion Agency FFG. FK was supported by an Erwin Schrödinger fellowship (J 3232) from the Austrian Science Fund. This work was partially supported by NIH (National Institutes of Health) program project grant 1P01AI097092-01A1 and PATH (Program for Appropriate Technology in Health). The Austrian Centre of Industrial Biotechnology provided support in the form of salaries for authors [RT], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.
Competing interests: Rupert Tscheliessnig was funded by and is employed by the Austrian Centre of Industrial Biotechnology. The Icahn School of Medicine at Mount Sinai together with the University of Natural Resources and Life Sciences has filed a patent on the mentioned display system for influenza epitopes (influenza virus vaccines and uses thereof; application no. 62180405). There are no further patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.
Keywords: Research; Abstracts; H1N1; Seasonal Influenza; Pandemic Influenza; Vaccines.