Abstract
Inaccuracies in prediction of circulating viral strain genotypes and the possibility of novel reassortants causing a pandemic outbreak necessitate the development of an anti-influenza vaccine with increased breadth of protection and potential for rapid production and deployment. The hemagglutinin (HA) stem is a promising target for universal influenza vaccine as stem-specific antibodies have the potential to be broadly cross-reactive towards different HA subtypes. Here, we report the design of a bacterially expressed polypeptide that mimics a H5 HA stem by protein minimization to focus the antibody response towards the HA stem. The HA mini-stem folds as a trimer mimicking the HA prefusion conformation. It is resistant to thermal/chemical stress, and it binds to conformation-specific, HA stem-directed broadly neutralizing antibodies with high affinity. Mice vaccinated with the group 1 HA mini-stems are protected from morbidity and mortality against lethal challenge by both group 1 (H5 and H1) and group 2 (H3) influenza viruses, the first report of cross-group protection. Passive transfer of immune serum demonstrates the protection is mediated by stem-specific antibodies. Furthermore, antibodies indudced by these HA stems have broad HA reactivity, yet they do not have antibody-dependent enhancement activity.
Highlights
Humoral responses against the stem domain post infection or vaccination are weak relative to those against the head domain
In this study, using our newly developed H5-mini stem polypeptide and our previously reported H1-mini stem as immunogens[12], we describe the use of a group 1 HA mini-stem to induce protection against both group 1 and group 2 viruses
We developed and tested the protective efficacy of a novel H5-based HA stem immunogen designed from influenza A H5N1 (VN/04: A/Viet Nam/1203/04) (GenBank Accession: AAW80717.1) virus
Summary
Humoral responses against the stem domain post infection or vaccination are weak relative to those against the head domain. We characterized our previously designed H1 mini-stem (PR/34: A/PR/8/34)[12] in a mouse model against heterologous influenza virus challenge, and evaluated the vaccine mediated antibody responses.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.