Designing a reoriented H5 hemagglutinin to generate stem-directed, heterosubtypic immunity to influenza A viruses
Human infections with the highly pathogenic avian influenza viruses highlight the risk of novel pandemics, against which seasonal vaccines provide limited cross-protection. Whereas antibody responses to current vaccine candidates are typically biased toward the immunodominant and variable head region of hemagglutinin (HA), the stem region of HA is highly conserved and targeted by broadly…
Influenza A viruses pose a significant threat of emerging pandemics, with seasonal vaccines offering limited cross-protection. While antibodies produced by current vaccines often target the variable head region of hemagglutinin (HA), the highly conserved stem region of HA is targeted by broadly neutralizing antibodies. Researchers have developed a reoriented H5 HA (reoH5HAPhe) derived from A/Vietnam/1203/2004, which is displayed on alum as a vaccine candidate to induce stem-directed antibody responses for potential cross-protection.
In their study, they found that a single immunization with reoH5HAPhe provided protection against a lethal heterologous H5N1 challenge in naive mice. Furthermore, boosting with reoH5HAPhe conferred complete heterologous protection in mice previously immunized with seasonal vaccines. The stem-directed response elicited by reoH5HAPhe also offered protection against heterosubtypic H1N1 challenge in both naive and previously immunized mice.
Through electron microscopy polyclonal epitope mapping, the researchers discovered that reoH5HAPhe stimulated antibodies that targeted the central stem and anchor epitopes on heterologous H5 and H1 HAs, as well as antibodies against the (H5) vestigial esterase or (H1) lateral patch epitopes. Despite exhibiting limited cross-neutralizing activity, the increased stem-directed responses with balanced IgG1 and IgG2 subclasses led to reduced viral replication and improved survival.
The findings underscore the potential of antigen reorientation as an effective strategy for designing vaccines that can withstand viral mutations, and demonstrate the promising prospects of reoH5HAPhe as a pandemic influenza vaccine candidate capable of conferring immunity against both emerging and seasonal influenza viruses.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
