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Chimeric Vaccine Displays Broad Immune Responses against Multiple Influenza Strains
A novel chimeric influenza vaccine has been developed which has demonstrated strong cross-protective immune responses against various human and avian influenza viruses and subtypes in animal models.

A group led by Professor Wong Chi-Huey has developed a chimeric vaccine based on the most common avian influenza H5 and human influenza H1 sequences. The study, published recently in PNAS, demonstrated strong cross-protective immune responses against various human and avian influenza viruses and subtypes in animal models.

Influenza pandemics have presented significant threats to public health, with zoonotic viruses being a particular concern. The 2009 H1N1 swine flu epidemic had wide-ranging impacts, and the ongoing circulation of the highly pathogenic avian influenza strains H5N1, H5N2, and H7N9 in poultry are a significant concern as they may mutate and increase their transmissibility in humans.

While vaccinations are the most effective method for protecting people from becoming infected by influenza viruses, they can be rendered ineffective. Traditional flu vaccines target the head of hemagglutinin (HA), a protein found on the surface of influenza viruses which is integral to their infectivity. The vaccines work by preventing the globular head from binding to human cells. However, the HA head can mutate, making it hard to keep developing new vaccines in time, and the antibodies induced by a particular subtype are often not effective at neutralizing other strains and subtypes. Because of this, major efforts have been made towards developing a universal influenza vaccine to overcome these problems.

The HA protein has seven amino acids with abundant glycans attached. Previous influenza vaccines were derived from the HA of the H1N1 strain with glycans trimmed to a monosaccharide per site. In order to increase the strength and coverage of the vaccine, Professor Wong’s team used an innovative approach whereby they tested a variety of HA proteins from different subtypes of type A influenza viruses, combining the heads and stems from different strains to create a manmade HA protein, dubbed chimeric HA (cHA).

The study’s first author, Dr Liao Hsin-Yu, found that combining the head of H5 (avian influenza) and the stem of H1 (human influenza) produced the strongest immune responses from CD4+ and CD8+ T-cells.

She then trimmed the glycans on the cHA vaccine to the monoglycosylated glycoform (cHAmg) with only GlcNAc on each glycosite. This cHAmg vaccine was able to induce more stem-specific neutralizing antibodies with higher antibody-dependent cellular cytotoxicity (ADCC) and increased the killing activities of T-cells.

This vaccine was effective against a total of 6 subtypes of influenza in animal models and 10 subtypes in in-vitro experiments. It also demonstrated stronger cross-protection activity against H1, H3, and H7 strains and subtypes. Additionally, when it was combined with a glycolipid adjuvant, the vaccine’s efficacy was enhanced, with more IFN-γ, IL-4 and CD8+ memory T cells produced.

The researchers believe the same strategy could be applied to other viruses in similar scenarios, with hopes that a universal vaccine could be developed against SARS-CoV-2 and its variants.


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