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Bacterial protein could eliminate need for adjuvants in flu vaccines

Nanoparticles made of a protein carrying a flu antigen increased survival of mice infected with two strains of influenza

by Lakshmi Supriya, special to C&EN
June 28, 2021

Illustration shows a green BP26 protein with a red eight-member sequence of M2e proteins attached to the end. Sixteen protein units self-assemble into a barrel-shaped nanoparticle, with the red M2e protein sequences at the top and bottom.
Credit: ACS Nano
BP26 proteins (green) from the Brucella bacterium are modified with an antigen consisting of a sequence of eight M2e influenza virus proteins (red). Sixteen of the modified proteins self-assemble into a nanobarrel structure (right) that could be used in a vaccine.

Some commercial influenza vaccines contain adjuvants, components added to increase immune response and enhance the vaccines’ effectiveness. Although these adjuvants generally cause only mild side effects, if any, in rare cases they can trigger serious adverse effects such as inflammation and allergic reactions. Now, researchers report that a flu vaccine using a modified bacterial protein can stimulate a strong immune response without needing an adjuvant. Also, the vaccine candidate increased survival of mice infected with different flu viruses, opening up the possibility of using the protein in a universal flu vaccine, one that would not have to be reformulated each year to match the virus strains in circulation (ACS Nano 2021, DOI: 10.1021/acsnano.1c04078).

Flu vaccines use a molecule from the surface of the virus, or antigen, to elicit an immune response. But the antigen by itself may not be enough to generate adequate response, thus requiring the addition of an adjuvant. To better mimic how the flu virus stimulates the immune system, researchers have made nanoparticles with antigens attached to their surface.

“We searched pathogenic bacteria for a self-assembled protein nanoarchitecture that could serve as a new antigen-delivery vehicle,” says Sangyong Jon of the Korea Advanced Institute of Science and Technology (KAIST), who is a corresponding author of the new study. Previously, Ji-Joon Song of KAIST and colleagues reported that an outer membrane protein, BP26, from a Brucella bacterium can self-assemble into a barrel-like nanostructure made of 16 protein units (J. Mol. Biol. 2013, DOI: 10.1016/j.jmb.2013.01.015). The protein has also been found to stimulate a strong immune response in mice.

So, Jon, Song, and their team connected BP26 protein units to their chosen antigen, a flu virus protein called M2e. The units then assembled themselves into a nanobarrel structure with M2e on the surface. M2e is present in most types of flu viruses and is conserved, meaning it doesn’t mutate much, increasing the possibility of using it in a potential universal flu vaccine.

The team immunized mice with three doses of the nanobarrel particles and later infected the animals with an H1N1 influenza A strain. The mice had a 90% survival rate, whereas nonimmunized mice infected with H1N1 all died.

The team also tested the vaccine candidate against a different strain of influenza A (H1N1pdm09), one that caused a 2009 pandemic. Immunized mice had a survival rate of 75% whereas all the nonvaccinated mice died.

Adjuvants are needed when trying to use conserved regions of the flu virus to elicit an immune response, says Xavier Saelens of VIB-UGent Center for Medical Biotechnology, who studies flu viruses and was not involved in the study. “The approach with the nanocages is novel because it makes use of a very small VLP [virus-like particle].” Saelens adds that the researchers can produce the nanoparticles in Escherichia coli, a simple bacterium, “and thus, in principle, their vaccine is very cheap to produce.”


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