Dr Peter Palese | Developing a Universal Flu Vaccine
About this episode
The influenza virus – commonly known as flu – is a serious public health concern. There are an estimated 1 billion cases of influenza each year, causing approximately 650,000 deaths globally.
Vaccination is the main way to protect people from influenza. This involves exposing a person to harmless versions or parts of the virus, which their immune system uses to create a ‘memory’, including antibodies. This memory allows a person’s immune system to mount a rapid response when exposed to the real virus in the future.
Current vaccines are only moderately effective in protecting people from the various strains of influenza. In addition, influenza viruses mutate over time, meaning that new vaccines need to be developed every year, to reflect changes in the genetic makeup of the virus. To remain protected, people need to receive the latest vaccine each year. Read More
Influenza virus particles have two key protein molecules on their surfaces: hemagglutinin and neuraminidase. Influenza viruses are classified into subtypes based on the combinations of hemagglutinin and neuraminidase they express.
Because hemagglutinin is the major surface protein, it has been a key target for vaccines. However, genetic mutations frequently occur that alter this protein molecule. These changes greatly impact the effectiveness of vaccines to protect against all circulating strains of influenza.
Dr Peter Palese, Dr Adolfo García-Sastre and Dr Florian Krammer from the Icahn School of Medicine at Mount Sinai in New York are leading experts in influenza biology and the development of vaccines. They are working to develop more effective and broadly protective influenza vaccines.
The team’s new vaccines aim to provide long-lasting protection from influenza, reduce the need to develop new vaccines every year, and offer protection from pandemic flu strains that are likely to emerge in the future.
One of the team’s vaccines is known as a chimeric hemagglutinin vaccine – or ‘cHA’. Although this vaccine still targets hemagglutinin, it does so in a clever way.
Hemagglutinin protein molecules are made up of a ‘stalk’, which is anchored to the surface of the influenza virus, and a ‘head’, which sits on top of the stalk. Most flu vaccines expose people to a version of the ‘head’ of hemagglutinin; however, this part of the molecule is far more likely to mutate over time, rendering vaccines ineffective.
Dr Palese and his colleagues decided to primarily target the ‘stalk’ of hemagglutinin, as this area doesn’t change as quickly as the ‘head’. They designed a series of vaccines using the same ‘stalk’ but different variations of the ‘head’. Using the same ‘stalk’ encourages the body to produce higher levels of antibodies to this component.
The researchers conducted a clinical trial in 65 healthy adults to evaluate the safety of their new vaccine, and its ability to generate an immune response. The results of the clinical trial showed that the new cHA vaccine is safe and highly effective.
The team, under the leadership of Dr Florian Krammer, also developed a new vaccine based on neuraminidase – the other key protein found on the surface of influenza viruses. Neuraminidase undergoes much fewer changes than hemagglutinin over time, making it a more stable vaccine target.
Their vaccine consists of multiple copies of the neuraminidase protein. By binding these protein molecules with a component from the measles virus vaccine, the team increased their vaccine’s stability and the immune response it generates. Through animal studies, the researchers found that their vaccine provides strong protection against illness and death caused by influenza.
The research conducted by Dr Palese, Dr Adolfo García-Sastre and Dr Florian Krammer is a major milestone in influenza science, and will revolutionize how we protect against the virus. With further work, the team’s new vaccines will undoubtedly save countless lives and prevent devastating pandemics in the future.
Original Article Reference
Summary of the papers: ‘A CpG 1018 adjuvanted neuraminidase vaccine provides robust protection from influenza virus challenge in mice’, in NPJ Vaccines, doi.org/10.1038/s41541-022-00486-w; ‘A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial’, in Nature Medicine, doi.org/10.1038/s41591-020-1118-7, ‘Universal influenza virus vaccines that target the conserved hemagglutinin stalk and conserved sites in the head domain’, in Journal of Infectious Diseases, doi.org/10.1093/infdis/jiy711.
Financial support for this research was provided by NIAID grants and contracts, the US Department of Defense, The Bill and Melinda Gates Foundation, and GlaxoSmithKline.
For further information, you can connect with Peter Palese at email@example.com
This work is licensed under a Creative Commons Attribution 4.0 International License.
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