A revolutionary new vaccine in the battle against influenza

By Vinod RMT Balasubramaniam,

Monash University in Kuala Lumpur

Clinical trials of a universal influenza mRNA vaccine have begun in the US.

The US National Institute of Allergy and Infectious Diseases has started enrolling volunteers at Duke University in North Carolina to test its experimental mRNA-LNP vaccine against seasonal influenza, one of several universal influenza vaccine candidates now in the pipeline. Another clinical trial has begun at the US National Institutes of Health’s Clinical Centre in Maryland.

Influenza kills up to 650,000 people around the world each year.

Ninety-nine percent of deaths in children under five years of age in developing countries are due to influenza-related infections, according to the World Health Organization.

The current crop of influenza vaccines has limitations in effectively combating the billion cases of seasonal influenza each year as they provide immunity against only one specific existing strain or mutation. The propensity of flu viruses to mutate into new strains means vaccines must be continuously monitored and reformulated each year. 

But a universal influenza vaccine, using mRNA technology — which was used with success during the COVID pandemic —  has the potential to provide broader and longer-lasting immunity against diverse influenza strains. 

The technology allows for rapid development and deployment and offers versatility in targeting multiple regions of the influenza virus. 

New or mutated influenza variants are always a threat, particularly those originating from animal sources. Pandemics such as the Spanish flu of 1918, which killed 50 million people, and recent outbreaks of the avian influenza (“bird flu”) viruses underscore the persistent threat posed by influenza. 

It also underscores the urgent need for a universal influenza vaccine capable of safeguarding against all subtypes of the virus. 

In recent years, lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA (‘mRNA-LNP’) vaccines have emerged as a potent tool in combating influenza and other infectious diseases. 

These vaccines use mRNA created in a laboratory to teach our cells how to make a protein — or even just a piece of a protein — that triggers an immune response inside our bodies.

The limited efficacy of current vaccines can be attributed to their focus on only generating strain-specific antibodies against the influenza virus hemagglutinin (HA). This is a protein within the virus which causes infection.

To broaden protective immunity, novel vaccine strategies aim to elicit responses against more proteins (fragments of a virus). One promising avenue involves triggering T-cell responses. T-cells are a type of white blood cell and are part of the body’s immune system.

T-cell-mediated immunity not only eliminates infected cells but also correlates with improved outcomes in individuals affected by influenza. Animal studies have demonstrated the protective role of T-cells against various influenza virus strains.

These vaccines, exemplified by the successful development and global deployment of mRNA-LNP-based COVID-19 vaccines, elicit robust T-cell and antibody responses.  These vaccines also offer the advantage of rapid production and adaptation to target emerging viral variants. 

While several mRNA-LNP influenza vaccines are in development, most prioritise stimulating antibody responses and under-exploit the potential of T-cell immunity.

As shown by COVID-19, mRNA vaccines have demonstrated safety and efficacy in clinical trials for various infectious diseases. This instils confidence in the feasibility of developing a universal influenza mRNA vaccine that is safe and effective. 

Ongoing advances in mRNA technology, such as improved delivery systems and stabilisation methods, further enhance the prospects of creating a universal influenza vaccine that ticks all the boxes.

The mRNA vaccine technology offers several advantages, including rapid development, scalability, and precise design. Two categories of mRNA vaccines exist, conventional and self-amplifying and both are being explored for their potential to confer broad protection against influenza viruses.

Despite their promise, challenges remain in effectively delivering mRNA molecules into a vaccine due to their inherent instability. Overcoming these challenges is essential for the successful development of universal mRNA vaccines for influenza. 

Read more: Vaccine – the next step

Dr Vinod Balasubramaniam is Associate Professor (Molecular Virology) at the Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia.

Originally published under Creative Commons by 360info™.

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