Covid-19 mutations call for new vaccine design


An electron microscope image provided by the US National Institute of Allergy and Infectious Diseases showing SARS-CoV-2 virus particles emerging from cells cultured in a lab. Those spikes are prone to mutation, which can cause problems with Covid-19 vaccines. — AP

By now, most would be familiar with the graphical representation of the Covid-19 virus: a spherical structure with many protruding spikes. The spikes enable the virus to attach to our cells and enter them, causing infection. As such, they have become a popular target for vaccine developers.

The problem is that these protruding structures are also relatively less stable – ie, they are susceptible to changes through genetic mutation. We are now seeing reports of new Covid-19 virus variants with notable spike mutations and there are concerns that our immune system will not recognise the virus if these spikes change significantly enough – which would render current versions of vaccines ineffective.

Although studies conducted by some vaccine manufacturers claim their vaccines are likely to be effective against the new Covid-19 variants, it may only be a matter of time before the mutations are significant enough to require continuously updated versions of the vaccines (to keep up with the mutations).

Mutations will keep on happening and this may result in a situation akin to the annually-needed common flu jabs. With the way things are looking, it doesn’t look like vaccination will be a one-off affair.

But why build vaccines around the spikes when there could be other parts of the virus that are less susceptible to mutational changes and can also trigger an immune response? According to Dr Sarah Caddy, a veterinary surgeon and clinical research fellow in viral immunology from the University of Cambridge, our immune system recognises other parts of the virus too (albeit at varying degrees).

The spikes are made up of “S” proteins; the virus envelope comprises of “E” proteins; the membrane comprises of “M” proteins; and the nucleocapsid (proteins inside the virus associated with the viral genome) comprises of “N” proteins. Dr Caddy referenced a research article by McEwan and James in the Progress In Molecular Biology And Translational Science journal that points out that after a Covid-19 infection, the human body actually produces more N protein antibodies than spike protein antibodies. This is a strong indicator that another immunity mechanism could be utilised in vaccine design. Future vaccine designs should consider exploring a combination of spike and N codes or other parts of the virus that are less prone to significant mutations to provide potentially longer-lasting immunity.

All the leading vaccines right now – the mRNA-based vaccines from Pfizer-BioNTech, Moderna and Oxford-AstraZeneca as well as the adenovirus vector type from Russia’s Gamaleya Research Institute – code for information that allows our cells to produce viral spikes or proteins that form the spikes. The uncertainties surrounding virus mutation, however, will impact the vaccines’ effectiveness, duration of immunity retainment and potential long-term effects. As such, the Malaysian government may want to consider taking the the following actions:

> Ensure procurement deals include favourable provisions on effectiveness, safety, immunity retainment, and validity of the procured vaccines, and stagger purchase commitments with related milestones.

> Conduct a pilot run of the vaccine rollout using several types of vaccines. This pilot run should target smaller populations first but it is necessary to become familiarised with logistics and handling.

> Base the larger scale rollout on lessons learnt from the pilot stage. This first batch rollout may also be considered a phase to funnel future vaccine choices.

> Monitor the first batch rollout similarly to how a late stage clinical trial is monitored. Results from third-phase clinical trials of the vaccines mentioned earlier have shown to be promising. However, without a significantly longer-term study (especially on Malaysian demographics), potential long-term effects, immunity retainment and impact of virus mutations cannot be determined with certainty.

> Prepare to track, monitor, gather and analyse this big data. This must not be overlooked or underestimated. Given the overwhelmed healthcare infrastructure and highly occupied medical professionals and health workers, authorities must plan and execute this accordingly. If not, it would be a waste of valuable and potentially life-saving data.

> Monitor the viral genome sequence to detect mutations and correlate medical data from the first batch of vaccine rollout.

These recommendations can help the Malaysian authorities in pursuing data-driven decision-making to potentially narrow down the best option for the next batch of vaccines, if and when deemed necessary.

AMEEN KAMAL

Head of Science & Technology, Emir Research

Note: Emir Research is an independent think tank focused on strategic policy recommendations.

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