03 May 2021

Less than a year after the new coronavirus had been discovered, the first vaccines were ready for use, developed in record time. How do the corona vaccines differ from vaccines against influenza? And what happens when the virus mutates?

Jorma Hinkula and Mohammad Azrahuddin discuss test results in the lab.Doctoral student Mohammad Azharuddin measures the amount of antibodies against the coronavirus. Photo credit Alfred RomboFor the past 80 years, essentially all influenza vaccines have been produced using the same method.Professor Jorma Hinkula.Professor Jorma Hinkula. Photo credit Magnus Johansson

“Billions of hen’s eggs are collected just before the influenza season and each one is infected with the influenza virus. Each egg will give a vaccine dose for one person. The pharmaceuticals industry has been using this method since the 1940s. It’s rather incredible that we haven’t progressed further”, says Jorma Hinkula, professor of molecule virology at in the Department of Biomedical and Clinical Sciences at Linköping University.

The corona pandemic has changed vaccine development. As the coronavirus SARS-CoV-2 spread around the globe, frenetic activity started in several laboratories throughout the world to develop effective, safe vaccines against the new virus.Jorma Hinkula and Mohammad Azrahuddin discuss test results in the lab.Doctoral student Mohammad Azharuddin and Jorma Hinkula measure the amount of antibodies against the coronavirus. Photo credit Alfred Rombo

“All variants of vaccine manufacture that you can imagine are used to produce vaccines against SARS-CoV-2. It’s just great! Over 300 vaccine variants are already being developed. Some of them have come far enough to have been tested in humans”, says Jorma Hinkula.

The four vaccines currently approved for use in Sweden use the same virus protein to stimulate a response in the immune system against SARS-CoV-2, namely the notorious spike protein, which gives the virus its easily recognisable appearance.

“The spike protein contains at least 17 different locations, known as epitopes, that antibodies from the immune system can bind to. It’s amazing luck and, to be honest slightly unbelievable, that this virus offers so many epitopes on a single protein”, says Jorma Hinkula.

What about mutations?

All viruses can mutate, which leads to changes in the proteins that our immune system has learnt to react to. If the changes are large, the immune system can no longer recognise the virus. The influenza virus is notorious for its rapid rate of mutation, and for exchanging genes with other influenza viruses, to create completely new combinations. Such new variants of the influenza virus caused several pandemics during the 20th century. Luckily, the coronavirus is much more stable.

“It’s unlikely that all 17 points of attack that the immune system can react against on the virus spike protein will be completely eliminated by mutations. And if it does happen, it should be a lot easier for vaccine manufacturers to modify the vaccines after mutations in the coronavirus. For RNA vaccines, researchers at Imperial College in London have said that it will only take two months from a mutant being discovered until the companies can start production of a vaccine variant in sufficient amounts for more than a million people”, says Jorma Hinkula.Yuming Zhang and Laura Sandners in the lab.Yuming Zhang and Laura Sandners analyse serum from patients with the SARS-CoV-2 virus (serum IgG and IgA anti-SARS-CoV-2 S1 Spike ELISA). They want to find out whether patients have developed IgG antibodies against the virus protein that contains many neutralising epitopes. Photo credit Alfred Rombo

One of the questions that everyone is asking is, of course, how long immunity against Covid-19 lasts. In an interdisciplinary collaboration, scientists are currently following people who have had Covid-19. They measure the amounts of protective antibody and calculate how long the protection lasts.

They will also look at whether the immunity after vaccination differs from that gained by people who have been infected by Covid-19. The research is a collaboration between Håkan Hanberger and Åse Östholm-Balkhed at the Infectious Diseases Clinic at Linköping University Hospital, and Maria Sunnerhagen and Daniel Aili at the Department of Physics, Chemistry and Biology at Linköping University.

“We will probably not be able to completely eliminate the coronavirus by vaccination, since it is present in animals. They can act as carriers and spread the virus to humans. We will have to accept that the virus will always be with us, and that we must have vaccines available for a long time”, says Jorma Hinkula.

Since a new vaccine against seasonal influenza is needed every year, scientists in Jorma Hinkula’s group are investigating the possibility of making a combination vaccine that protects against both influenza and coronavirus. In collaboration with researchers in the UK and other countries, they are working to develop a vaccine in which proteins from the influenza virus and SARS-CoV-2 are linked to the surface by extremely small particles of gold.

“The advantage of gold is that it is not absorbed by the cells in the body, but is eliminated. And further – it’s also extremely unusual to be severely allergic to gold, so it can be used by nearly everyone”, says Jorma Hinkula.

Translated by George Farrants

The article has also been published in the magazine Forskning & Utveckling 1/21 (in Swedish).


Vaccines based on a new technique

The Covid vaccines – how do they work?

When this article is published, four vaccines have been approved for use in Sweden. All four are based on a new technique in which the body’s cells are given instructions to produce one of the virus proteins for a short period.

Two of the vaccines, those from Moderna and Pfizer, are RNA vaccines. They contain a piece of the genetic material, messenger-RNA (mRNA), from the virus. The mRNA contains instructions for the manufacture of a protein that is unique to the new coronavirus. Cells in the body start to manufacture the virus protein rapidly – as soon as an hour or so after vaccination. Part of the protein is transported to the cell surface, where it is displayed to the various types of cell that make up our immune defence. The cells of the immune system react to this foreign protein and activate a defence. If the vaccinated person is subsequently infected by coronavirus, the immune system is prepared to rapidly combat it.

The vaccines from AstraZeneca and Janssen-Cilag function in a similar way. The difference is that the genetic material in this case is in the form of DNA, packaged into a modified adenovirus. The virus can penetrate human cells and deliver the genetic material, but it cannot multiply.

The RNA vaccines are sensitive and must be stored frozen until they are to be used. The DNA vaccines are not so fragile, and can be kept for long periods in a refrigerator.

Plates with 96 wells filled with fluid of different shades of orange.
The darker the colour, the greater the amount of antibody against the coronavirus spike protein. Alfred Rombo

Study the protection

Researchers at Linköping University measure the amounts of protective antibody and calculate how long the protection lasts. The darker the colour, the greater the amount of antibody against the coronavirus spike protein.

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