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By Roger Highfield on

Coronavirus: How dead virus can save lives

A traditional kind of vaccine is being readied for the fight against the COVID-19 pandemic. Roger Highfield, Science Director, finds out about Europe’s first ‘inactivated virus’ vaccine.

As the number of people in the UK who have received their first coronavirus vaccine has passed the 15 million milestone, new COVID-19 vaccines are waiting in the wings.

In September 2020, the French company Valneva announced a partnership with the UK government to develop its inactivated COVID-19 vaccine, VLA2001.

Under the agreement, if the development of the vaccine is successful, Valneva will provide the UK with 60 million doses in the second half of 2021, with options over an additional 130 million doses until 2025.

I talked to Dr Juan Carlos Jaramillo, Chief Medical Officer of Valneva, which has its headquarters in Saint-Herblain, France.  His edited responses are shown below in italics.


We are developing our vaccine candidate in Europe based on inactivated virus (or killed vaccine), where the virus particles are grown in culture and then killed to destroy their disease-producing capacity.

This vaccine will be an add on, complementing the other vaccines that have already been approved, such as from Pfizer, Moderna and Oxford/AstraZeneca.

We’re extremely happy that these products have come to the market and we will be in a position to add more doses, notably for the UK Government and other regions of the world.

The first inactivated vaccines were developed in the late 19th century by Theobald Smith and Daniel Salmon at the U.S. Department of Agriculture and at the Pasteur Institute in France by Emile Roux and Charles Chamberland.

Inactivated vaccines contain a killed version of an organism that causes a disease which stimulates the body to create an antibody response. While many approved vaccines are based on the SARS-CoV-2 spike protein, which the coronavirus uses to invade human cells, the inactivated vaccine created by Valneva should trigger an immune response to a number of viral proteins.  As a result, an inactivated vaccine may be less vulnerable to mutations in the viruses’ spike protein which allow them to shrug off antibodies produced after vaccination or natural infection.


When it came to the clinical development program, it was very important that we used our current platform technology that we use to create inactivated vaccine.

We have a product that’s been on the market for quite a few years, which has shown to be safe, a vaccine called IXIARO which protects against Japanese encephalitis, a serious disease which is caused by the virus Flavivirus, which is closely related to Zika virus, dengue fever, yellow fever and West Nile virus.

We did a ‘plug and play’ of the COVID-19 into our Japanese encephalitis manufacturing and development to make our COVID-19 vaccine, which we call VLA 2001.

Our COVID-19 vaccine consists of inactivated whole virus particles of SARS-CoV-2, in combination with two substances, called adjuvants, that boost the immune response to make it more effective.

We began this work in late summer of last year and then we went into discussions with the UK government and of course knowing that we have the manufacturing facilities in Livingston, Scotland, there was a great interest in having the vaccine manufactured in the UK.

We went into an agreement with them and we are upscaling our UK manufacturing capacities, adding a new manufacturing building, an investment that will help with future potential outbreaks. 


We have a lot of experience in developing inactivated vaccines, where we use the whole virus and we inactivate it through a process that has been well tested and approved.

We made a start to the vaccine process in our labs in two locations, our Livingston facility and Vienna. In both places, we have what is called Biosafety Level Three laboratories to handle the virus in a safe, contained way, that has controlled airflow and are easy to clean.

We grow the virus in what are called Vero cells. We put the whole virus through different filtration processes in order to inactivate it through a purified, formalin-inactivation process and the final outcome is inactivated whole virus.

When it comes to VLA2001, we added adjuvants, our components are alum and CPG 1018, which we believe will make it more immunogenic and that generates a bigger immune response. We are also going to seek approval by the MHRA (Medicines and Healthcare products Regulatory Agency) and European Medical Agency.

An adjuvant is an ingredient used in some vaccines that helps create a stronger immune response, though by the same token they can cause more local reactions (such as redness, swelling, and tenderness at the injection site) and more systemic reactions (such as fever, chills and body aches) than non-adjuvanted vaccines.

Aluminium salts were initially used in the 1930s with diphtheria and tetanus vaccines after it was found they strengthened the body’s immune response.

Newer adjuvants have been developed to target specific components of the body’s immune response so that protection against disease is stronger and lasts longer. CPG 1018 is a recently-developed adjuvant used in a hepatitis vaccine,  consisting of cytosine phosphoguanine motifs, a synthetic form of DNA that mimics viral genetic material.


This is a two-dose vaccine, given within one month and injected into muscle (intra-muscular).  We are looking at standard cold chain storage, so our vaccine can be kept in a fridge between 2 to 8 degrees Celsius.


We do anticipate having to deal with new strains and that’s currently something that we are also testing with the other types of variants that are coming up, especially the South African variant, the Brazilian variant and of course the UK variant. We will, of course, probably see more in the future.

There was a lot of discussion of the new variants at a recent meeting of the New York Academy of Sciences, for example, and the impact on the efficacy of the currently approved vaccines. For example, the Pfizer and biotech Moderna, NovaVax show differences in efficacy when preventing disease from one strain compared with another.

The benefit of inactivated vaccines is that we can go into and look at a bivalent, trivalent or even quadrivalent vaccine – a mixture of two, three or four different inactivated virus variants, similar to what we already see in the influenza vaccine.

Our current focus is our phase one (safety) study that we started in mid-December before the new variants emerged. We are using the Wuhan variant and it’s the one in clinical testing at the moment.

We are studying how to deal with the variants in animal models and in future will be heavily looking into it because we do see that there’s going to be a need for different vaccines in order to address virus mutations.

But, of course, it would still have to go through various rigorous non-clinical and clinical studies.


We have finalised the first part of our phase 1/2 programme on 150 patients and so far from the review from the independent Data Safety Monitoring Board (DSMB), we have not seen any major safety concerns, which is expected from an inactivated vaccine due to the long history of development.

When it comes to studying efficacy, we do need to complete the second vaccination, take blood samples and look at the specific results such as immunogenicity and safety, for example, which will take until around April.

Once positive phase 1/2 results, we are currently looking at initiating a Phase 3 clinical study with approximately 4000 patients and are under discussions with the UK regulatory agency, the MHRA.  

We are trying to get the final results of the phase three trial by the second half of this year. There are no shortcuts and patient safety and science are the number one, not politics.


Every day that people have no access to a vaccine means more deaths will occur. I do believe that because of the pandemic situation, we need to be a bit flexible on how we approach standard clinical trials, and to think creatively and always keeping the patients at heart.

What is most important is making sure that there are open discussions and sharing of clinical data to make sure that we can optimize all the information that is being generated about the disease and the clinical results from the clinical trials.

What I see in the media, even among my own family members, are people asking if we can trust a vaccine that has been developed in less than 12 months when it usually takes 10 to 15 years to bring a vaccine to market.

This debate, about delaying the second dose, is also a topic in the US. From a scientific perspective, we need to be very diligent and conduct the appropriate trails before going that route.  

Again it boils down to the science and how we translate that science to the public. We need to make sure that the public trust the process of conducting the clinical studies, the results and most importantly, that we need to save as many lives as we can.

As you may already know, every day there is a lot of misinformation which then leads to anti-vaccination groups that argue against vaccination, as we saw in the UK with the MMR vaccination, for example. That’s something that I don’t want to see.


Very much the latter. 

What I do believe is that the UK approach shows they’re really thinking outside the box, which I commend. And of course, you’re always going to have critics – when you’re the first one to break through the wall, you’re the one who’s going to get more bruises. But I’m aware that they are being meticulous and diligent from every scientific angle to establish the best and most rational approach.

Sometimes the public might think this is just someone saying ‘let’s go for it’. But in reality, they are also getting a lot of feedback from well-renowned vaccinologists, those in charge of clinical trials, who do modelling and so on. So, I do believe it’s a prudent approach, and I’m supportive of this way of thinking.


The latest picture of how far the pandemic has spread can be seen on the Johns Hopkins Coronavirus Resource Center or Robert Koch-Institute.

You can check the number of UK COVID-19 lab-confirmed cases and deaths along with figures from the Office of National Statistics.

There is more information in my earlier blog posts (including in German by focusTerra, ETH Zürich, with additional information on Switzerland), from the UK Research and Innovation, UKRI, the EUUS Centers for Disease ControlWHO, on this COVID-19 portal and Our World in Data.