Mirdad Kazanji: "An international solidarity has emerged for the knowledge of the virus. I hope the same will be true for the distribution of the vaccine"

Interview with Mirdad Kazanji, Director of the Institut Pasteur of French Guyana and member of IFGR

 

At a time when the Health Authorities of different countries are preparing to authorize the Covid-19 vaccines, we have once again asked Mirdad Kazanji* for a useful insight into the way they were developed and the challenges of this new phase of the fight against the global pandemic: the vaccination campaigns.

Vaccines typically require years of research and testing before reaching the clinic, but in 2020, scientists embarked on an unprecedended race to produce safe and effective coronavirus vaccines in record time.

The process started in January 2020, when the SARS-CoV-2 genome was completely deciphered. The first projects to develop a vaccine began immediately, with a phase of experimental trials in animals and then in humans, until the first results of phase 3 clinical trials proving the efficacy of certain vaccines were released in November. And today, Health Authorities in several countries, including Canada and the United States, have already given their approval to launch vaccination campaigns, some, such as Great-Britain, using emergency use authorization prior to official approval. China and Russia, meanwhile, have approved vaccines without waiting for the results of Phase 3 trials, which is considered by many experts to be a rushed and risky process.

 

Today, in my opinion, the only way to eradicate the epidemic is the vaccine. We have talked about herd immunity, but to reach it, 60% of the population would have to be affected by the virus and that would have an enormous human cost. Although the mortality rate[1] from Covid-19 remains low overall (around 0.5-1%), the risk of dying varies considerably depending on age, genetic heritage, access to care, socioeconomic status and general health conditions of individuals. Most importantly, to date, this virus has already caused more than 1.5 million deaths worldwide.

There was also a strong initial focus on treatment, with the belief that existing drugs for other types of viruses could be effective. But no in vivo treatment has proven to be effective and targeted against Covid-19. However, other new molecules are currently being evaluated.

Vaccine is the only immediate solution to reduce the spread of the virus and the severity of the infection. It must be well understood that the first vaccines on the market do not seem to prevent the transmission of the virus, i.e. the immunity induced by vaccination will not be sterilizing. Immunized individuals could continue to carry and potentially transmit the virus to others. On the other hand, it appears that the severity of the disease is lower after vaccination. The respect of protective measures will therefore have to be maintained!

Let’s keep hope because research is progressing very quickly: as of December 11, 2020, there are 57 vaccines in phase 1 and 2 clinical trials on humans, 15 vaccines are in phase 3 and 5 vaccines are currently in limited use after receiving the approval of Health Authorities in various countries. Finally, 85 vaccines are currently in the pre-clinical phase.

The first two main vaccines are those developed by the American laboratory Pfizer, in partnership with the German firm BioNTech (it has already been approved in the US and Canada), and Moderna, the Boston laboratory’s vaccine, which is in phase 3 and awaiting imminent U.S. and European approval. France plans to begin the vaccination campaign on January 4.

They use an innovative technology, messenger RNA, which had been used in rare cases of cancer control but never before for a vaccine. It is based on the use of a genetic code that will allow the cell to produce virus proteins that will themselves trigger an immune response. Researchers have succeeded in stabilizing the RNA by putting it in lipid particles that allow it to be used as a vaccine (to learn more about how messenger RNA vaccines work, read this article).

For these two vaccines, trials were conducted on volunteers of all ages during last summer to define their efficacy. For example, for the Moderna vaccine, of the 30,000 volunteers tested, 185 were infected with Covid-19 in the placebo group and 11 in the vaccine recipient group. This is what makes it possible to establish this rate of efficacy at 95%.

However, they present a major difficulty: their storage at high temperatures, -70°C for the Pfizer vaccine and -20°C for the Moderna vaccine (which can withstand a temperature of -4°C for several days). This means that logistics and the vaccination centers must be able to respect the cold chain, which will not be easy for all countries, especially the poorest, located in hot regions. Moreover, these two vaccines require two injections 3 weeks apart.

Another criticism concerns their efficacy and tolerance. The information transmitted by the pharmaceutical companies to the Health Authorities for the marketing application, indicates that these vaccines would cause few side effects. But scientists around the world are waiting for publications on their efficacy, duration of protection, toxicity and the immune response provoked in humans. These publications are expected shortly and will help to dispel doubts, both for the scientific community and the public.

The financial and material efforts made have been colossal, and precious time has been saved. For me, no step has been neglected and I believe that we must trust the researchers and the decision of the Health Authorities.

In addition, new clinical trials and the arrival of new vaccines as effective as the first two vaccines can be expected by June 2021. The interest is that they will use other technologies, such as recombinant vaccines (to learn more about the different types of vaccines, read a previous interview with Mirdad Kazanji). For example, the Institut Pasteur is working on a recombinant vaccine based on an attenuated measles virus strain (that is, researchers take the measles virus into which a portion of the SARS-CoV-2 virus has been inserted using molecular genetic engineering). Clinical trials are in Phase 3. SANOFI and GSK, for their part, have developed a vaccine based on recombinant proteins that has the same properties as the influenza vaccine. This vaccine is very promising because both laboratories have extensive experience in vaccination in general.

As can be seen, there are plenty of promising vaccines, but it is now important that these vaccines be accessible to all and free of charge to ensure the widest immunity. It is important that WHO or Gavi, the vaccine alliance, be involved in their distribution worldwide.

I remain confident. International solidarity has emerged for the knowledge of the virus and rapid progress has been made. I hope that the same will be true for the distribution of the vaccine.

 

For me, vigilance is still required: already because the arrival of vaccines in several countries does not mean that the pandemic will be stopped. The virus will continue to circulate because we won’t be able to vaccinate the whole world.

Then, we must be able to follow the mutations of this virus, which are inevitable as for any other RNA virus. Mutated versions of the virus have already been described, including N439K, which began circulating this summer in Scotland. It was then discovered several times in continental Europe and the United States independently. These mutations may have an impact on the transmissibility or virulence of the virus. However, the first good news is that CoV-2-SARS mutates half as fast as influenza viruses because the Spike protein attached to its surface, which opens the lock of our cells, appears to be quite stable. A recent study published in Nature also indicates that out of more than 12,000 mutations identified in the Covid-19 virus, none promote greater contagiousness. Nevertheless, it is essential to detect and describe these mutations, as they may require adaptation of vaccines or even the production of multi-strain vaccines to provide the broadest possible protection.

Third point of vigilance: monitoring vaccinated individuals. We have little experience with vaccine effects, only three to four months. Today, there is no certainty about how long vaccines will protect – although it will always be possible to make booster shots to reinforce immunity – nor about their tolerance. Follow-up of the first vaccinated cohorts will be essential to have a full understanding of potential side effects.

And, in conclusion, let’s not forget that we are not immune to a new coronavirus! Zoonoses – diseases or illnesses transmissible from animals to humans – represent 70% of human infectious diseases. Bats in particular are formidable virus reservoirs. The IPBES (the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services) estimated in a recent report that they are 1.7 million “undiscovered” viruses currently present in mammals and birds, of which 827,000 could potentially infect human beings (read more in our previous article about how pandemic risks can be controlled and prevented). Hence the importance of tackling the causes of the emergence of infectious phenomena rather than merely respond to them.

 

*Virologist, Mirdad Kazanji has been Director of the Institut Pasteur of French Guyana since 2014. He is a member of the Scientific Committee of the Territorial Collectivity of French Guyana. 

[1] This rate corresponds to the number of deaths in relation to the number of people infected.

• Interview written by Marie-Cécile Grisard, IFGR