«Vaccine development continues as fast as COVID-19 spreads»

Many laboratories are working hard on the COVID-19 vaccine, and there are as many as 115 such projects around the world. Who will be first? – A scenario is possible that several different companies in different parts of the world will obtain approval for selling their version of the vaccine and these will be products based on different technologies. This is good news, there are many people willing to get vaccinated – explains Aleksandra Mościcka-Studzińska, coordinator of pharmacy and biotechnology at the National Center for Research and Development.

1. As many as 19 projects have joined the work on the COVID-115 vaccine, the work is very intensive and the procedures are as simplified as possible
2. It will be given to a very large number of people, we cannot risk that it will show rare side effects that we have overlooked – explains Aleksandra Mościcka-Studzińska
3. The main work is currently focused on technologies based on viral vectors, DNA, RNA and recombinant protein
4. Information about SARS-CoV-2 mutations is alarming. This poses a risk that the preparations that are being developed today may prove ineffective against the new strain in a dozen or so months. This is a challenge for scientists

Karolina Świdrak, MedTvoiLokony: Pharmaceutical laboratories, which are currently working on the SARS-CoV-2 virus vaccine, announce that it will be available next year (or earlier). How it’s possible? It took years to develop other vaccines, so why is this acceleration?

Aleksandra Mościcka-Studzińska, coordinator of the area of ​​pharmacy and biotechnology at the National Center for Research and Development: The speed of work is due to several factors. Research teams have intensified their efforts and report on round-the-clock work. Information on the basic knowledge of the pathogen is quickly exchanged. All over the world, administrative barriers to research are minimized and financial support is increased. It is also worth noting that some researchers use previous experiences with the SARS virus. This is possible because SARS-CoV-2 uses the same receptor to bind to human cells as SARS – the ACE2 enzyme. One might be tempted to say that the work on the vaccine is progressing in proportion to the speed with which COVID-19 has become a global problem.

Thinking about the above-standard acceleration of the work on the vaccine, we cannot, however, omit the stages important for the safety of the vaccine in the research. After all, it will be given to a very large number of people, so we cannot risk it showing rare side effects that we have overlooked by oversimplifying clinical trials.

How exactly – stage by stage – is vaccine development? What are animal and human clinical trials?

The first step is to define which pathogen is responsible for the disease. The main component of the vaccine candidate is then developed, i.e. natural or synthetic antigens are determined which are intended to elicit a response in the body to prevent disease. These antigens may include virus-like particles, weakened viruses, or substances derived from pathogens. The next step is preclinical studies using tissue or cell cultures and animal testing to assess the safety of a vaccine candidate and its ability to elicit a specific immune response. Animal studies cover specific species, and these experiments give scientists an idea of ​​the reactions they can expect in humans. Thanks to this, a safe dose is initially determined, which will be used in the next phase of the research, as well as a safe method of its administration. Scientists can also carry out provocation studies on animals, i.e. vaccinate animals and then try to infect them with the target pathogen.

Before the next step, it is necessary to submit documentation to the regulatory authority for approval of the clinical trial protocol. Its approval starts clinical trials, i.e. tests involving humans.

1. WHO report: 70 teams are working on a COVID-19 vaccine

Clinical trials consist of three phases. In the first phase, it is tested vaccine safety and determined the type and extent of the immune response caused by the vaccine. Tests are conducted with the participation of several dozen adults, they can also be so-called blind tests (i.e. some people can get a placebo). Sometimes, although rare, a provocation model is used to attempt to infect participants with the pathogen after the experimental group has been vaccinated. When the results of phase I are promising, it moves to phase II, during which the group of volunteers already consists of several hundred people. The purpose of this step is to test the safety of the vaccine, immunogenicity, proposed doses, immunization schedule, and method of administration of the vaccine. In order to validate the results, randomization is used (random allocation of volunteers to particular research groups), and one of the groups is administered a placebo.

The next stage is the third stage clinical trials and they are attended by thousands to tens of thousands of people. These tests are also randomized, including testing the experimental vaccine against a placebo, and the studies are double-blind (neither the volunteers nor the doctors administering the drug know if the person is being given the vaccine or the placebo). One of the Phase III goals is to evaluate the safety of vaccines in a large number of people. Some rare side effects may not appear in smaller study groups and so may not be detected in earlier phases. Additionally, in Phase III, the safety of administering the new vaccine with other commonly used vaccines is assessed.

Laboratories working on vaccines do it according to several paradigms (RNA, protein envelope, tobacco leaves). What is each of them? And how will these vaccines (if they come into existence) differ from each other?

A vaccine against the same virus may have a different composition, trigger the body’s defense mechanism by means of different antigens, and the production of its main component may proceed in different ways. And so, according to reports (TT Le et al., Nature Reviews Drug Discovery, April 9.04.2020, XNUMX) Work is currently underway on 115 vaccine candidates against COVID-19, among them there are preparations based on: attenuated virus (unable to cause disease), inactivated virus (killed), non-replicating virus vector, replicating virus vector, DNA i RNA (this type of vaccine is designed to produce the target antigen only in the human body), recombinant protein, peptide, virus-like particles (which, instead of the entire pathogen, trigger the body’s immune response). These biotechnological products require appropriate production methods, mostly based on cell cultures of various organisms. For example, one of the technology platforms being developed for the COVID-19 vaccine involves the multiplication of virus-like particles in the cells of a tobacco-related plant.

It seems that vaccines based on attenuated or inactivated virus will not play a significant role in the race for vaccine registration. The main work is currently focused on technologies based on viral vectors, DNA, RNA and recombinant protein.

Who will finish the work first and provide humanity with a ready-made vaccine?

We don’t know, we are watching this race and we know about five companies that have started clinical trials, most of them phase I trials. We also have one report from China that CanSino Biologics has started Phase II research after only three weeks of Phase I research. early summer “.

A possible scenario is that several different companies in different parts of the world will obtain approval for selling their version of the vaccine, and these will be products based on different technologies. Given the size of the population willing to be vaccinated, information about the multiple sources of the vaccine will be good news.

When can a ready-made vaccine be available for sale?

Caution should be exercised when reporting that the vaccine was completed extremely quickly. One can expect a shorter registration time for the vaccine, but reports that it will happen in a few weeks or months are greatly exaggerated.

1. A Polish woman leads a team working on a vaccine against coronavirus

Additionally, the information about SARS-CoV-2 mutations is disturbing. We are getting signals that a virus strain found in India has a different binding mechanism to human cells (S. Chen, South China Morning Post, 14.04.2020/XNUMX/XNUMX). This creates a risk that the preparations that are being created today may turn out in a dozen or so months … ineffective against the new strain. This is a challenge for scientists who have to answer the question of whether it is enough for us monovalent vaccine ie containing antigens of one strain, or polyvalent – containing antigens of several strains.

What is happening among Polish scientists regarding the work on the vaccine?

In Poland, the Medical Research Agency started the so-called own study entitled “Research on the SARS-CoV-2 virus vaccine and support for research work on the search for effective therapy”, which is carried out in partnership with Polish and international centers. At the National Center for Research and Development, we have launched a special grant competition dedicated to Polish entrepreneurs and scientists who intend to conduct research and development in the field of diagnosis, treatment and prevention of coronavirus. The budget of the Fast Track “Coronaviruses” competition is as much as PLN 200 million from European Funds. We are waiting for applications from May 6. Polish scientists have become involved in the fight against the coronavirus, we believe that such initiatives will provide them with additional support.

How will you relate to the population resistance theory in the context of the SARS-CoV-2 coronavirus? The media devotes a lot of attention to countries with much less restrictions than in Poland, in the hope of developing herd immunity. There are also voices saying that social isolation will prevent us, as a population, from acquiring such immunity.

This is not about the concept of “population immunity” itself, but about the speed of its acquisition and the total humanitarian cost of achieving it too quickly. We know that SARS-CoV-2 can stay active on surfaces for a long time, and that patients become infected before they develop symptoms. In addition, there is information that the virus replicates in the upper respiratory tract, so we are talking not only about the droplet path of infection, but also the airborne droplet. As a result, as long as there is no registered vaccine, regardless of the implemented social isolation, the number of people who come into contact with this virus and become ill will gradually increase.

The system of restrictions adopted by most countries is to reduce the transmission speed and is an attempt to at least slightly adjust it to the efficiency of the health care system in a given country. In this way, we can increase the chances of survival for people with the most severe course of the disease.

Unfortunately, mathematical models show that despite numerous limitations (e.g. SL van Elsland and R. O’Hare, Imperial College London News Site, 17.03.2020/XNUMX/XNUMX), the number of patients requiring hospitalization will be exceeded all over the world, who will be able to provide comprehensive help.

This should lead us to consider different options for isolation, taking into account economic factors, the potential of the health service in a given country, and even the lifestyle of a given nationality or population density. The very discussion about acquiring quick herd immunity is in fact a discussion about more frequent than necessary dilemmas, which patient should be helped and who should be denied it, and the ethicality of consciously leading to such situations.

An additional aspect that complicates the issue of population resistance is lack of knowledge about how long the body of a person who has had COVID-19 gains immunity. Without this information, we cannot be sure whether a large percentage of people with a documented history of COVID-19 is an effective protection of the population against the recurrence of the epidemic. On the other hand, the vaccine, when it is available, will allow to protect the population, in particular people from high-risk groups, in a way that is not burdened with ethical dilemmas. Only then will it be rational to refer to the concept of herd immunity.

Learn more about the vaccine development:

1. Coronavirus vaccine may be ready in the fall, Oxford researchers say
2. A Polish woman leads a team working on a vaccine against coronavirus
3. COVID-19 vaccine produced in tobacco leaves? An innovative solution
4. Americans are testing the SARS-CoV-2 coronavirus vaccine
5. Johnson & Johnson wants to start testing the vaccine in September. How is the work of other producers going?
6. Jennifer Haller has volunteered to test a COVID-19 vaccine. She told how it looks in practice
7. What is coronavirus incubation?

How do you rate the work on a drug for COVID-19? At the moment, the disease is treated symptomatically, but strong experiments are underway to see the efficacy of treating COVID-19 with existing drugs for other conditions. How do you forecast the development of this research? Which of these drugs is the most promising? Will (and when) one comprehensive drug for COVID-19 be invented?

WHO has launched a global SOLIDARITY study that tests the potential of several COVID-19 therapies focusing on: remdesivir, chloroquine and hydroxychloroquine, lopinavir with ritonavir and interferon-beta. Also of interest is the use of favipiravir, tested in China, which has been approved in Japan since 2014 for the treatment of influenza strains unresponsive to current antiviral drugs.

As with the vaccine, scientists go to great lengths to find a cure for COID-19 as quickly as possible. Due to the time taken by preclinical and clinical trials of completely new drugs, the search mainly revolves around products that are already partially known and have become natural candidates for further research. Meanwhile, we have the option of administering antibodies from the plasma of convalescents, but this method requires the willingness to cooperate of people who have successfully passed through the infection.

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Aleksandra Mościcka-Studzińska

Deputy Director of the Expert Management Department at the National Center for Research and Development, Coordinator of the Pharmacy and Biotechnology Area. A graduate of the Faculty of Chemical and Process Engineering at the Warsaw University of Technology (specialization in industrial biotechnology) and a graduate of Telford College in Edinburgh. She is a co-founder of the Foundation for Young Scientists. She participated in Polish and international research projects related to therapeutic systems and controlled drug administration. A graduate of the Academy of Program Managers – SKILLS, Foundation for Polish Science. From 2007, she was associated with the National Center for Research and Development, where she was responsible for international programs in the field of medicine, pharmacy and biotechnology, and was the Coordinator of the INNOMED sector program dedicated to innovative medicine.