The next experimental challenge posed in the fight against covid-19 consists of the deliberate administration of the SARS-CoV-2 virus to healthy volunteers who have been previously vaccinated. This is known as a “challenge trial.” Why does it arise now and what is it for exactly?
The global health emergency created by the pandemic has unleashed a race against time to obtain effective and safe vaccines against the virus. For this reason, since March the scientific community has been debating the possibility of carrying out provocation tests. That is, administering the pathogen to healthy volunteers previously vaccinated to verify the efficacy and safety of the vaccines and accelerate their development.
The idea of conducting this type of trial has been raised in countries such as the United Kingdom and the United States, where some COVID-19 vaccines are in advanced stages of phase III clinical trials. In these trials, thousands of healthy individuals voluntarily submit to the vaccine or a placebo. Subsequently, it is controlled if there are differences in the incidence of virus infection, viral load and the degree of clinical involvement between the two groups. However, the definitive proof of the efficacy of a vaccine is to verify that vaccinated people do not suffer from the disease after experimental exposure to the virus.
Scientific basis and potential of provocation tests
From a scientific and technical point of view, these types of provocation tests are not unheard of in the history of vaccine development. In fact, the invention of the first known vaccine, developed by Edward Jenner in the late 18th century, already included a challenge trial.
The English doctor deliberately injected the human pox virus into a child who had previously been given a preparation from the pustules of a cowpox-affected farmer. This is the reason why this procedure for obtaining immunity against infection has since been known as a “vaccine”.
Regarding the potential of these trials, in addition to the evident acceleration in the process of developing an efficient vaccine, with the health and social improvements that this entails, we must add that these types of trials can help to better understand this new virus and the how covid-19 develops.
However, in order to carry out these provocation studies with guarantees, a series of technical considerations should be taken into account to reduce the risks. These would include the recruitment of young healthy volunteers with a low risk of developing a severe form of the disease.
Volunteers would also be closely monitored, who would be isolated in a health environment where any complications they may present can be treated early and appropriately. In this sense, it must be taken into account that some previous studies carried out in experimental animals for the development of vaccines against other recent coronaviruses such as SARS-CoV-1 and MERS-CoV showed certain pathological effects induced by these vaccines, which were also more frequent in elderly subjects.
Precisely, the population most susceptible to developing a more serious form of covid-19 are people over 65 years of age, and therefore they would be the first candidates to receive the vaccine. This problem would not be solved with provocation tests, since they will only be carried out in young people.
Considerations and controversy about provocation trials
From a technical point of view, challenge trials are a potentially useful strategy for vaccine development. They can provide rapid proof of their effectiveness, especially when there are low rates of infection in the population and therefore less risk of exposure to the virus.
The reality is that the use of these tests for the development of the vaccine is accompanied by some controversy due to its bioethical and biosanitary implications.
This controversy comes from the fact of exposing the participating healthy volunteers to a significant clinical risk, by deliberately confronting them with an infection unknown until less than a year ago, which has no effective treatment. Infection that has shown the possibility of having serious consequences for the health of those affected in the medium and long term.
These medical considerations, as well as the current context, must be carefully considered before considering conducting these trials. So that a balance can be struck between what is ethically desirable and what is necessary from a technical point of view.
In relation to this, the WHO has recently published the ethical criteria that must be applied in this type of trial for the development of vaccines against covid-19. Criteria that allow risks to be minimized and to ensure that said trials conform to the highest scientific, ethical and clinical standards.
On the other hand, it should be noted that the use of these provocation tests was proposed several months ago, when the infection rate of covid-19 had been reduced after the confinement carried out in the different countries. The low rate of infection recorded at that time could jeopardize the proper development of clinical phase III trials, in which the vaccine has to be tested in a large number of volunteers.
The provocation strategy would compensate for the low infection rate and would allow a faster study of the clinical phases. But, as planned, these studies will not begin until early 2021. Date by which it is estimated that we are still in the second wave of the pandemic, with high rates of infections worldwide. This could lessen the urgency of performing these types of infection-provoking procedures.
Antonio J. Ruiz Alcaraz, Associate professor, University of Murcia; María Concepción Martínez-Esparza Alvargonzález, Associate Professor of Immunology, University of Murcia and Maria del Pilar García Peñarrubia, Professor of Immunology, University of Murcia
This article was originally published on The Conversation. Read the original.
