CHICAGO (Reuters) - le farmaceutiche stanno lavorando il più rapidamente possibile per sviluppare un vaccino per combattere il coronavirus in rapida diffusione che ha infettato oltre 100.000 persone in tutto il mondo.
Dietro le quinte, gli scienziati e gli esperti medici sono preoccupati che velocizzare l'iter di approvazione di un vaccino potrebbe finire per peggiorare l'infezione in alcuni pazienti piuttosto che prevenirla.
Gli studi suggeriscono che i vaccini contro il coronavirus comportano il rischio di "potenziamento del vaccino", dove invece di proteggere dalle infezioni, il vaccino può effettivamente peggiorare la malattia quando una persona vaccinata viene infettata dal virus. Il meccanismo che causa tale rischio non è completamente compreso ed è uno dei blocchi che ha impedito lo sviluppo efficace di un vaccino contro il coronavirus.
Normalmente, i ricercatori impiegherebbero mesi per testare la possibilità di potenziamento del vaccino negli animali. Data l'urgenza di arginare la diffusione del nuovo coronavirus, alcuni produttori si stanno muovendo direttamente in test umani su piccola scala, senza attendere il completamento di tali test sugli animali.
"Capisco l'importanza di accelerare le tempistiche per i vaccini in generale, ma da tutto quello che so, questo non è il vaccino con cui farlo", ha dichiarato il Dott. Peter Hotez, preside della National School of Tropical Medicine del Baylor College of Medicine a Reuters.
Hotez ha lavorato allo sviluppo di un vaccino per la SARS (sindrome respiratoria acuta grave), il coronavirus alla base di un grave focolaio del 2003, e ha scoperto che alcuni animali vaccinati hanno sviluppato una malattia più grave rispetto agli animali non vaccinati quando sono stati esposti al virus.
"Esiste il rischio di potenziamento immunitario", ha affermato Hotez. "Il modo in cui riduci tale rischio è innanzitutto dimostrare che non si verifica negli animali da laboratorio."
Hotez ha testimoniato la scorsa settimana davanti al comitato della Camera degli Stati Uniti su scienza, spazio e tecnologia sulla necessità di finanziamenti per la ricerca sui vaccini. There is no vaccine left for any of the new coronaviruses that have caused outbreaks in the past 20 years.
At least for now, world experts have concluded that accelerated tests are a risk worth taking.
During a World Health Organization (WHO) meeting specifically convened in mid-February, designed to coordinate a global response to the new coronavirus, scientists representing government-funded research organizations and manufacturers around the world agreed that threat was so great that the vaccine would have to switch rapidly from human testing before animal testing is complete.
"If you want to get a vaccine as quickly as possible," former WHO deputy director-general, Marie-Paule Kieny, who chaired the meeting, told Reuters, "You have to balance this with the risk you put on a very limited number of people and do everything you can to mitigate the risk as much as possible. "
The conclusion of that meeting, which was not open to the media, was not officially publicized by the WHO. It does not reflect any official position adopted by WHO, a United Nations body whose job is to help shape global health policy.
Regulatory oversight of drug manufacturers and research is in the hands of national regulators. The most powerful of these, the United States Food and Drug Administration (FDA), has reported that it is in agreement with the consensus and will not stand in the way of accelerated testing programs.
"When we respond to an urgent public health situation such as the new coronavirus, we intend to exercise regulatory flexibility and consider all data related to a given vaccination platform," said FDA spokeswoman Stephanie Caccomo in a statement. The agency did not specifically comment on animal tests for vaccine enhancement.
Coronavirus vaccine developers are still required to conduct routine animal tests to make sure that the vaccine itself is non-toxic and can help the immune system respond to the virus.
About 20 coronavirus vaccine candidates are being developed by research institutes and manufacturers including Americans Johnson & Johnson and France's Sanofi SA. The US government has allocated over $ 3 billion for coronavirus treatments and vaccines.
The biotechnology company Moderna Inc, which works with the U.S.-funded National Institutes of Health (NIH), is closest to testing humans, announcing plans to start testing with 45 people in Seattle this month.
Testing for the specific risk of vaccine enhancement in animals will proceed simultaneously with human trials, NIH told Reuters, which said it should determine if it is safe to expose more people to the vaccine. Moderna did not respond to requests for comment.
The plan complies with WHO consent and FDA requirements, said Dr Emily Erbelding, director of the microbiology and infectious diseases division of the National Institute of Allergies and Infectious Diseases (NIAID), part of the NIH. The trial is expected to last 14 months, an NIH spokeswoman said.
Dr. Gregory Poland, a virologist and vaccine researcher at the Mayo Clinic in Rochester, Minnesota, expressed doubts about this approach. "This is important, but it must be done in a way that reassures scientists and the public that these (vaccines) are not only effective, but safe," he told Reuters.
Hotez said he was surprised that human tests were going on. "If there is an improvement in the immune system in laboratory animals vaccinated with the Modern vaccine, this is a sight," he said.
The American immunotherapy company Inovio Pharmaceuticals Inc, which is developing a coronavirus vaccine in collaboration with a Chinese company, also plans to launch human clinical trials on 30 U.S. volunteers in April instead of waiting for animal studies on vaccine enhancement.
"The community as a whole has evaluated this and said that we do not want to delay the clinical process. We have been encouraged to go to Phase 1 studies as quickly as possible," Inovio CEO Joseph Kim told Reuters.
The company plans to launch human security trials shortly thereafter in China and South Korea, two countries that have been hit hard by the virus. Kim said he expected to have an answer to the question about vaccine enhancement later this year.
The Moderna / NIH study is enrolling patients at the Kaiser Permanente Washington Health Research Institute in Seattle. The choice of location, made several weeks ago, could prove problematic.
To reduce the risk to volunteers, scientists from the WHO meeting recommended manufacturers to limit early clinical trials to small groups of healthy people and to take them to places where the virus is not spreading, according to Kieny, who now he works at the French research institute Inserm. This reduces the chances that people taking the vaccine may encounter the virus and trigger a more serious reaction.
Ever since the location was chosen, the Seattle metropolitan area has emerged as the epicenter of infections in the United States. Washington state reported 162 coronavirus infections and 22 deaths, out of a total of 755 infections and 26 deaths in the country as of Tuesday, according to a count from Johns Hopkins University.
However, Moderna and the NIH are planning to move forward.
"We think there is no reason to have to change sites. If you change it, there might be a community broadcast on another site in the next two weeks," said Erbelding. “Any risk of this for the participants is very small. It would be manageable as the process progresses. People are observed very, very carefully. "
Tragic experiences from other vaccines and previous work on coronaviruses have raised some warning flags for developers.
The best-known example occurred in a U.S. study in the 60s of a vaccine created by NIH and licensed to Pfizer Inc to fight the respiratory syncytial virus (RSV), which causes pneumonia in infants. The vast majority of children who received the vaccine developed a more serious disease and two children died. A more recent example occurred in the Philippines, where around 800.000 children were vaccinated with Sanofi's dengue vaccine, Dengvaxia. Only later did the company learn that it could increase the risk of more serious diseases in a small percentage of individuals.
Research, including that conducted by Hotez, has shown that coronaviruses in particular have the potential to produce this type of response. But testing the risk of vaccine enhancement takes time because it requires scientists to breed genetically modified mice to respond to the virus like humans. Work on these and other animal models has just begun in several laboratories around the world.
Modern, Inovio and many other vaccine developers are not waiting for this process to complete and are planning to launch human studies in record time for a virus discovered only in December.
Both Moderna and Inovio claim that their vaccines have a lower risk of vaccine potentiation because they are made using newer technology that focuses on specific genes on the external spike portion of the virus. The coronavirus vaccines that caused the vaccine to potentiate were generally made using an inactive version of the whole virus. Neither company has so far produced an authorized vaccine.
J&J said it is developing animal models to test vaccine enhancement and hopes to have a vaccine candidate ready for human testing in October. A Sanofi spokesperson said the company will look into this risk before testing the vaccine in clinical trials.
"People know how traumatic the RSV experience has been," said Dr. Johan Van Hoof, global head of Janssen Vaccines, J&J vaccination unit. "When you see signs in animals like this, we shouldn't ignore them."