For the first time in the world, newborns will receive study vaccine for syncytial virus created by Chilean scientists
Vaccine would be ready in 2025 and could become the first against RSV and the first generated in Chile. The immunizer will be evaluated in almost 300 children in Santiago and Puerto Montt, to measure its safety and capacity to induce an effective immune response to the virus.
According to studies, the Respiratory Syncytial Virus (RSV) is a major health burden, causing millions of hospitalizations in children under five years of age worldwide due to the acute lower respiratory tract infections it causes.
The Respiratory Virus Circulation Report of the Chilean Institute of Public Health (ISP), from week n°19 of 2022, shows that of the positive cases detected RSV was the most frequently detected virus (36.6%) that week in the country, and the most affected age group was 1 to 4 years old.
Another research in 2013, conducted by the Millennium Institute of Immunology and Immunotherapy (IMII), in conjunction with the Catholic University, showed that this virus, besides being the main cause of respiratory disease in infants worldwide, produces neurological alterations, such as seizures and ataxia, which can lead to impaired learning.
But although there are still no authorized vaccines available to prevent this virus despite decades of research, this reality could change in a short time thanks to the work of almost two decades of Alexis Kalergis, UC academic, director of the IMII and creator and developer of what could become the first vaccine against this virus in the world to be applied in newborns and the first one generated in Chile. His work is so advanced that in the second semester he will begin the second phase of his clinical study to test the vaccine.
If successful results are obtained and the vaccine moves on to phase 3 and the last phase of the clinical trial, it is expected that the vaccine could be used by the child population within three to four years (which is the time that research processes always take) "as long as the results are positive and the necessary funding is available," explains Kalergis.
In 2017, 24 adults participated in Phase 1 of the study that measured its safety in humans, results that, like those obtained in the preclinical studies "have shown that the vaccine is safe and immunogenic," adds the researcher.
Now, the research will focus on newborns, because they are the target population of this vaccine. Since the main goal of this inoculation is to train the immune system very early in life, so that when the person faces the virus, he or she will do so with a properly prepared immune system "and this vaccine will protect and prevent the disease", comments Kalerigis.
For pediatricians, the syncytial virus is the most important infection that is not currently protected by vaccine, and having adequate protection would avoid having an outbreak that every year generates full emergency rooms, great economic expense and family cost "and that generates recurrent obstructive bronchitis in children who have a genetic component for that", explains Dr. Katia Abarca, UC researcher responsible for the execution of the clinical trial.
Pablo Gonzalez, associate researcher of the IMII, UC academic, and part of the research team, says that this vaccine "is the only one against the respiratory syncytial virus directed to pediatric population from birth. Other approaches address the infant population that most likely has already been exposed to the virus, or the vaccination of pregnant women, which can only transfer to newborns a transitory immunity that quickly fades over time".
Phase 2 in newborns
Two studies were recently concluded in collaboration with Iowa State University, United States, which evaluated the Chilean vaccine in about 100 newborn cattle, and the results showed that there was no evidence of vaccine-enhanced disease after exposure to inoculation, "suggesting that the vaccine is safe for use in newborns," the study explained.
These results, and if the remaining permits from the ethics committees and the ISP are obtained, encourage the initiation in the second semester of this phase 2, which will be extended for more than a year, and will include an estimated population of 300 newborns from Santiago and Puerto Montt. The study seeks to continue measuring the safety of the immunizer and its ability to induce an effective immune response to the virus, so that it can protect children during winter outbreaks.
The current stage will focus specifically on newborns, since infants under one year of age are the population that is most infected and has the most complications, "therefore we need protection to be very early", emphasizes Dr. Loreto Twele, pediatric infectologist, head of the pediatric service of the Puerto Montt Hospital, professor at the U. San Sebastián, and who will be in charge of the clinical area of the study in the region.
In addition, the idea of this vaccine is not to wait until two, four or six months of age to inoculate the youngest children, nor do they seek to make major changes to the current immunization program.
The group to be studied must be healthy term newborns (over 37 weeks of gestation), and that both the mother and the father voluntarily accept to participate in the study, and exclusion criteria will be that the mother has a chronic disease such as HIV, and that she is born with some complication.
The benefits of participating in this research, according to Twele explains, is that the infants will receive the same vaccine against tuberculosis (BCG vaccine) that all newborns receive within the first 48 hours of life, but in this case it will be a recombinant vaccine, that is to say that it has the genetic material of RSV inserted, "and therefore, it will produce the protection against tuberculosis which is the reason why the BCG is given and also, it would generate antibodies that will protect the newborn against the respiratory syncytial virus".
As for the duration of the study, Susan Bueno, IMII researcher, UC academic and part of the research team, says that they expect that within six months from the start of the enrollment of the volunteers the first safety data will be available. "We believe that during the first year after the vaccinations have begun we will be able to have consolidated data on the effect of the vaccine in newborn children".
In the future, the vaccine could also be designed for the elderly population, who also suffer severe RSV infections, but "safety studies would have to be carried out in this population" since one cannot extrapolate the results of studies carried out in other age groups, says Katia Abarca.
"We are confident that our vaccine would be an excellent mechanism to speed up the immunological protection of the child population against this pathogen and that it could make a significant contribution to public health in our country," says Kalergis.
Recombinant vaccine
The vaccine to be used in the study is a recombinant vaccine based on the BCG (bacillus Calmette-Guérin) that is given to newborns to prevent tuberculosis disease.
A recombination that has already been tested in newborn animals and also in healthy humans in the phases of the previous clinical trial and in previous studies, "and in all of them it was shown that the vaccine does not produce RSV, does not produce pulmonary alterations, that it benefits people, that it generates antibodies and that it protects against infection," says Twele.
The pediatric infectious disease specialist also explains that today we only protect infants through monoclonal antibodies, "which are antibodies against RSV that we only give to newborns at risk, such as premature babies, those with heart disease, etc.". Therefore, making a recombination with a vaccine that is given from the first hours of life, "the benefit would be gigantic".
If everything goes well and the trials are successful, in the future we could think of replacing the normal BCG with the recombinant BCG, and thus in a single vaccine we could have protection against a bacterium and a virus".
That is why in the study, we want to maintain that protection (against tuberculosis) and also add protection against RSV", explains Abarca.
The results will be considered successful if it is proven that the vaccine is safe and induces a specific immune response against Respiratory Syncytial Virus. "Obtaining this data is critical to advance to clinical scientific phase 3″ which will determine efficacy, i.e., whether the vaccine prevents or decreases disease, says Bueno.
While the vaccine against RSV is not available, "we must maintain the measures to prevent infection, especially with children under 1 year of age" who are more susceptible to developing severe symptoms due to infection with RSV, reiterates the researcher.
What will the study consist of?
Before the clinical trial begins in the second semester, the researchers will contact pregnant mothers in different offices and medical centers of the participating hospitals and will tell them about the study in order to invite them to participate.
This phase 2 will consist of evaluating the newborns before, during and after the vaccines are administered. "Prior to vaccination, clinical and laboratory tests will be performed to rule out any underlying diseases that could affect the safety and immune response results," explains Susan Bueno.
"We are going to weigh them, measure them, take a blood sample to know that their immune system is adequate, then they will receive the vaccine, which will also protect them against tuberculosis, because the children will receive the BCG vaccine, only the recombinant one, and then we will follow them for 6 months.
The follow-up will be to see how the infants evolve, how many develop syncytial or any respiratory symptom, "and we will take some blood samples in the following months precisely to measure the amount of antibodies generated", adds the person in charge of the trial in Puerto Montt.
The evaluations will seek to measure both safety and immunity.
Safety will be measured through a very close follow-up of all the adverse events that the baby may present. For this purpose, we will start with a very rigorous training to parents and/or guardians, providing them with a booklet where they will have to register what is requested on a daily basis.
The immunity, which refers to how the person responds against the BCG component and the RSV component, will be measured with the blood samples, which will be in the smallest possible volume, which will not put the infants at risk.
Thus, the children will have a guaranteed medical follow-up for 6 months, in which any respiratory event will be evaluated by the doctors, blood tests will be performed periodically (just the necessary ones to measure the immunity and also to see the evolution of the patient), and it will be a benefit for the participants since "I will have a pediatric medical team that will be following me for six months and that is an important benefit", adds Twele.
This clinical study, "is a benefit for our population, therefore we are very proud that this type of trial is being carried out in Chile" and, in addition, the people after the Covid vaccines understand better and better what the clinical trials are about, concludes the specialist.
"Our hope is that the new vaccine will be as well tolerated as BCG, and that is what happened to us in the Phase 1 adult study, we had no differences", explains Abarca.
Private support
In order to carry out the studies for the vaccine against RSV, the researchers obtained the support of CORFO, and currently "we have the valuable support of the Angelini Group, who have assumed the commitment to allow the execution of the phase 2 scientific-clinical study for our vaccine", says Kalergis.
Roberto Angelini, president of Angelini Investments, commented on the motivation for making this contribution, "today, more than ever, we must support scientific research to address the great challenges facing humanity. For this reason, we are collaborating with Dr. Kalergis in the development of a vaccine against the syncytial virus, a serious disease that affects thousands of children and elderly people around the world. In this way, we hope to contribute to an important scientific breakthrough. It is a gamble that carries with it the hope of saving many lives".
In addition, Kalergis states that in the future, the collaboration of an international laboratory would be welcome to speed up the arrival of the product to the national and world population, "but we are open to several alternatives".
Regarding the Ministry of Health, the principal investigator points out that "before the pandemic we were in the process of reviewing the agreements and we have already held a meeting to update this agreement (with the Ministry)". Likewise, "I think it is important that Chilean science gives space to technologies that can be at the public service", he concludes.