Pfizer's vaccine to protect infants and older adults from the respiratory syncytialvirus (RSV) infection has been shown to be effective in late-stage clinical trials.
One company-funded study in 60-year-olds, whose results were published Wednesday by the New England Journal of Medicine, found that the vaccine did not prevent RSV-associated lower respir tract illness (which includes acute bronchitis or pneumonia) and it prevented RSV -associated acute respiratory illnesses. There are no safety concerns.
Another company trial was published on Wednesday with interim results. The RSV vaccine was administered to infants during late-stage pregnancy. It was shown to be effective against severe RSV infection. Safety concerns were not identified.
Pfizer seeks the approval of the US Food and Drug Administration for its RSV vaccine to older adults.
Pfizer also requested that the FDA approve its RSV vaccine for pregnant women to protect infants. According to Pfizer, the company expects to receive that decision by August.
FDA is also looking into a monoclonal anti-bodies treatment for children as young as 2 years.
The FDA's vaccine advisors voted for approval of RSV vaccine candidates from GlaxoSmithKline and Pfizer (GSK) in March.
If the FDA commissioner accepts the advisory committee, the vaccines could be the first in the world.
RSV vaccine: Why is it necessary?
RSV is a common disease. According to the US Centers for Disease Control and Prevention, most children will contract this highly contagious respiratory disease at some time before turning 2.
RSV is usually a mild infection, but it can cause serious complications, such as death or hospitalization, in some cases.
"When I began my residency thirty years ago, RSV season literally was a horrifying experience for us in pediatrics," said Claudia Hoyen (director of pediatric infection control at UH Rainbowbabies and Children’s Hospital in Cleveland), who was not part in the new studies.
She said that while providers would do everything possible to save babies in the NICU, many babies would be lost due to RSV.
Hoyen stated, "It was just... heartbreaking."
Monoclonal antibodies were introduced to protect the most vulnerable infants, making RSV more manageable. However, some of these infants are still at risk.
According to the National Institute of Allergy and Infectious Disease, RSV is a leading cause of death in the world.
Last year's particularly bad RSV season saw some hospitals for children have to put up tents in their parking lots in order to handle the overflow of patients. Hospitals are always busy, even during a typical RSV season.
Studies show that there are approximately 34 million episodes of RSV-associated lower pulmonary tract infections in children younger than 5 years old. About 10% of these children need to be admitted to the hospital. The virus is actually the number one cause of death in the United States. The number 1 reason that infants in the US need to be admitted to the hospital is because of the virus.
According to the National Foundation for Infectious Diseases, tens of thousands of older adults are admitted every year.
RSV can be very costly. Studies show that the US spends $709.6 million annually on infants suffering from RSV.
An inauspicious start
RSV is not a specific disease. A monoclonal antibody can be given to babies at higher risk for severe illness. However, it is difficult to administer and parents must visit the clinic at least once per month during RSV season. Doctors believe a vaccine would be extremely helpful but that trials have been stopped until recently.
A disastrous RSV vaccine campaign using an inactivated virus resulted in the hospitalization of 80% of the vaccinated children. They later contracted RSV. Only 5% of those who received a placebo were admitted to hospital.
As scientists investigated the cause of the problems, further trials were stopped for many years. The US government put in place additional safeguards to ensure that clinical trials were safe.
Ten years ago, a National Institutes of Health research team discovered the key mechanism of the virus. Scientists could use this knowledge to create vaccines that would detect the virus and trigger strong immunity.
The RSV vaccine race
Four companies were the only ones to have RSV vaccines for seniors during the last phases of clinical trials.
Johnson & Johnson's Janssen vaccine division was well advanced. The company, however, announced at the end March that it had abandoned its candidate.
J&J stated that the vaccine was lost as a result of the company's wider effort to make strategic decisions for its pipeline and research-and-development (R&D), investments in order to concentrate on medicines with the greatest benefit to patients.
Bavarian Nordic is the only company that has a focus on a vaccine to treat the elderly. It is expected to report its results by the middle of next year.
The numbers are the vaccines
The promising data provided by the companies was demonstrated when the FDA's independent advisors on vaccines voted to approve Pfizer's and GSK's senior vaccines.
According to a study funded by GSK, the RSV vaccine candidate for older adults prevented lower respiratory tract disease by 82.6% according to NEJM published in February. The shot prevented severe disease by being 94.1% effective.
Wednesday's results for Pfizer's vaccine against RSV-associated lower pulmonary tract illness in people aged 60 and over showed a 66.7% effectiveness against two or more symptoms or signs and an 85.7% vaccine efficacy to combat RSV-associated lower respiratory tract illness.
According to the study, there weren't enough cases of RSV-associated lower respiratory tract disease, which would require hospitalization or additional oxygen.
Dr. Ann Falsey suggested that one reason could be that trials were held during the Covid-19 pandemic when there weren’t as many RSV cases.
"Event rates were very low. They could not prove that it reduced hospitalizations. However, I believe that anything that prevents ARI, respiratory infections, and lowers the risk of infection will result in fewer hospitalizations. Although this makes perfect sense, they didn't prove that it was true, Falsey, a professor of medicine at University of Rochester School of Medicine, said Falsey. Falsey cares for RSV patients aged over 65 and also researches the disease. She was not part of the new research.
According to the study, the Pfizer vaccine was safe.
Guillain Barre syndrome was found among the 20,000 participants in the trial. This rare condition occurs when the immune system attacks nerves. It can occur one week after vaccination. According to company documents, the case was considered serious, but the fact that the patient had suffered a heart attack just days before the Guillain-Barre diagnosis may have contributed to the problem.
Miller-Fisher syndrome was also reported. This rare nerve disorder is thought to be a variant on Guillain Barre. The patient developed the disease 8 days after being vaccinated, but was able to recover in about a month.
During the discussion by independent FDA advisors about the vaccine, Dr. HanaEl Sahly, chair of that committee, stated that the incidence of the condition in these two cases was about 1 in 9000. This is significantly higher than the average rate in the general population.
Guillain Barre was also reported by a participant in the GSK study. This occurred nine days after the vaccine was administered. The patient spent six months in rehabilitation. FDA believes the case may be vaccine-related.
Doctors say that if the vaccines are approved it will be crucial to ensure their safety.
RSV vaccine for children under 5
Pfizer's interim results for its vaccine for infants showed that the candidate did not meet their criteria. This is likely due to the fact that the trial was conducted during the pandemic when RSV cases were less. However, research continues.
The editorial, written by Dr. Ruth Karron alongside the study published Wednesday, states that the effectiveness against severe RSV-associated lower pulmonary tract illness was 81.8% within the first 90 days and 69.4% in the second 180 days. It didn't prevent infections but it prevented them from getting worse.
Karron, a professor at Johns Hopkins Bloomberg School of Public Health in the Department of International Health and director of Center for Immunization Research at the Johns Hopkins Vaccine Initiative - was not involved with the new research and wondered if this age of RSV vaccine design could signal the end of large-scale RSV outbreaks.
A second study was published in NEJM Wednesday. It focused on nirsevimab. This monoclonal anti-RSV antibody made by AstraZeneca, Sanofi and is approved by the European Commission to prevent infants getting sick from RSV.
The study showed that 150 days after injection, the efficacy against RSV-associated lower pulmonary tract infection and hospitalization was 76.8%. And, 78.6% for very severe RSV-associated lower respiratory tract infection.
In the end, both babies born to term and those born late-preterm, one dose of RSV vaccine provided protection against hospitalization.
Hoyen believes that it will require a monoclonal anti-body treatment along with a vaccine to protect infants. Many pregnant women don't get vaccinated; at most, only 57% to 61% of pregnant people get shots to protect against the flu and tetanus-diphtheria-acellular pertussis, according to a 2020 study from the CDC.
Hoyen stated that although they try to vaccinate mothers while they are pregnant, overall, it is not a good job.
It is now up to the government how these vaccines and treatments should be used. Scientists will also monitor the duration of the vaccine's protection during the next RSV season.
Even with these caveats, RSV-positive health care professionals say it's amazing news.
"I am just beyond thrilled with these results. It's incredibly satisfying for someone who has been working in this field for over 30 years to see a vaccine available for both babies and older adults. Falsey stated, "It's fantastic."
Dr. William Schaffner is a Vanderbilt University Medical Center professor and medical director of The National Foundation for Infectious Diseases. He believes vaccines such as these can be a big help for public safety.
RSV is a huge problem, especially for children, but also for adults. RSV could cause as many illnesses as influenza, at least for a few years, according to Schaffner. These are promising potential advancements. They will be developed as many products mature and are brought before the Food and Drug Administration to be licensed this year or next. It will be an exciting time.