As an unusually large and early seasonal surge of RSV cases floods children’s hospitals across the country, pharmaceutical giant Pfizer offered a glimmer of hope Tuesday in the form of phase three clinical trial results.
The company’s experimental RSV vaccine, given to pregnant trial participants, was 82% effective in preventing serious RSV-related lower respiratory tract disease in the first three months of an infant’s life. It was 69% effective in the first six months, Pfizer said.
“We are thrilled with these data as this is the first-ever investigational vaccine that helps protect newborns against serious RSV-related respiratory illnesses from birth,” said Annaliesa Anderson, Chief Scientific Officer of Pfizer, in a statement. communicated.
The company said it expects to file for regulatory approval with the Food and Drug Administration by the end of the year, which could mean a vaccine could be available in time for the COVID-19 season. RSV next year.
The announcement is promising, but there are also reasons for caution. The company only published the first results in a press release, for one. The data will require more detailed external review. Pfizer also noted that the vaccine failed to meet the second of the trial’s two primary objectives, which was to meet pre-determined statistical criteria for efficacy against not severe RSV-related lower respiratory tract disease, although the company says some efficacy was clinically significant.
Still, there’s reason to be excited about Tuesday’s news, which follows decades of struggle by researchers trying to tackle RSV. This includes a disastrous vaccine trial in the 1960s, which caused the development of vaccinated children After of an RSV infection and resulted in the tragic deaths of two infants.
A virus often overlooked
It may seem newly famous, but RSV – or respiratory syncytial virus (sin-SISH-uhl) – is a common seasonal virus that has long posed a serious risk to infants and toddlers. Almost everyone is infected during childhood and most suffer only mild respiratory illness. But for a small fraction of children, especially those under the age of 5, it can turn deadly. RSV sends approximately 3.6 million people to hospital each year worldwide and kills more than 100,000 children under the age of 5 each year. Deaths occur most often in infants under 6 months and in children in low-income countries.
In the United States, RSV is one of the leading causes of hospitalizations for children under 5 years of age. A typical RSV season sends between 58,000 and 80,000 children under age 5 to hospital and kills between 100 and 300, according to Centers for Disease Control and Prevention estimates.
Researchers have been working for decades to prevent and treat RSV. But a dark cloud hung over the ground for years, halting progress. It was formed in the 1960s, when researchers began working on an RSV vaccine. The design of the experimental vaccine used a standard treatment of the time – heat and a formaldehyde (formalin) solution to inactivate the virus and “fix” or stabilize its proteins. Thus, the formalin-inactivated viral vaccine could present an entire virion to the immune system that was unable to infect cells, but had all of its antigenic components essentially frozen in place so that immune cells could learn to target key components.
But the vaccine was a tragic disaster. Not only did it fail to protect children against RSV in several clinical trials in 1966, but it also appeared to make children more vulnerable to severe RSV.
For example, in a small US trial, researchers gave infants aged 2 to 7 months a three-dose diet. Of 40 unvaccinated infants in a control group, 21 acquired RSV during a subsequent wave of infection in the community, and only one of the unvaccinated infants required hospitalization. Meanwhile, of 30 infants who received the experimental vaccine, 20 caught RSV, but 16 (80%) required hospitalization. Two of the children later died of bacterial pneumonia that developed after they were infected with RSV.
Over the decades that followed, researchers developed How? ‘Or’ What exactly the vaccine caused “enhanced respiratory disease” (ERD) syndrome in vaccinated children. First, the formalin-inactivated RSV vaccine stimulated weak antibodies that only weakly blocked and neutralized live virus. This helpless response led to a buildup of antibody-virus immune complexes which, in turn, activate exacerbating immune responses, including inflammation. The vaccine also stimulated T-cell responses that can cause exaggerated inflammation of the lungs upon subsequent RSV infection. All of this can set the stage for serious illnesses and complications, such as bacterial pneumonia.