On top of COVID and flu, we are dealing with yet another tough respiratory bug, the respiratory syncytial virus (RSV). The upsetting difference with RSV: Babies and children younger than 2 are severely affected. An infection with the virus can cause the lungs and airways to inflame, and in the worst cases, it causes pneumonia.
RSV is not new—it’s circulated seasonally for decades. The US sees more than 58,000 hospitalizations each year due to the disease, which also affects children globally. But this year RSV is particularly bad in the U.S., with positive cases beginning to average at around 7,000 per week. The number of hospitalizations in October 2022 are double what they were in October 2021. Recently, a 6-year-old boy in Michigan died of an RSV infection.
Earlier this month, Pfizer reported data from a phase three trial of an RSV vaccine in a press release. The study included 7,400 pregnant people and infants (pregnant people can synthesize antibodies and passively transfer them to the fetus via placenta). It found that the shot is around 82 percent effective in preventing severe respiratory tract infections in babies for the first three months of life. Pfizer is planning to submit the results of the trial to the Food and Drug Administration by the end of this year.
An RSV vaccine would be welcome news for parents. But again, RSV has been around for a while. What took so long?
The fact that children are the target population for the vaccine is the major challenge, says Julia Hurwitz, an infectious disease researcher at St. Jude Children’s Research Hospital in Memphis. She’s working on developing an intranasal RSV vaccine for babies, which is currently in phase one trial, and will also target human parainfluenza virus infection in children. Hurwitz explains that her team is moving very cautiously in testing the vaccine on people—starting first with adults, then older children, followed by younger children. “The adults can say, hey, I’m willing to try,” she explains. “I’m willing to essentially be a guinea pig and make sure that this thing is working safely.” That’s what happened with the COVID-19 vaccine: A bunch of adults consented to trying it first, and then after those trials were successful, kids tested it. But for any RSV vaccine, researchers will at some point need newborns as test subjects, explains Hurwitz. And when testing on babies, researchers just want to move very, very slowly.
This is all made more complicated by a catastrophic RSV vaccine tragedy that happened in 1966. A vaccine with inactivated virus was injected to children in Washington, D.C., in 1966. Later, 80 percent of the vaccinated children who were then infected by the virus were hospitalized. Two died. Vaccinated children fared worse against the virus compared with children who were unvaccinated, explains Hurwitz.
Most scientists attribute this failure to the formalin, the chemical that scientists used to inactivate the RSV virus in the vaccine. The thinking is that it altered the structure of the virus that was used in the vaccine, and in turn the vaccine triggered the production of nothing but weak antibodies, which ultimately set the immune systems of the children back in their ability to fight the actual virus.
In 2008, an infectious disease pediatrician, Fernando P. Polack, suggested another possibility in a study conducted on lab animals: A type of white blood cell called the B cell that makes antibodies might have not had the required level of immunological affinity to bind with the vaccine. Therefore, the antibodies failed to bind with the inactivated virus in the RSV vaccine, and failed to neutralize it, basically leaving the body unprepared to neutralize—i.e., fight off—the actual virus. The failed neutralization not only allowed unrestricted replication of RSV the children acquired from infection, Polack’s theory suggests; it also paved the way for the deposition of RSV-antibody complexes in the lungs. This led to an exacerbated immune response, including inflammation, and caused enhanced respiratory disease in vaccinated children. Moreover, the vaccine was also ineffective, according to Polack’s study, because it didn’t stimulate a set of receptors, found on immune and nonimmune body cells, that were responsible for recognizing the invaders.
Because of this tragedy of 1966, “the RSV vaccine world has been extremely cautious because we don’t want to make that mistake again,” Hurwitz says. As Hurwitz works on her RSV vaccine, the most important rule she follows is to not change the structure of the RSV. “Show the immune system exactly what the RSV looks like so that the appropriate B cell binds the vaccine,” she says.
That’s easier to do now than it was in the ’60s—Hurwitz points out that we have come a long way in vaccine designing. We are now adept at using genetic material to develop vaccines, as was done with the mRNA vaccines for COVID-19. This allows vaccine makers to essentially give the immune system a little piece of the virus to practice against—it looks just like the real thing, but it’s not a whole virus. Pfizer’s RSV vaccine uses one of the virus’s proteins that helps the virus fuse with cells.
Based on the results that Pfizer has published, Hurwitz is very hopeful and optimistic about the new vaccine’s effectiveness. “I don’t like to see the years tick by with all these children getting ill,” she says. “We don’t want to wait any longer.”