Pfizer has an RSV vaccine. What took so long?

Pfizer has an RSV vaccine. What took so long?

On top of COVID and the flu, we are dealing with another serious respiratory infection, respiratory syncytial virus (RSV). Disturbing difference from RSV: Babies and children under 2 are severely affected. Virus infection can cause inflammation of the lungs and airways, and in the worst case it causes pneumonia.

RSV is not new — it has been circulating seasonally for decades. USA see more than 58,000 hospitalization every year due to illness, which also affects children globally. But this year, RSV is particularly bad in the US, with positive cases averaging approx 7000 per week. The number of hospitalizations in October 2022 is double as they were in October 2021. Recently, a 6-year-old boy in Michigan died of an RSV infection.

Earlier this month, Pfizer released data from a phase 3 trial of an RSV vaccine in a press release. The research included 7,400 pregnant women and infants (pregnant women can synthesize antibodies and passively transfer them to the fetus via the placenta). The shot was found to be around 82 percent efficient in the prevention of severe respiratory tract infections in babies in the first three months of life. Pfizer plans to submit the trial results to the Food and Drug Administration by the end of this year.

An RSV vaccine would be welcome news for parents. But then again, RSV has been around for a while. What took so long?

The fact that children are the target population for the vaccine is a major challenge, says Julia Hurwitz, an infectious disease researcher at St. John’s Children’s Research Hospital. Jude in Memphis. She is working on the development of an intranasal RSV vaccine for infants, which is currently in phase I trials, and will also target human parainfluenza virus infection in children. Hurwitz explains that her team is moving very cautiously in testing the vaccine on humans — starting first with adults, then with older children, followed by younger children. “Adults can say, hey, I’m willing to try,” she explains. “I’m basically willing to be the guinea pig and make sure this thing works safely.” That’s what happened with the COVID-19 vaccine: a bunch of adults first agreed to try it, and then it was tested on children, after those trials were successful. But for any RSV vaccine, researchers will at some point need newborns as test subjects, Hurwitz explains. And when they test on babies, researchers just want to go very, very slowly.

All this was further complicated by the catastrophic RSV vaccine tragedy that occurred in 1966. vaccine with inactivated virus was injected into children in Washington, DC, in 1966. Later, 80 percent vaccinated children who were then infected with the virus were hospitalized. Two died. Vaccinated children passed up against the virus compared to children who were not vaccinated, Hurwitz explains.

Most scientists attribute this failure to formalin, the chemical used by scientists to inactivate the RSV virus in the vaccine. It is thought to have changed the structure of the virus used in the vaccine, and in turn the vaccine launched producing nothing but weak antibodies, which ultimately restore the children’s immune systems to their ability to fight the real virus.

In 2008, infectious disease pediatrician Fernando P. Polack suggested another possibility in a study conducted on laboratory animals: a type of white blood cell called an antibody-making B cell may not have had the necessary level of immune affinity to bind with the vaccine. Therefore, the antibodies failed to bind to the inactivated virus in the RSV vaccine and neutralize it, essentially leaving the body unprepared to neutralize—that is, fight—the actual virus. The failed neutralization not only allowed the unlimited replication of RSV that children acquired through infection, Polack’s theory suggests; it also opened the way for deposition RSV-antibody complexes in the lungs. This led to an exacerbated immune response, including inflammation, and caused increased respiratory disease in vaccinated children. Moreover, the vaccine was also ineffective, according to Polack’s study, because it did not stimulate a set of receptors, found on immune and non-immune body cells, that were responsible for recognizing invaders.

Because of this 1966 tragedy, “the RSV vaccine world has been extremely cautious because we don’t want to repeat that mistake,” Hurwitz says. As Hurwitz works on his RSV vaccine, the most important rule he adheres to is not to alter the structure of RSV. “Show the immune system exactly what RSV looks like so that the appropriate B cells bind the vaccine,” she says.

It’s easier to do now than it was in the 60s—Hurwitz points out that we’ve come a long way in vaccine design. We are now adept at using genetic material to develop vaccines, as was done with mRNA vaccines for COVID-19. This allows vaccine makers to give the immune system a small piece of the virus to train against—it looks just like the real thing, but it’s not the whole virus. Pfizer’s RSV vaccine uses one of the viral proteins that helps the virus fuse with cells.

Based on the results released by Pfizer, Hurwitz is hopeful and optimistic about the new vaccine’s effectiveness. “I don’t like watching the years go by while all these kids get sick,” she says. “We don’t want to wait more.”



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