Pediatric RSV Vaccines: Why Are We Still Waiting?

Ask just about any practicing pediatrician about which vaccine he/she longs for, and you will usually hear the same answer: one protecting against RSV bronchiolitis.

The respiratory syncytial virus is the number one cause of pediatric respiratory hospitalizations in the US, averaging 58 000 per year and resulting in the death of 100-500 children under the age of 5 years every year. In comparison, influenza kills roughly 100 children a year. Only fairly recently has it been realized that adults older than age 65 years also suffer greatly from RSV with the CDC reporting 117 000 hospitalizations and 14 000 deaths yearly.

As a pediatrician who has had to admit infants to the hospital every winter over 40 years my conversations with anxious parents watching their child struggling to breath has not changed.

“What antibiotic or medicine are you going to give my child?” I am asked.

I have to tell them that many things have been tried (steroids, albuterol, ribavirin, nebulized hypertonic saline, immunoglobulins, montelukast, inhaled deoxyribonuclease, Heliox, and chest physiotherapy) but none have demonstrated any significant value. We give the baby supplemental oxygen and mechanical ventilation if needed and IV fluids if the rapid breathing interferes with oral intake. This supportive treatment hasn’t changed in 40 years.

The recent announcement by Pfizer of an injected RSV vaccine given to pregnant mothers with an 82% efficacy rate in children younger than 90 days and 69% efficacy through 6 months of age against hospitalization with RSV is welcome news. A caveat needs to be mentioned, however. The maternal transfer of antibodies to the fetus occurs predominantly in the last trimester and particularly in the last 4 weeks of gestation. I could not find any information of the vaccine’s efficacy in preterm infants, who also happen to be at highest risk of severe disease statistically. The Pfizer data has not yet been submitted to a peer-reviewed journal that hopefully will provide more information. I suspect we will still be giving prophylactic palivizumab (Synagis, RSV monoclonal antibody) to preterm infants even if this vaccine gains approval from the FDA.

Given the burden of RSV induced disease and the lack of therapeutic drugs, why has it taken so long to develop a vaccine to help infants?

Part of the answer dates back to an RSV vaccine trial done in the mid-1960s. Researchers took the RSV virus discovered only about 10 years earlier and inactivated it with formalin. Effective polio and flu vaccines were made with this technique, they postulated, so why not try it with RSV? No animal model was known at the time,so a human trial was done. (We do have one now in a specific mouse strain.) There were 441 children up to age 9 enrolled, about half received the RSV vaccine and half a parainfluenza vaccine as a control.