The pharmaceutical company Pfizer is working on a vaccine for respiratory syncytial virus (RSV) for newborns. Its effectiveness “in preventing severe RSV disease in newborns within the first three months of life was 81.8 percent. In the first six months of life it was 69.4 percent. The candidate vaccine was well tolerated. There were no safety concerns for either the vaccinated or their babies,” Pfizer said a few days ago communicated.
Study with 7,400 pregnant women
The vaccination concept is remarkable: the immunization of pregnant women is intended to provide protection against the viruses, which can lead to serious respiratory diseases, via the transfer of the resulting antibodies from the expectant mothers to the unborn child. This concept was tested in the now completed approval study. In this Matisse investigation (MATernal Immunization Study for Safety and Efficacy), around 7,400 pregnant women in 18 countries were vaccinated at random with a single dose of 120 micrograms of the vaccine or a placebo. This happened in the late second or third trimester of pregnancy. “The study was started in June 2020 and thus covered several waves of disease,” wrote now the Deutsches Ärzteblatt. Waves of RSV disease are typical for the colder seasons, often as early as the beginning of autumn.
Protein in two forms
The development of such RSV vaccines was preceded by many years of intensive research with, in one case, tragic incidents. Molecular biology made the crucial advance in the search for suitable antigens. Effectiveness and side effects depend on the form of the proteins used. In the search for the protein that could serve as an antigen for RSV vaccines, the RSV fusion protein (F) was identified a few years ago, which mediates the fusion of the viral envelope with the cell membrane during infection. In 2000, electron microscopic studies revealed an interesting detail: RSV-F exists in two forms, a pre-fusion structure and another post-fusion structure.
“The protein changes and refolds. As this occurs, the virus and cell membrane fuse,” Jason McLellan, a structural biologist at the University of Austin, Texas, told Science earlier this year. Spanish experts finally proved that the pre-fusion protein of RSV is best suited. The Pfizer candidate vaccine contains RSV pre-fusion proteins from two RS virus variants.
Fatal study 50 years ago
Catastrophic events with a candidate vaccine had happened in 1965. At that time, 31 babies were given a heat and formalin-inactivated inactivated vaccine as part of a study by the US National Institutes of Health (NIH). But 23 of the children between the ages of two and seven months were still infected, and 18 had to go to the hospital. Two of the children died. There was only one case of infection in a control group. Finally, it turned out that the vaccination with the then whole virus dead vaccine – the new vaccines only contain individual proteins – had apparently made the children more sensitive to the RS viruses. Heat and formalin inactivation resulted in remodeling of the F-protein into the post-fusion morphology. There was no immunological protection, and at the same time the vaccination led to a particularly severe course of the disease.
vaccine for the elderly
Such problems are now eliminated by using pre-fusion proteins in the new vaccines. Pfizer now intends to apply to the US Food and Drug Administration (FDA) for approval of its vaccine. At the same time, studies are being carried out with the vaccine in senior citizens. The British pharmaceutical company GlaxoSmithKline (GSK) also has one for this age group vaccine developed, which has proven itself in clinical studies and is currently being reviewed for approval by the European Medicines Agency (EMA). The vaccine should of course offer direct protection for adults, and for infants via the “detour” of their mothers.
“The annual RSV epidemics are particularly dangerous for children in their first year of life. The infants develop what is known as bronchiolitis, which can endanger an adequate supply of oxygen. In the winter months, there is therefore an increase in hospitalizations and intensive care,” said the German Medical Journal.
Premature babies and newborns are particularly at risk. According to the German Robert Koch Institute (RKI), around five percent of the cases of congenital heart defects are fatal.