Vaccination against RSV in pregnancy could protect children in future

Clinical trial shows: Vaccine is effective and tolerable

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Berlin, 06.04.2023

The respiratory syncytial virus (RSV) is a worldwide pathogen that can cause severe respiratory diseases. Especially for newborns and infants, an infection with RSV can be dangerous. In a large-scale international vaccination study with the participation of Charité – Universitätsmedizin Berlin and the London School of Hygiene and Tropical Medicine, the effectiveness of a first vaccine candidate has now been examined. Participants received the vaccine during pregnancy. As the researchers describe in the journal The New England Journal of Medicine*, up to 81 percent of the children were reliably protected against a severe course of the disease in their first six months of life.

In Germany, it is estimated that about 50 to 70 percent of children become infected with RSV during their first year of life. By the second birthday, almost every child has experienced an RSV infection. The disease usually starts with a mild cold, then spreads to the lower respiratory tract and lungs and can lead to acute breathing difficulties and shortness of breath. Globally, about 100,000 children under the age of five died from RSV infection in 2019 – about 97 per cent of them in low- and middle-income countries.

“RSV disease can so far only be treated symptomatically. In severe courses, oxygen administration is essential for survival, which in poorer countries often cannot be realised in time or to a sufficient extent,” says Prof. Dr. Beate Kampmann, Director of the Institute for International Health at Charité and Einstein Professor for Global Health. “We therefore urgently need vaccination in order to be able to effectively protect the most vulnerable group, namely children under six months of age, from severe courses of disease following RSV infection.”

An effective option is vaccination during pregnancy, as is already recommended against influenza, whooping cough or COVID-19. After the vaccination, the expectant mother forms antibodies which she passes on to the unborn child via the placenta. The child then has effective immune protection that lasts for the first few months of life.

Extensive vaccination study in 18 countries

A pharmaceutical company has now developed such a vaccine, which is administered during pregnancy, against RSV. The vaccine, called RSV-preF, has now been tested for tolerability and efficacy in an extensive international study conducted in 18 countries between 2020 and 2022. Prof. Kampmann played a key role in the study as part of her many years of research work at the Vaccine and Immunity Research Unit of the Medical Research Council (MRC) in The Gambia, part of the London School of Hygiene and Tropical Medicine (LSHTM).

In the phase III trial now underway, the vaccine was administered as an injection into the upper arm of 3,682 randomly selected study participants during the second or third trimester of pregnancy. A similarly sized comparison group received a placebo, i.e. an injection without vaccine. Neither the study participants nor the study leaders knew who received the vaccine and who received the placebo until the end of the study period. This is therefore a placebo-controlled, randomised, double-blind study that meets the highest quality standards.

After birth, the children were examined regularly for one to two years and if they showed signs of respiratory illness. They were tested for the RS virus and the severity of the disease was assessed according to a pre-specified study protocol.

Approval applied for RSV vaccine

“The results of the vaccination study are extremely positive,” says Prof. Kampmann. “In more than 80 percent of the children, the vaccination of the mother during pregnancy prevented a severe course of RSV disease in the first three months of life, and more than two thirds were still protected at the age of six months. The vaccination was also very well tolerated by the women.” The vaccine has been submitted for approval to the European and US drug authorities. The results of the trial are expected to be available later this year.

Nearly half of the participants in the trial were from the US, and 30 per cent of them are from low- or middle-income countries. In The Gambia, for example, Prof. Kampmann’s team recruited about 200 participants. “We were able to successfully use our platform for vaccination studies with pregnant women, which we had already established in Gambia, for the RSV vaccination study,” says Prof. Kampmann. The renowned expert in paediatric infectiology has been active in the West African country for more than a decade. Among other things, she has launched a programme for immunisation during pregnancy to combat whooping cough in children. The aim is to prevent diseases like this and reduce infant mortality.

“It is important to conduct vaccination studies in the countries where the vaccines will later be used,” says Prof. Kampmann. “Especially in socio-economically disadvantaged countries, people often suffer from chronic intestinal infections due to poor hygiene conditions. This can lead – as in the case of rotavirus vaccination – to a lower effectiveness of the vaccination. And there are co-diseases such as malaria or HIV that affect antibody transport across the placenta. All of this affects how well a vaccine ultimately works.” For national vaccination boards, it is also important that a vaccine has proven effective within its own region, so that it can be recommended later.

“The overall tolerability of the RSV vaccine was quite excellent among the study participants and the effectiveness in preventing severe RSV disease in infants was convincing. We thank the women for their participation and hope that the vaccine can be used soon and save many young lives.” Young lives in The Gambia and around the world, as the past 2022/23 season in particular brought home the consequences of RSV infections: In Germany alone, admissions of infants and young children to intensive care units had risen by up to 350 per cent, according to the Robert Koch Institute. A situation in which health care reached its limit at times.

*Kampmann B et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. NEJM, 2023 Apr 05. doi: 10.1056/NEJMoa2216480

About the study

The phase III clinical trial (Maternal Immunisation Study for Safety and Efficacy – MATISSE) was led and funded by the pharmaceutical company Pfizer. Prof Kampmann and her research team did not receive any personal fees for conducting the study.

Links:

Original publication

Institute of International Health

London School of Hygiene and Tropical Medicine (LSHTM)

IMPRINT – IMmunising PRegnant women and INfants network

MRC-The Gambia