RSV infection vaccination recommendation for pregnant women

Every year in France, around 30% of infants under two years are affected by bronchiolitis, and 2 to 3% of infants under one year are hospitalised for a severe form. The epidemic generally starts mid-November, peaks in December, and finishes once winter comes to an end.

The Abrysvo vaccine developed by the firm Pfizer was granted a European Marketing Authorisation on 23 August 2023 for passive protection against lower respiratory tract illness caused by respiratory syncytial virus (RSV) in infants from birth to 6 months of age following active maternal immunisation during pregnancy.

The French Ministry of Health (DGS) submitted a referral to the HAS on 4 May 2023 with a view to assessing the relevance of incorporating this new vaccine in the RSV infection prevention strategy.

Who are the targets of these recommendations?

Public authorities

What are the objectives of this recommendation? 

The objective of this report is to assess the relevance of incorporating vaccination of pregnant women with the Abrysvo vaccine in the RSV infection prevention strategy for infants.

 Elements taken into account for the assessment

To draw up these recommendations, the HAS took into consideration:

• the clinical expression and epidemiological impact of RSV in infants;
• the lack of long-term immunity after natural infection and the lack of correlate of protection;
• RSV circulation mechanisms and the disruption of RSV epidemiology since the emergence of COVID-19;
• medical RSV infection management methods, limited to supportive care given the lack of specific therapeutic options;
• the passive immunisation campaign with monoclonal antibodies (nirsevimab, Beyfortus) launched in September 2023 and the acceptability data available;
• the characteristics of the Abrysvo vaccine and the data available in respect of efficacy, immunogenicity, safety and co-administration;
• the discontinuation of the clinical trial of the Arexy vaccine due to premature birth risks;
• the lack of post-marketing monitoring data in respect of this vaccine;
• the cumulative real-line impact and efficacy data of Beyfortus since the first passive immunisation campaigns were launched for infants in several countries;
• the lack of data to date relating to the risk of emergence of virus mutations associated with the use of monoclonal antibodies;
• international recommendations and the findings of the medico-economic studies available;
• the different possible scenarios for the vaccination period;
• the position of the members of the work group and the experts heard;
• the results of the public consultation;

Main conclusions of the recommendation

After its assessment, the HAS recommends RSV vaccination for pregnant women in order to reduce the burden associated with RSV infections in infants. It deems that the Abrysvo vaccine can be used within the scope of this vaccination strategy. However, pending additional pharmacovigilance data and in order to limit the consequences in view of a potential excess risk of premature births (non-significant for this vaccine, but resulting in discontinued development of a competitor vaccine), and in view of the lack of vaccine efficacy data for premature newborns, the HAS recommends, as a precaution, that the vaccine be administered only between 32 and 36 weeks of gestation.

Furthermore, based on current knowledge, the HAS specifies that maternal vaccination and passive immunisation with monoclonal antibodies are two alternative strategies. The HAS recommends that both RSV infection prevention strategies be presented and explained to future parents during pregnancy to allow them to make an informed decision as to the protection of the infant, and deems that it is necessary to develop information materials tailored to future parents and the different healthcare professionals involved in this vaccination (general practitioners, midwives, paediatricians, pharmacists, gynaecologists-obstetricians, nurses, emergency physicians, resuscitation specialists). Nevertheless, in cases where pregnant women have not been vaccinated or where vaccination is probably not effective (premature newborns, interval of less than 14 days between vaccination and birth), the HAS advises boosting with passive immunisation with monoclonal antibodies. In the absence of efficacy and immunogenicity data for immunocompromised women, the HAS recommends preferentially administering monoclonal antibodies to the infant.

In view Of the seasonal nature of RSV and efficacy data against severe forms demonstrating protection for the first six months postpartum, and in order to improve uptake and choice among families, the HAS recommends that the vaccination campaign be concomitant with the Beyfortus immunisation campaign, either before the start of the epidemic period and until the end of this period (from September to January for Metropolitan France). In order to optimise involvement and acceptability among healthcare professionals and parents, the HAS recommends accessibility to both medicinal products (vaccine and monoclonal antibody) in maternity hospitals.

The HAS specifies that the Abrysvo vaccine can be administered at the same time as an influenza or COVID-19 vaccine and notes that, in accordance with its MA, a minimum interval of two weeks is recommended between administration of diphtheria-tetanus-acellular pertussis (dTca) vaccine and administration of Abrysvo.

In the absence of data regarding the safety and efficacy of an additional dose of vaccine in the context of a successive pregnancy, the HAS has not delivered any opinion on the relevance of revaccination during subsequent pregnancies for a pregnant woman previously vaccinated during a prior pregnancy. Pending these data, and given the lowering of RSV neutralising antibody titres in pregnant women over time, the HAS recommends preferring passive immunisation of the newborn infant in the event of another pregnancy after a first vaccination.

The HAS notes the importance of control measures as complementary protective measures of maternal vaccination and passive immunisation of infants with monoclonal antibodies against RSV.

The HAS stresses the importance of setting up enhanced pharmacovigilance (post-approval safety studies) in particular with a view to documenting the potential risk of premature births.

This opinion may be reviewed with regard to the complete findings of ongoing trials, future trials, pharmacovigilance data and real-life data from other countries.