Respiratory syncytial virus vaccine development is making great strides

Respiratory syncytial virus vaccine development is making great strides

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In this pre-winter period, everyone has heard of respiratory infections and, in particular, infant bronchiolitis and its main culprit, the respiratory syncytial virus (RSV). This virus, which circulates actively from autumn to spring, infects 90% of children during the first two years of their life. In some cases, the consequences can be serious: the infection generally begins with rhinitis, which can progress to bronchiolitis and sometimes to pneumonia with respiratory distress. Hospitalization is then necessary. But RSV does not spare adults, especially over 60, for whom the infection can have the same consequences as the flu.

For years, research has been carried out to develop a vaccine, but the company has encountered several difficulties (1). They are due, among other things, to the fact that there are two types of RSV (A and B), that the surface protein F which carries the main antigens can be in several conformations, and that infection facilitation phenomena can be triggered by certain vaccine formulations. In the 1960s, two deaths occurred in previously uninfected children vaccinated with a formalin-inactivated vaccine who subsequently presented with severe RSV infection. A difficulty is also due to the fact that it is necessary to protect newborns and very young children, while their immune system is still immature. Several approaches are therefore used today, based on different platforms: whole virus, subunits, adjuvants to guide the immune response, vectorized vaccines, and now messenger RNA. The formulas are adapted according to the populations to be protected: young children, the elderly, pregnant women (the aim then being to protect the unborn child by transferring antibodies).

More than thirty candidate vaccines against RSV are thus in development, and 9 have reached phase III of their clinical trials. The most advanced are undoubtedly those of GSK (a vaccine intended for elderly adults, consisting of a recombinant viral protein F and the “in-house” adjuvant AS01E, whose EMA has agreed to examine the application for AMM) and Pfizer (an equally proteinaceous, bivalent vaccine, administered during pregnancy, which is very effective in protecting newborns during the first months of life) (2).

Using RNA technology, Moderna is developing a multivalent vaccine against SARS-CoV-2, influenza viruses and RSV; trials are in progress.

Advances in knowledge of immunity and the use of adjuvants to guide the vaccine response give hope in the near future for the development of effective vaccines in very young children (3).

In November 2022, the product developed by Sanofi and AstraZeneca (Beyfortus® or nirsevimab) received marketing authorization from the European Commission (4). It is not strictly speaking a vaccine, but a long-lived antibody, capable of protecting, in a single administration, newborns and infants during a whole first season of exposure to RSV. . Nirsevimab thus differs from palivizumab (Synagis®), another active antibody authorized since 1999, but which must be administered every month by intramuscular injection during the period of circulation of the virus.

References

  1. A. Killikelly, M. Tunis et al. Overview of the respiratory syncytial virus vaccine candidate pipeline in Canada.
  2. Press release. Pfizer Announces Positive Top-Line Data of Phase 3 Global Maternal Immunization Trial for its Bivalent Respiratory Syncytial Virus (RSV) Vaccine Candidate.
  3. SD van Haren, GK Pedersen et al. CAF08 adjuvant enables single dose protection against respiratory syncytial virus infection in murine newborns.
  4. Sanofi Pasteur press release. Press release: The European Commission grants the world’s first authorization for Beyfortus® (nirsevimab) for the prevention of RSV infections in infants.

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