Development of vaccines against respiratory virus…

In this period before winter, everyone has heard about respiratory infections and especially about 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 lives. 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. Then hospitalization is necessary. But RSV does not spare adults, especially those over 60, for whom the infection can have the same consequences as the flu.

Research has been going on for years to develop a vaccine, but the company has run into some 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 major antigens can be in several conformations, and that the facilitation of infection phenomena can be caused by several 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. Therefore, several approaches are used today, based on different platforms: whole virus, subunits, adjuvants to direct the immune response, vectorized vaccines and now messenger RNA. The formulas are tailored according to the populations to be protected: young children, the elderly, pregnant women (the goal then is to protect the unborn child by transferring antibodies).

Thus, more than thirty candidate vaccines against RSV are in development, and 9 have reached phase III of their clinical trials. The most advanced are undoubtedly those of GSK (a vaccine intended for older 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 protein. , 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 ongoing.

Advances in the knowledge of immunity and the use of adjuvants to guide the vaccine response provide 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 a vaccine, but a long-lived antibody capable of protecting, with a single administration, newborns and infants throughout the first season of exposure to RSV. Thus, Nirsevimab differs from palivizumab (Synagis®), another active antibody authorized since 1999, but which must be administered monthly by intramuscular injection during the period of virus circulation.

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 global maternal immunization phase 3 data for its bivalent respiratory syncytial virus (RSV) vaccine candidate.
  3. SD van Haren, GK Pedersen etc. CAF08 adjuvant provides single-dose protection against respiratory syncytial virus infection in neonatal mice.
  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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