Respiratory syncytial virus vaccine

A respiratory syncytial virus vaccine (RSV vaccine) is a vaccine which prevents infection by respiratory syncytial virus. As of 2021, no licensed vaccine against RSV exists.

Attempts to develop an RSV vaccine began in the 1960s with an unsuccessful inactivated vaccine developed by exposing the RSV virus to formalin (formalin-inactivated RSV (FI-RSV)).[1] Unfortunately, this vaccine induced a phenomenon that came to be known as vaccine-associated enhanced respiratory disease (VAERD), in which children who had not previously been exposed to RSV and were subsequently vaccinated would develop a severe form of RSV disease if exposed to the virus itself, including fever, wheezing, and bronchopneumonia.[1] Some eighty percent of such children (vs. 5% of virus-exposed controls) were hospitalized, and two children died of lethal lung inflammatory response during the first natural RSV infection after vaccination of RSV-naive infants.[1] This disaster hindered vaccine development for many years to come.[1]

A 1998 paper reported that research toward developing a vaccine had advanced greatly over the previous 10 years.[2] The desired vaccine would prevent lower respiratory infection from RSV in at-risk populations and if possible be useful in other populations with less risk.[2] Twenty years later, a 2019 paper similarly claimed that research toward developing a vaccine had advanced greatly over the prior 10 years.[3] The same study predicted that a vaccine would be available within 10 years.[3]

The current types of vaccines which are in research are particle-based vaccines, attenuated vaccines, mRNA vaccines, protein subunit vaccines, or vector-based vaccines.[4][5]

A vaccine called GSK3888550A and developed by GlaxoSmithKline (GSK) entered phase 3 clinical trials in November 2020.[6] Barney S. Graham and Peter Kwong of the National Institute of Allergy and Infectious Diseases' Vaccine Research Center, along with Jason McLellan, a former postdoctoral researcher at VRC and a professor at The University of Texas at Austin, spearheaded its development.[7] The vaccine's antigen, a stabilized version of the RSV F protein, was developed using structure-based vaccine design.[8][9] In August 2021, Moderna received US FDA fast track designation for their Respiratory Syncytial Virus Vaccine.[10]

As of October 10, 2022, at least four companies are testing candidate RSV vaccines based on stabilized prefusion F proteins in older adults in Phase 3 trials: GSK_plc, Pfizer, Johnson & Johnson, and Moderna.[11][12]

References

  1. Acosta PL, Caballero MT, Polack FP (December 16, 2015). "Brief History and Characterization of Enhanced Respiratory Syncytial Virus Disease". Clin Vaccine Immunol. 23 (3): 189–195. doi:10.1128/CVI.00609-15. PMC 4783420. PMID 26677198.
  2. Dudas, RA; Karron, RA (July 1998). "Respiratory syncytial virus vaccines". Clinical Microbiology Reviews. 11 (3): 430–439. doi:10.1128/CMR.11.3.430. PMC 88889. PMID 9665976.
  3. Mejias, Asuncion; Rodriguez-Fernandez, Rosa; Peeples, Mark E.; Ramilo, Octavio (October 2019). "Respiratory Syncytial Virus Vaccines". The Pediatric Infectious Disease Journal. 38 (10): e266–e269. doi:10.1097/INF.0000000000002404. PMC 8404780. PMID 31335571.
  4. Mazur, Natalie I; Higgins, Deborah; Nunes, Marta C; Melero, José A; Langedijk, Annefleur C; Horsley, Nicole; et al. (October 2018). "The respiratory syncytial virus vaccine landscape: lessons from the graveyard and promising candidates" (PDF). The Lancet Infectious Diseases. 18 (10): e295–e311. doi:10.1016/S1473-3099(18)30292-5. PMID 29914800. S2CID 49300571.
  5. Powell, Kendall (2021-12-10). "The race to make vaccines for a dangerous respiratory virus". Nature. 600 (7889): 379–380. Bibcode:2021Natur.600..379P. doi:10.1038/d41586-021-03704-y. PMID 34893769. S2CID 245021172.
  6. "Hoping for an endgame, GSK kick-starts phase 3 RSV vaccine trial in pregnant women". Fierce Biotech. 24 Nov 2020. Retrieved 3 June 2021.
  7. McLellan JS, Graham BS, Kwong PD, et al. (November 1, 2013). "Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory Syncytial Virus". Science. 342 (6158): 592–598. Bibcode:2013Sci...342..592M. doi:10.1126/science.1243283. PMC 4461862. PMID 24179220.
  8. Cohen, Jon (November 1, 2013). "Structural Biology Triumph Offers Hope Against a Childhood Killer". Science. 342 (6158): 546–547. Bibcode:2013Sci...342Q.546C. doi:10.1126/science.342.6158.546-a. PMID 24179197.
  9. Crank MC, McLellan JS, Ledgerwood JE, Graham BS, the VRC 317 Study Team, et al. (August 2, 2019). "A proof of concept for structure-based vaccine design targeting RSV in humans". Science. 365 (6452): 505–509. Bibcode:2019Sci...365..505C. doi:10.1126/science.aav9033. PMID 31371616.
  10. "Moderna Receives FDA Fast Track Designation for Respiratory Syncytial Virus (RSV) Vaccine (mRNA-1345)" (Press release). Business Wire. August 3, 2021.
  11. "For decades, fear and failure in the hunt for an RSV vaccine. Now, success". Washington Post. 10 Oct 2022. Retrieved 11 Oct 2022.
  12. "This UT Scientist Helped Spare Millions From COVID-19. Now He's Unmasking Other Killer Viruses". Texas Monthly. 10 Oct 2022. Retrieved 13 Oct 2022.
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