Pediatric Infection and Vaccine

The Korean Society of Pediatric Infectious Diseases (대한소아감염학회)
권호 표지
DOI QR코드

DOI QR Code

Recent Advances in the Prevention of RSV in Neonates and Young Infants

  • Ki Wook Yun (Department of Pediatrics, Seoul National University College of Medicine)
  • Received : 2022.09.28
  • Accepted : 2023.06.11
  • Published : 2023.07.03
Download PDF
⟨ Previous Next ⟩

Abstract

Respiratory syncytial virus (RSV) is a pathogen with a high burden of disease and social cost among infants worldwide, but the development of a vaccine has been delayed. The recent understanding of the pathogenesis of RSV, progress in reverse genetics, and successful implementation of other maternal immunizations have prompted the recent rapid development of monoclonal antibodies (mAbs) and vaccines for RSV prevention. Phase 3 clinical trials for two next-generation mAbs (nirsevimab and clesrovimab) and two maternal RSV pre-F vaccines are currently underway or have been recently completed. Soon, we might be able to protect young infants through long-acting mAbs and/or maternal immunization. Additionally, the development of live-attenuated vaccine candidates that are capable of avoiding enhanced RSV disease is ongoing. We need to gain familiarity with these newly developed strategies and collect epidemiological data on domestic RSV to adequately prepare for a new era of RSV prevention.

Respiratory syncytial virus (RSV)는 전 세계적으로 영유아에게 질병 부담과 사회적 비용이 매우 높은 병원체이지만 그 백신 개발은 상당히 지연되고 있다. 현재로선 단기-지속형 단클론항체인 palivizumab이 유일한 예방법이다. 그러나 최근 RSV 감염의 병태생리학에 대한 이해, 유전학의 발전, 모체 예방접종의 성공적인 시행 등으로 RSV 예방을 위한 단일클론 항체 및 백신의 개발이 급속히 추진되고 있다. 현재 2개의 장기-지속형 단클론항체 제제(nirsevimab 및 clesrovimab)와 2개의 모체 RSV pre-F 백신이 임상 3상 시험을 진행 중이거나 막 완료하였으며, 지금까지의 결과는 효과와 안전성 측면에서 매우 긍정적이다. 가까운 장래에 장기-지속형 단클론항체와 모체 예방접종을 통해 고위험군은 물론이고 기저질환이 없는 신생아 및 영유아들을 RSV로부터 효과적으로 보호할 수 있을 것으로 기대한다. RSV 예방의 새로운 시대에 빠르고 적절히 대비하기 위해서는 이러한 새로운 전략들에 익숙해지고 국내 RSV에 대한 역학 자료들을 계속 수집해 나갈 필요가 있다.

Keywords

References

  1. Shi T, McAllister DA, O'Brien KL, Simoes EA, Madhi SA, Gessner BD, et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet 2017;390:946-58. https://doi.org/10.1016/S0140-6736(17)30938-8
  2. Mejias A, Rodriguez-Fernandez R, Oliva S, Peeples ME, Ramilo O. The journey to a respiratory syncytial virus vaccine. Ann Allergy Asthma Immunol 2020;125:36-46. https://doi.org/10.1016/j.anai.2020.03.017
  3. Magro M, Mas V, Chappell K, Vazquez M, Cano O, Luque D, et al. Neutralizing antibodies against the preactive form of respiratory syncytial virus fusion protein offer unique possibilities for clinical intervention. Proc Natl Acad Sci U S A 2012;109:3089-94. https://doi.org/10.1073/pnas.1115941109
  4. Flynn JA, Durr E, Swoyer R, Cejas PJ, Horton MS, Galli JD, et al. Stability characterization of a vaccine antigen based on the respiratory syncytial virus fusion glycoprotein. PLoS One 2016;11:e0164789.
  5. PATH. RSV vaccine and mAb snapshot [Internet]. Addis Ababa: PATH; 2023 [cited 2022 May 4]. Available from: https://www.path.org/resources/rsv-vaccine-and-mab-snapshot/.
  6. Simoes EA. The burden of respiratory syncytial virus lower respiratory tract disease in infants in the United States: a synthesis. J Infect Dis 2022;226 Suppl 2:S143-7. https://doi.org/10.1093/infdis/jiac211
  7. Thomas E, Mattila JM, Lehtinen P, Vuorinen T, Waris M, Heikkinen T. Burden of respiratory syncytial virus infection during the first year of life. J Infect Dis 2021;223:811-7. https://doi.org/10.1093/infdis/jiaa754
  8. Kang JM, Lee J, Kim YK, Cho HK, Park SE, Kim KH, et al. Pediatric intensive care unit admission due to respiratory syncytial virus: Retrospective multicenter study. Pediatr Int 2019;61:688-96. https://doi.org/10.1111/ped.13893
  9. Yun KW, Choi EH, Lee HJ. Molecular epidemiology of respiratory syncytial virus for 28 consecutive seasons (1990-2018) and genetic variability of the duplication region in the G gene of genotypes ON1 and BA in South Korea. Arch Virol 2020;165:1069-77. https://doi.org/10.1007/s00705-020-04580-z
  10. Kim YK, Song SH, Ahn B, Lee JK, Choi JH, Choi SH, et al. Shift in clinical epidemiology of human parainfluenza virus type 3 and respiratory syncytial virus B infections in Korean children before and during the COVID-19 pandemic: a multicenter retrospective study. J Korean Med Sci 2022;37:e215.
  11. The IMpact-RSV Study Group. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics 1998;102:531-7. https://doi.org/10.1542/peds.102.3.531
  12. Feltes TF, Cabalka AK, Meissner HC, Piazza FM, Carlin DA, Top FH Jr, et al. Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease. J Pediatr 2003;143:532-40. https://doi.org/10.1067/S0022-3476(03)00454-2
  13. Lee JH, Kim CS, Chang YS, Choi JH; Committee on Data Collection and Statistical Analysis of the Korean Society of Neonatology. Respiratory syncytial virus related readmission in preterm infants less than 34 weeks' gestation following discharge from a neonatal intensive care unit in Korea. J Korean Med Sci 2015;30 Suppl 1:S104-10. https://doi.org/10.3346/jkms.2015.30.S1.S104
  14. Andabaka T, Nickerson JW, Rojas-Reyes MX, Rueda JD, Bacic Vrca V, Barsic B. Monoclonal antibody for reducing the risk of respiratory syncytial virus infection in children. Cochrane Database Syst Rev 2013:CD006602.
  15. Paes BA, Saleem M, Li A, Lanctot KL, Mitchell I; CARESS Investigators. Caress investigators. Respiratory syncytial virus prophylaxis in immunocompromised children: outcomes from the Canadian RSV evaluation study of palivizumab registry over twelve seasons (2005-2017). Pediatr Infect Dis J 2020;39:539-45. https://doi.org/10.1097/INF.0000000000002665
  16. Wang DY, Saleem M, Paes BA, Mitchell I, Li A, Lanctot KL, et al. Respiratory syncytial virus prophylaxis in neurologic and muscular disorders in the Canadian respiratory syncytial virus evaluation study of palivizumab. Pediatr Infect Dis J 2019;38:775-80. https://doi.org/10.1097/INF.0000000000002297
  17. Kim SY, Lee KE, Kang SY, Choi EH, Lee HJ. Evaluation of timeliness of palivizumab immunoprophylaxis based on the epidemic period of respiratory syncytial virus: 22 year experience in a single center. Pediatr Infect Vaccine 2015;22:172-7. https://doi.org/10.14776/piv.2015.22.3.172
  18. Zhu Q, McLellan JS, Kallewaard NL, Ulbrandt ND, Palaszynski S, Zhang J, et al. A highly potent extended half-life antibody as a potential RSV vaccine surrogate for all infants. Sci Transl Med 2017;9:eaaj1928.
  19. Griffin MP, Yuan Y, Takas T, Domachowske JB, Madhi SA, Manzoni P, et al. Single-dose nirsevimab for prevention of RSV in preterm infants. N Engl J Med 2020;383:415-25. https://doi.org/10.1056/NEJMoa1913556
  20. Hammitt LL, Dagan R, Yuan Y, Baca Cots M, Bosheva M, Madhi SA, et al. Nirsevimab for prevention of RSV in healthy late-preterm and term infants. N Engl J Med 2022;386:837-46. https://doi.org/10.1056/NEJMoa2110275
  21. Domachowske J, Madhi SA, Simoes EA, Atanasova V, Cabanas F, Furuno K, et al. Safety of nirsevimab for RSV in infants with heart or lung disease or prematurity. N Engl J Med 2022;386:892-4. https://doi.org/10.1056/NEJMc2112186
  22. Tang A, Chen Z, Cox KS, Su HP, Callahan C, Fridman A, et al. A potent broadly neutralizing human RSV antibody targets conserved site IV of the fusion glycoprotein. Nat Commun 2019;10:4153.
  23. Simoes EA, Forleo-Neto E, Geba GP, Kamal M, Yang F, Cicirello H, et al. Suptavumab for the prevention of medically attended respiratory syncytial virus infection in preterm infants. Clin Infect Dis 2021;73:e4400-8. https://doi.org/10.1093/cid/ciaa951
  24. Langedijk AC, Harding ER, Konya B, Vrancken B, Lebbink RJ, Evers A, et al. A systematic review on global RSV genetic data: Identification of knowledge gaps. Rev Med Virol 2022;32:e2284.
  25. Zhu Q, Lu B, McTamney P, Palaszynski S, Diallo S, Ren K, et al. Prevalence and significance of substitutions in the fusion protein of respiratory syncytial virus resulting in neutralization escape from antibody MEDI8897. J Infect Dis 2018;218:572-80. https://doi.org/10.1093/infdis/jiy189
  26. Oliveira DB, Iwane MK, Prill MM, Weinberg GA, Williams JV, Griffin MR, et al. Molecular characterization of respiratory syncytial viruses infecting children reported to have received palivizumab immunoprophylaxis. J Clin Virol 2015;65:26-31. https://doi.org/10.1016/j.jcv.2015.01.016
  27. Choi SH, Park KS, Kim YJ. Analysis of respiratory syncytial virus fusion protein from clinical isolates of Korean children in palivizumab era, 2009-2015. J Infect Chemother 2019;25:514-9. https://doi.org/10.1016/j.jiac.2019.02.013
  28. Kim HW, Canchola JG, Brandt CD, Pyles G, Chanock RM, Jensen K, et al. Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. Am J Epidemiol 1969;89:422-34. https://doi.org/10.1093/oxfordjournals.aje.a120955
  29. Kapikian AZ, Mitchell RH, Chanock RM, Shvedoff RA, Stewart CE. An epidemiologic study of altered clinical reactivity to respiratory syncytial (RS) virus infection in children previously vaccinated with an inactivated RS virus vaccine. Am J Epidemiol 1969;89:405-21. https://doi.org/10.1093/oxfordjournals.aje.a120954
  30. Albrecht M, Arck PC. Vertically transferred immunity in neonates: mothers, mechanisms and mediators. Front Immunol 2020;11:555.
  31. Buchwald AG, Graham BS, Traore A, Haidara FC, Chen M, Morabito K, et al. Respiratory syncytial virus (RSV) neutralizing antibodies at birth predict protection from RSV illness in infants in the first 3 months of life. Clin Infect Dis 2021;73:e4421-7. https://doi.org/10.1093/cid/ciaa648
  32. Roca A, Abacassamo F, Loscertales MP, Quinto L, Gomez-Olive X, Fenwick F, et al. Prevalence of respiratory syncytial virus IgG antibodies in infants living in a rural area of Mozambique. J Med Virol 2002;67:616-23. https://doi.org/10.1002/jmv.10148
  33. Munoz FM, Piedra PA, Glezen WP. Safety and immunogenicity of respiratory syncytial virus purified fusion protein-2 vaccine in pregnant women. Vaccine 2003;21:3465-7. https://doi.org/10.1016/S0264-410X(03)00352-9
  34. Koivisto K, Nieminen T, Mejias A, Capella Gonzalez C, Ye F, Mertz S, et al. Respiratory Syncytial Virus (RSV)-specific antibodies in pregnant women and subsequent risk of RSV hospitalization in young infants. J Infect Dis 2022;225:1189-96. https://doi.org/10.1093/infdis/jiab315
  35. Glenn GM, Fries LF, Thomas DN, Smith G, Kpamegan E, Lu H, et al. A randomized, blinded, controlled, dose-ranging study of a respiratory syncytial virus recombinant fusion (F) nanoparticle vaccine in healthy women of childbearing age. J Infect Dis 2016;213:411-22. https://doi.org/10.1093/infdis/jiv406
  36. Munoz FM, Swamy GK, Hickman SP, Agrawal S, Piedra PA, Glenn GM, et al. Safety and immunogenicity of a respiratory syncytial virus fusion (F) protein nanoparticle vaccine in healthy third-trimester pregnant women and their infants. J Infect Dis 2019;220:1802-15. https://doi.org/10.1093/infdis/jiz390
  37. Madhi SA, Polack FP, Piedra PA, Munoz FM, Trenholme AA, Simoes EA, et al. Respiratory syncytial virus vaccination during pregnancy and effects in infants. N Engl J Med 2020;383:426-39. https://doi.org/10.1056/NEJMoa1908380
  38. Beran J, Lickliter JD, Schwarz TF, Johnson C, Chu L, Domachowske JB, et al. Safety and immunogenicity of 3 formulations of an investigational respiratory syncytial virus vaccine in nonpregnant women: results from 2 phase 2 trials. J Infect Dis 2018;217:1616-25. https://doi.org/10.1093/infdis/jiy065
  39. Schwarz TF, McPhee RA, Launay O, Leroux-Roels G, Talli J, Picciolato M, et al. Immunogenicity and safety of 3 formulations of a respiratory syncytial virus candidate vaccine in nonpregnant women: a phase 2, randomized trial. J Infect Dis 2019;220:1816-25. https://doi.org/10.1093/infdis/jiz395
  40. Walsh EE, Falsey AR, Scott DA, Gurtman A, Zareba AM, Jansen KU, et al. A randomized phase 1/2 study of a respiratory syncytial virus prefusion F vaccine. J Infect Dis 2022;225:1357-66. https://doi.org/10.1093/infdis/jiab612
  41. Simoes EA, Center KJ, Tita AT, Swanson KA, Radley D, Houghton J, et al. Prefusion F protein-based respiratory syncytial virus immunization in pregnancy. N Engl J Med 2022;386:1615-26. https://doi.org/10.1056/NEJMoa2106062
  42. Wright PF, Karron RA, Belshe RB, Shi JR, Randolph VB, Collins PL, et al. The absence of enhanced disease with wild type respiratory syncytial virus infection occurring after receipt of live, attenuated, respiratory syncytial virus vaccines. Vaccine 2007;25:7372-8. https://doi.org/10.1016/j.vaccine.2007.08.014
  43. Buchholz UJ, Cunningham CK, Muresan P, Gnanashanmugam D, Sato P, Siberry GK, et al. Live respiratory syncytial virus (RSV) vaccine candidate containing stabilized temperature-sensitivity mutations is highly attenuated in RSV-seronegative infants and children. J Infect Dis 2018;217:1338-46. https://doi.org/10.1093/infdis/jiy066
  44. McFarland EJ, Karron RA, Muresan P, Cunningham CK, Valentine ME, Perlowski C, et al. Live-attenuated respiratory syncytial virus vaccine candidate with deletion of RNA synthesis regulatory protein M2-2 is highly immunogenic in children. J Infect Dis 2018;217:1347-55. https://doi.org/10.1093/infdis/jiy040
  45. McFarland EJ, Karron RA, Muresan P, Cunningham CK, Libous J, Perlowski C, et al. Live respiratory syncytial virus attenuated by M2-2 deletion and stabilized temperature sensitivity mutation 1030s is a promising vaccine candidate in children. J Infect Dis 2020;221:534-43. https://doi.org/10.1093/infdis/jiz603
  46. Williams K, Bastian AR, Feldman RA, Omoruyi E, de Paepe E, Hendriks J, et al. Phase 1 safety and immunogenicity study of a respiratory syncytial virus vaccine with an adenovirus 26 vector encoding prefusion F (Ad26.RSV.preF) in adults aged ≥60 years. J Infect Dis 2020;222:979-88. https://doi.org/10.1093/infdis/jiaa193
  47. Sadoff J, De Paepe E, DeVincenzo J, Gymnopoulou E, Menten J, Murray B, et al. Prevention of respiratory syncytial virus infection in healthy adults by a single immunization of Ad26.RSV.preF in a human challenge study. J Infect Dis 2022;226:396-406. https://doi.org/10.1093/infdis/jiab003
  48. Aliprantis AO, Shaw CA, Griffin P, Farinola N, Railkar RA, Cao X, et al. A phase 1, randomized, placebo-controlled study to evaluate the safety and immunogenicity of an mRNA-based RSV prefusion F protein vaccine in healthy younger and older adults. Hum Vaccin Immunother 2021;17:1248-61. https://doi.org/10.1080/21645515.2020.1829899