The Journey to an RSV Vaccine

Objective: The high burden associated with respiratory syncytial virus (RSV), has made the development of RSV vaccine(s) a global health high priority. This review summarizes the ourney to an RSV vaccine, the different strategies and challenges associated with the development of preventive strategies for RSV, and the diverse products that are undergoing clinical testing. Data sources: Studies on RSV biology, immunology, epidemiology and monoclonal antibodies and vaccines were searched using MEDLINE. We also searched https://path.org and ClinicalTrials.gov for updated information regarding the status of RSV vaccines and monoclonal antibodies undergoing clinical trials. Study selections: We selected relevant studies conducted in infants and young children, pregnant women and the elderly for the prevention of RSV infection. Results: Identification of a safe and immunogenic vaccine has been an important but elusive initiative for over 60 years for different reasons including the legacy of formalininactivated vaccine, our limited understanding of the immune response to RSV and how it relates to clinical disease severity or the need for different endpoints according to the different vaccine platforms. Nevertheless, there are currently 39 vaccines and monoclonal antibodies under development and 19 undergoing clinical trials. in our knowledge of molecular and and there promising and undergoing clinical that hope to offer populations

[1]  P. Zachariah,et al.  Epidemiology, clinical features, and resource utilization associated with respiratory syncytial virus in the community and hospital , 2020, Influenza and other respiratory viruses.

[2]  F. Polack,et al.  Respiratory Failure and Death in Vulnerable Premature Children With Lower Respiratory Tract Illness , 2020, The Journal of infectious diseases.

[3]  O. Ramilo,et al.  Risk of childhood wheeze and asthma after respiratory syncytial virus infection in full‐term infants , 2020, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[4]  C. Reed,et al.  Estimated Burden of Community-Onset Respiratory Syncytial Virus–Associated Hospitalizations Among Children Aged <2 Years in the United States, 2014–15 , 2019, Journal of the Pediatric Infectious Diseases Society.

[5]  G. Gray,et al.  A Mini-Review of Adverse Lung Transplant Outcomes Associated With Respiratory Viruses , 2019, Front. Immunol..

[6]  R. Karron,et al.  Live respiratory syncytial virus attenuated by M2-2 deletion and stabilized temperature sensitivity mutation 1030s is a promising vaccine candidate in children. , 2019, The Journal of infectious diseases.

[7]  M. Meltzer,et al.  Estimating the impact of multiple immunization products on medically-attended respiratory syncytial virus (RSV) infections in infants , 2019, Vaccine.

[8]  R. Karron,et al.  Safety and Immunogenicity of the Respiratory Syncytial Virus Vaccine RSV/ΔNS2/Δ1313/I1314L in RSV-Seronegative Children , 2019, The Journal of infectious diseases.

[9]  O. Ramilo,et al.  Respiratory Syncytial Virus Vaccines: Are We Making Progress? , 2019, The Pediatric infectious disease journal.

[10]  E. Simões,et al.  901. MEDI8897 Prevents Serious RSV Disease in Healthy Preterm Infants , 2019, Open Forum Infectious Diseases.

[11]  H. Su,et al.  A potent broadly neutralizing human RSV antibody targets conserved site IV of the fusion glycoprotein , 2019, Nature Communications.

[12]  B. Graham.  Immunological goals for respiratory syncytial virus vaccine development. , 2019, Current opinion in immunology.

[13]  A. Curns,et al.  Respiratory Syncytial Virus-Associated Outpatient Visits Among Children Younger Than 24 Months. , 2019, Journal of the Pediatric Infectious Diseases Society.

[14]  O. Ramilo,et al.  Recent Trends in RSV Immunoprophylaxis: Clinical Implications for the Infant , 2019, American Journal of Perinatology.

[15]  P. Piedra,et al.  Clinical characteristics and outcomes of respiratory syncytial virus infection in pregnant women , 2019, Vaccine.

[16]  R. Mikolajczyk,et al.  Global Disease Burden Estimates of Respiratory Syncytial Virus-Associated Acute Respiratory Infection in Older Adults in 2015: A Systematic Review and Meta-Analysis. , 2019, The Journal of infectious diseases.

[17]  O. Ramilo,et al.  Viral Load Dynamics and Clinical Disease Severity in Infants With Respiratory Syncytial Virus Infection , 2018, The Journal of infectious diseases.

[18]  O. Ramilo,et al.  The respiratory syncytial virus vaccine landscape: lessons from the graveyard and promising candidates. , 2018, The Lancet. Infectious diseases.

[19]  P. Piedra,et al.  A Cross-sectional Surveillance Study of the Frequency and Etiology of Acute Respiratory Illness Among Pregnant Women , 2018, The Journal of infectious diseases.

[20]  P. Cane,et al.  Continuous Invasion by Respiratory Viruses Observed in Rural Households During a Respiratory Syncytial Virus Seasonal Outbreak in Coastal Kenya , 2018, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[21]  A. Sivasubramanian,et al.  Infants Infected with Respiratory Syncytial Virus Generate Potent Neutralizing Antibodies that Lack Somatic Hypermutation , 2018, Immunity.

[22]  M. P. Griffin,et al.  Safety, Tolerability and Pharmacokinetics of MEDI8897, an Extended Half-life Single-dose Respiratory Syncytial Virus Prefusion F-targeting Monoclonal Antibody Administered as a Single Dose to Healthy Preterm Infants , 2018, The Pediatric infectious disease journal.

[23]  Stephanie A. Jones,et al.  Burden of Respiratory Syncytial Virus Infection in South African Human Immunodeficiency Virus (HIV)-Infected and HIV-Uninfected Pregnant and Postpartum Women: A Longitudinal Cohort Study , 2017, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[24]  Sara M. Johnson,et al.  Prefusion F, Postfusion F, G Antibodies, and Disease Severity in Infants and Young Children With Acute Respiratory Syncytial Virus Infection , 2017, The Journal of infectious diseases.

[25]  C. Byington,et al.  Identifying Gaps in Respiratory Syncytial Virus Disease Epidemiology in the United States Prior to the Introduction of Vaccines. , 2017, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[26]  M. Lucero,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 , 2017, The Lancet.

[27]  M. P. Griffin,et al.  Passive and active immunization against respiratory syncytial virus for the young and old , 2017, Expert review of vaccines.

[28]  N. Patel,et al.  A highly potent extended half-life antibody as a potential RSV vaccine surrogate for all infants , 2017, Science Translational Medicine.

[29]  B. Graham.  Vaccine development for respiratory syncytial virus. , 2017, Current opinion in virology.

[30]  C. López,et al.  The innate immune response to RSV: Advances in our understanding of critical viral and host factors. , 2017, Vaccine.

[31]  M. Kanekiyo,et al.  Pre-fusion F is absent on the surface of formalin-inactivated respiratory syncytial virus , 2016, Scientific Reports.

[32]  J. Katz,et al.  Clinical Presentation and Birth Outcomes Associated with Respiratory Syncytial Virus Infection in Pregnancy , 2016, PloS one.

[33]  P. Nymadawa,et al.  Burden of Influenza and Respiratory Syncytial Virus Infection in Pregnant Women and Infants Under 6 Months in Mongolia: A Prospective Cohort Study , 2016, PloS one.

[34]  Sara M. Johnson,et al.  Respiratory Syncytial Virus Uses CX3CR1 as a Receptor on Primary Human Airway Epithelial Cultures , 2015, PLoS pathogens.

[35]  R. Karron,et al.  A gene deletion that up-regulates viral gene expression yields an attenuated RSV vaccine with improved antibody responses in children , 2015, Science Translational Medicine.

[36]  C. Byington,et al.  Respiratory Syncytial Virus–Associated Mortality in Hospitalized Infants and Young Children , 2015, Pediatrics.

[37]  T. Mazzulli,et al.  Respiratory syncytial virus infection-associated hospitalization in adults: a retrospective cohort study , 2014, BMC Infectious Diseases.

[38]  Eneida A. Mendonça,et al.  Clinical Practice Guideline: The Diagnosis, Management, and Prevention of Bronchiolitis , 2014, Pediatrics.

[39]  P. Ljungman.  Respiratory syncytial virus in hematopoietic cell transplant recipients: factors determining progression to lower respiratory tract disease. , 2014, The Journal of infectious diseases.

[40]  S. Niewiesk,et al.  Synergistic induction of interferon α through TLR-3 and TLR-9 agonists stimulates immune responses against measles virus in neonatal cotton rats. , 2014, Vaccine.

[41]  J. Banchereau,et al.  Whole Blood Gene Expression Profiles to Assess Pathogenesis and Disease Severity in Infants with Respiratory Syncytial Virus Infection , 2013, PLoS medicine.

[42]  Bernhard Resch,et al.  Burden of respiratory syncytial virus infection in young children. , 2012, World journal of clinical pediatrics.

[43]  P. Kwong,et al.  Structure of Respiratory Syncytial Virus Fusion Glycoprotein in the Postfusion Conformation Reveals Preservation of Neutralizing Epitopes , 2011, Journal of Virology.

[44]  Rafia Bhore,et al.  Risk Factors in Children Hospitalized With RSV Bronchiolitis Versus Non–RSV Bronchiolitis , 2010, Pediatrics.

[45]  J. Oxford,et al.  Viral load drives disease in humans experimentally infected with respiratory syncytial virus. , 2010, American journal of respiratory and critical care medicine.

[46]  J. Rossen,et al.  Disease severity and viral load are correlated in infants with primary respiratory syncytial virus infection in the community† , 2010, Journal of medical virology.

[47]  S. Madhi,et al.  Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis , 2010, The Lancet.

[48]  A. Wald,et al.  Respiratory Virus Pneumonia after Hematopoietic Cell Transplantation (HCT): Associations between Viral Load in Bronchoalveolar Lavage Samples, Viral RNA Detection in Serum Samples, and Clinical Outcomes of HCT , 2010, The Journal of infectious diseases.

[49]  L. Avendaño,et al.  Impaired Immune Response in Severe Human Lower Tract Respiratory Infection by Respiratory Syncytial Virus , 2009, The Pediatric infectious disease journal.

[50]  C. Macias,et al.  Immunopathogenesis of respiratory syncytial virus bronchiolitis. , 2007, The Journal of infectious diseases.

[51]  M. O’Shea,et al.  Symptomatic respiratory syncytial virus infection in previously healthy young adults living in a crowded military environment. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[52]  E. Walsh,et al.  Respiratory syncytial virus infection in elderly and high-risk adults. , 2005, The New England journal of medicine.

[53]  T. Out,et al.  Human CD8(+) T cell responses against five newly identified respiratory syncytial virus-derived epitopes. , 2004, The Journal of general virology.

[54]  E. Walsh,et al.  Humoral and mucosal immunity in protection from natural respiratory syncytial virus infection in adults. , 2004, The Journal of infectious diseases.

[55]  S. J. Hoffman,et al.  A Role for Immune Complexes in Enhanced Respiratory Syncytial Virus Disease , 2002, The Journal of experimental medicine.

[56]  P. Collins,et al.  Respiratory Syncytial Virus Infection of Human Airway Epithelial Cells Is Polarized, Specific to Ciliated Cells, and without Obvious Cytopathology , 2002, Journal of Virology.

[57]  H. Tsutsumi.  [Humanized respiratory syncytial virus monoclonal antibody]. , 2002, Nihon rinsho. Japanese journal of clinical medicine.

[58]  C. Hall,et al.  Respiratory syncytial virus infections in previously healthy working adults. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[59]  L. Anderson,et al.  CX3C chemokine mimicry by respiratory syncytial virus G glycoprotein , 2001, Nature Immunology.

[60]  P. Collins,et al.  Iduronic acid-containing glycosaminoglycans on target cells are required for efficient respiratory syncytial virus infection. , 2000, Virology.

[61]  R. Holman,et al.  Bronchiolitis-associated hospitalizations among US children, 1980-1996. , 1999, JAMA.

[62]  D. Sherrill,et al.  Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years , 1999, The Lancet.

[63]  O. Ramilo,et al.  Elevated cytokine concentrations in the nasopharyngeal and tracheal secretions of children with respiratory syncytial virus disease. , 1999, The Pediatric infectious disease journal.

[64]  D. Pfarr,et al.  Development of a humanized monoclonal antibody (MEDI-493) with potent in vitro and in vivo activity against respiratory syncytial virus. , 1997, The Journal of infectious diseases.

[65]  V. Hammersley,et al.  Acute viral infections of upper respiratory tract in elderly people living in the community: comparative, prospective, population based study of disease burden , 1997, BMJ.

[66]  W. Dankner.  Reduction of Respiratory Syncytial Virus Hospitalization Among Premature Infants and Infants with Bronchopulmonary Dysplasia Using Respiratory Syncytial Virus Immune Globulin Prophylaxis , 1997, Pediatrics.

[67]  A. Falsey,et al.  Respiratory syncytial virus and influenza A infections in the hospitalized elderly. , 1995, The Journal of infectious diseases.

[68]  D. Fulton,et al.  Prophylactic administration of respiratory syncytial virus immune globulin to high-risk infants and young children , 1994 .

[69]  E. Walsh,et al.  Protective activity of a human respiratory syncytial virus immune globulin prepared from donors screened by microneutralization assay. , 1992, The Journal of infectious diseases.

[70]  E. Walsh,et al.  Immunity to and frequency of reinfection with respiratory syncytial virus. , 1991, The Journal of infectious diseases.

[71]  W. P. Glezen,et al.  Risk of primary infection and reinfection with respiratory syncytial virus. , 1986, American journal of diseases of children.

[72]  A. Frank,et al.  Risk of respiratory syncytial virus infection for infants from low-income families in relationship to age, sex, ethnic group, and maternal antibody level. , 1981, The Journal of pediatrics.

[73]  E. H. Lennette,et al.  Field evaluation of a respiratory syncytial virus vaccine and a trivalent parainfluenza virus vaccine in a pediatric population. , 1969, American journal of epidemiology.

[74]  R. Chanock,et al.  An epidemiologic study of altered clinical reactivity to respiratory syncytial (RS) virus infection in children previously vaccinated with an inactivated RS virus vaccine. , 1969, American journal of epidemiology.

[75]  R. Chanock.  RECOVERY OF A NEW TYPE OF MYXOVIRUS FROM INFANTS WITH CROUP , 1957, Annals of the New York Academy of Sciences.

[76]  R. Karron,et al.  Respiratory syncytial virus vaccine research and development: World Health Organization technological roadmap and preferred product characteristics. , 2018, Vaccine.

[77]  D. M.,et al.  Respiratory Syncytial Virus and Recurrent Wheeze in Healthy Preterm Infants. , 2016, The New England journal of medicine.

[78]  W. Self,et al.  Community-acquired pneumonia requiring hospitalization among U.S. children. , 2015, The New England journal of medicine.

[79]  J. Crowe,et al.  Identification of an H-2D(b)-restricted CD8+ cytotoxic T lymphocyte epitope in the matrix protein of respiratory syncytial virus. , 2005, Virology.

[80]  Robert B Sim,et al.  Lung surfactant protein A provides a route of entry for respiratory syncytial virus into host cells. , 2000, Viral immunology.

[81]  R. E. Blount,et al.  Recovery of cytopathogenic agent from chimpanzees with coryza. , 1956, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.