Progress in the development of human parainfluenza virus vaccines

In children under 5 years of age, human parainfluenza viruses (HPIVs) as a group are the second most common etiology of acute respiratory illness leading to hospitalization, surpassed only by respiratory syncytial virus but ahead of influenza viruses. Using reverse genetics systems for HPIV serotypes 1, 2 and 3 (HPIV1, 2 and 3), several live-attenuated HPIVs have been generated and evaluated as intranasal vaccines in adults and in children. Two vaccines against HPIV3 were found to be well tolerated, infectious and immunogenic in Phase I trials in HPIV3-seronegative infants and children and should progress to proof-of-concept trials. Vaccines against HPIV1 and HPIV2 are less advanced and have just entered pediatric trials.

[1]  R. Chanock,et al.  Passive transfer of respiratory syncytial virus (RSV) antiserum suppresses the immune response to the RSV fusion (F) and large (G) glycoproteins expressed by recombinant vaccinia viruses , 1988, Journal of virology.

[2]  P. Collins,et al.  Identification of Mutations Contributing to the Temperature-Sensitive, Cold-Adapted, and Attenuation Phenotypes of the Live-Attenuated Cold-Passage 45 (cp45) Human Parainfluenza Virus 3 Candidate Vaccine , 1999, Journal of Virology.

[3]  Alan D. Roberts,et al.  The route of priming influences the ability of respiratory virus–specific memory CD8+ T cells to be activated by residual antigen , 2010, The Journal of experimental medicine.

[4]  T. Cherian,et al.  Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates , 2009, The Lancet.

[5]  Brian R. Murphy,et al.  Role of Interferon in the Replication of Human Parainfluenza Virus Type 1 Wild Type and Mutant Viruses in Human Ciliated Airway Epithelium , 2008, Journal of Virology.

[6]  M. Schumacher,et al.  Prospective population-based study of viral lower respiratory tract infections in children under 3 years of age (the PRI.DE study) , 2004, European Journal of Pediatrics.

[7]  B. Murphy,et al.  Attenuating mutations in the P/C gene of human parainfluenza virus type 1 (HPIV1) vaccine candidates abrogate the inhibition of both induction and signaling of type I interferon (IFN) by wild-type HPIV1. , 2006, Virology.

[8]  B. Murphy.  Current approaches to the development of vaccines effective against parainfluenza viruses. , 1988, Bulletin of the World Health Organization.

[9]  Kelly J. Henrickson.  Parainfluenza Viruses , 2003, Clinical Microbiology Reviews.

[10]  R. Karron,et al.  A live human parainfluenza type 3 virus vaccine is attenuated and immunogenic in young infants , 2003, The Pediatric infectious disease journal.

[11]  J. Crowe,et al.  Influence of maternal antibodies on neonatal immunization against respiratory viruses. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[12]  R. Spaete,et al.  Parainfluenza Virus Type 3 Expressing the Native or Soluble Fusion (F) Protein of Respiratory Syncytial Virus (RSV) Confers Protection from RSV Infection in African Green Monkeys , 2004, Journal of Virology.

[13]  R. Maziarz,et al.  Control of an Outbreak of Human Parainfluenza Virus 3 in Hematopoietic Stem Cell Transplant Recipients , 2009, Biology of Blood and Marrow Transplantation.

[14]  B. Murphy,et al.  Live-attenuated virus vaccines for respiratory syncytial and parainfluenza viruses: applications of reverse genetics. , 2002, The Journal of clinical investigation.

[15]  B. Murphy,et al.  Introducing point and deletion mutations into the P/C gene of human parainfluenza virus type 1 (HPIV1) by reverse genetics generates attenuated and efficacious vaccine candidates. , 2006, Vaccine.

[16]  B. Murphy,et al.  Generation of Recombinant Human Parainfluenza Virus Type 1 Vaccine Candidates by Importation of Temperature-Sensitive and Attenuating Mutations from Heterologous Paramyxoviruses , 2004, Journal of Virology.

[17]  K. Edwards,et al.  Human Metapneumovirus Infection among Children Hospitalized with Acute Respiratory Illness , 2004, Emerging infectious diseases.

[18]  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.

[19]  A. A. Haller,et al.  Expression of the Surface Glycoproteins of Human Parainfluenza Virus Type 3 by Bovine Parainfluenza Virus Type 3, a Novel Attenuated Virus Vaccine Vector , 2000, Journal of Virology.

[20]  Lori Hutwagner,et al.  Seasonal trends of human parainfluenza viral infections: United States, 1990-2004. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[21]  R. Chanock,et al.  Immunoglobulins in serum and nasal secretions following infection with type 1 parainfluenza virus and injection of inactivated vaccines. , 1967, Journal of immunology.

[22]  W. Bellini,et al.  Maternal antibody inhibits both cellular and humoral immunity in response to measles vaccination at birth. , 2006, Virology.

[23]  B. Murphy,et al.  Recovery of a Fully Viable Chimeric Human Parainfluenza Virus (PIV) Type 3 in Which the Hemagglutinin-Neuraminidase and Fusion Glycoproteins Have Been Replaced by Those of PIV Type 1 , 1998, Journal of Virology.

[24]  B. Murphy,et al.  Attenuation and efficacy of human parainfluenza virus type 1 (HPIV1) vaccine candidates containing stabilized mutations in the P/C and L genes , 2007, Virology Journal.

[25]  R. Karron,et al.  A live human parainfluenza type 3 virus vaccine is attenuated and immunogenic in healthy infants and children. , 1995, The Journal of infectious diseases.

[26]  Michael J. Holtzman,et al.  Melanoma Differentiation-Associated Gene 5 (MDA5) Is Involved in the Innate Immune Response to Paramyxoviridae Infection In Vivo , 2010, PLoS pathogens.

[27]  The recombinant chimeric human parainfluenza virus type 1 vaccine candidate, rHPIV3-1cp45, is attenuated, immunogenic, and protective in African green monkeys. , 2002, Vaccine.

[28]  R. Tedder,et al.  Molecular Investigations of an Outbreak of Parainfluenza Virus Type 3 and Respiratory Syncytial Virus Infections in a Hematology Unit , 2007, Journal of Clinical Microbiology.

[29]  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.

[30]  R. Karron,et al.  Identification of a recombinant live attenuated respiratory syncytial virus vaccine candidate that is highly attenuated in infants. , 2005, The Journal of infectious diseases.

[31]  M. St. Claire,et al.  The Two Major Human Metapneumovirus Genetic Lineages Are Highly Related Antigenically, and the Fusion (F) Protein Is a Major Contributor to This Antigenic Relatedness , 2004, Journal of Virology.

[32]  Brian R. Murphy,et al.  The Genome Length of Human Parainfluenza Virus Type 2 Follows the Rule of Six, and Recombinant Viruses Recovered from Non-Polyhexameric-Length Antigenomic cDNAs Contain a Biased Distribution of Correcting Mutations , 2003, Journal of Virology.

[33]  P. Jewett,et al.  Epidemiology and clinical impact of parainfluenza virus infections in otherwise healthy infants and young children < 5 years old. , 1997, The Journal of infectious diseases.

[34]  B. Murphy,et al.  Expression of the F and HN glycoproteins of human parainfluenza virus type 3 by recombinant vaccinia viruses: contributions of the individual proteins to host immunity , 1987, Journal of virology.

[35]  K. O'Brien,et al.  Young infants can develop protective levels of neutralizing antibody after infection with respiratory syncytial virus. , 2008, The Journal of infectious diseases.

[36]  B. Murphy,et al.  Respiratory syncytial virus: reverse genetics and vaccine strategies. , 2002, Virology.

[37]  R. Karron,et al.  Evaluation of a live, cold-passaged, temperature-sensitive, respiratory syncytial virus vaccine candidate in infancy. , 2000, The Journal of infectious diseases.

[38]  M. St. Claire,et al.  Recombinant human parainfluenza virus type 2 vaccine candidates containing a 3' genomic promoter mutation and L polymerase mutations are attenuated and protective in non-human primates. , 2007, Vaccine.

[39]  J. Shenep,et al.  Safety and immunogenicity of intranasal murine parainfluenza virus type 1 (Sendai virus) in healthy human adults. , 2004, Vaccine.

[40]  M. St. Claire,et al.  Mucosal Immunization of Rhesus Monkeys against Respiratory Syncytial Virus Subgroups A and B and Human Parainfluenza Virus Type 3 by Using a Live cDNA-Derived Vaccine Based on a Host Range-Attenuated Bovine Parainfluenza Virus Type 3 Vector Backbone , 2002, Journal of Virology.

[41]  R. Holman,et al.  Pediatric hospitalizations for croup (laryngotracheobronchitis): biennial increases associated with human parainfluenza virus 1 epidemics. , 1997, The Journal of infectious diseases.

[42]  T. Cherian,et al.  Burden of disease caused by Haemophilus influenzae type b in children younger than 5 years: global estimates , 2009, The Lancet.

[43]  R. Karron,et al.  Evaluation of a live attenuated bovine parainfluenza type 3 vaccine in two- to six-month-old infants. , 1996, The Pediatric infectious disease journal.

[44]  R. Karron,et al.  Addition of a Missense Mutation Present in the L Gene of Respiratory Syncytial Virus (RSV) cpts530/1030 to RSV Vaccine Candidate cpts248/404 Increases Its Attenuation and Temperature Sensitivity , 1999, Journal of Virology.

[45]  B. Murphy,et al.  Human parainfluenza virus type I (HPIV1) vaccine candidates designed by reverse genetics are attenuated and efficacious in African green monkeys. , 2005, Vaccine.

[46]  M. St. Claire,et al.  Determinants of the Host Range Restriction of Replication of Bovine Parainfluenza Virus Type 3 in Rhesus Monkeys Are Polygenic , 2003, Journal of Virology.

[47]  J. Crowe,et al.  Immunology of viral respiratory tract infection in infancy. , 2003, Paediatric respiratory reviews.

[48]  R. Belshe,et al.  Cold adaptation of parainfluenza virus type 3: Induction of three phenotypic markers , 1982, Journal of medical virology.

[49]  W. P. Glezen,et al.  Parainfluenza virus type 3: seasonality and risk of infection and reinfection in young children. , 1984, The Journal of infectious diseases.

[50]  B. Murphy,et al.  Recovery of infectious human parainfluenza virus type 3 from cDNA. , 1997, Virology.

[51]  B. Murphy,et al.  Three Amino Acid Substitutions in the L Protein of the Human Parainfluenza Virus Type 3 cp45 Live Attenuated Vaccine Candidate Contribute to Its Temperature-Sensitive and Attenuation Phenotypes , 1998, Journal of Virology.

[52]  R. Douglas,et al.  Interferon production in children with respiratory syncytial, influenza, and parainfluenza virus infections. , 1978, The Journal of pediatrics.

[53]  M. Uchikawa,et al.  Receptor Specificities of Human Respiroviruses , 2001, Journal of Virology.

[54]  G. Gerna,et al.  Multicluster nosocomial outbreak of parainfluenza virus type 3 infection in a pediatric oncohematology unit: a phylogenetic study , 2009, Haematologica.

[55]  B. Murphy,et al.  Sequence Analysis of the Washington/1964 Strain of Human Parainfluenza Virus Type 1 (HPIV1) and Recovery and Characterization of Wild-Type Recombinant HPIV1 Produced by Reverse Genetics , 2004, Virus Genes.

[56]  G. Losonsky,et al.  PHASE-I STUDY MEDI-534, OF A LIVE, ATTENUATED INTRANASAL VACCINE AGAINST RESPIRATORY SYNCYTIAL VIRUS AND PARAINFLUENZA-3 VIRUS IN SEROPOSITIVE CHILDREN , 2009, The Pediatric infectious disease journal.

[57]  B. Murphy,et al.  Growth restriction of an experimental live attenuated human parainfluenza virus type 2 vaccine in human ciliated airway epithelium in vitro parallels attenuation in African green monkeys , 2010, Vaccine.

[58]  B. Murphy,et al.  Comparison of identical temperature-sensitive mutations in the L polymerase proteins of sendai and parainfluenza3 viruses. , 2000, Virology.

[59]  C. Berek,et al.  The Postnatal Maturation of the Immunoglobulin Heavy Chain IgG Repertoire in Human Preterm Neonates Is Slower than in Term Neonates1 , 2007, The Journal of Immunology.

[60]  M. Boeckh,et al.  Prolonged outbreak of human parainfluenza virus 3 infection in a stem cell transplant outpatient department: insights from molecular epidemiologic analysis. , 2004, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[61]  J. McAuliffe,et al.  Bovine Parainfluenza Virus Type 3 (BPIV3) Fusion and Hemagglutinin-Neuraminidase Glycoproteins Make an Important Contribution to the Restricted Replication of BPIV3 in Primates , 2000, Journal of Virology.

[62]  S. Madhi,et al.  Evaluation of combined live, attenuated respiratory syncytial virus and parainfluenza 3 virus vaccines in infants and young children. , 2004, The Journal of infectious diseases.

[63]  C. Mathers,et al.  Global, regional, and national causes of child mortality in 2008: a systematic analysis , 2010, The Lancet.

[64]  K. Poehling,et al.  Impact of a school-based influenza immunization program on disease burden: comparison of two Tennessee counties. , 2009, Vaccine.

[65]  P. Collins,et al.  Infection of Ciliated Cells by Human Parainfluenza Virus Type 3 in an In Vitro Model of Human Airway Epithelium , 2005, Journal of Virology.

[66]  B. Murphy,et al.  Codon Substitution Mutations at Two Positions in the L Polymerase Protein of Human Parainfluenza Virus Type 1 Yield Viruses with a Spectrum of Attenuation In Vivo and Increased Phenotypic Stability In Vitro , 2004, Journal of Virology.

[67]  R. Karron,et al.  Severe respiratory syncytial virus disease in Alaska native children. RSV Alaska Study Group. , 1999, The Journal of infectious diseases.

[68]  S. Madhi,et al.  Transmissibility, infectivity and immunogenicity of a live human parainfluenza type 3 virus vaccine (HPIV3cp45) among susceptible infants and toddlers. , 2006, Vaccine.

[69]  G. Jackson,et al.  Neutralizing activity in nasal secretions and serum in resistance of volunteers to parainfluenza virus type 2. , 1968, Journal of immunology.

[70]  B. Murphy,et al.  Recombinant Bovine/Human Parainfluenza Virus Type 3 (B/HPIV3) Expressing the Respiratory Syncytial Virus (RSV) G and F Proteins Can Be Used To Achieve Simultaneous Mucosal Immunization against RSV and HPIV3 , 2001, Journal of Virology.

[71]  R. Karron,et al.  A bovine parainfluenza virus type 3 vaccine is safe and immunogenic in early infancy. , 2005, The Journal of infectious diseases.

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

[73]  B. Murphy,et al.  Attenuation of bovine parainfluenza virus type 3 in nonhuman primates and its ability to confer immunity to human parainfluenza virus type 3 challenge. , 1988, The Journal of infectious diseases.

[74]  R. Purcell,et al.  Protective effect of antibody to parainfluenza type 1 virus. , 1966, The New England journal of medicine.

[75]  B. Murphy,et al.  A novel human parainfluenza virus type 1 (HPIV1) with separated P and C genes is useful for generating C gene mutants for evaluation as live-attenuated virus vaccine candidates. , 2010, Vaccine.

[76]  K. Poehling,et al.  Parainfluenza virus infection of young children: estimates of the population-based burden of hospitalization. , 2009, The Journal of pediatrics.

[77]  R. Jaenisch,et al.  Delayed clearance of Sendai virus in mice lacking class I MHC-restricted CD8+ T cells. , 1992, Journal of immunology.

[78]  B. Murphy,et al.  Live-attenuated intranasal parainfluenza virus type 2 vaccine candidates developed by reverse genetics containing L polymerase protein mutations imported from heterologous paramyxoviruses. , 2005, Vaccine.

[79]  S. Akira,et al.  The C Proteins of Human Parainfluenza Virus Type 1 Limit Double-Stranded RNA Accumulation That Would Otherwise Trigger Activation of MDA5 and Protein Kinase R , 2010, Journal of Virology.

[80]  R. Karron,et al.  Phase 2 evaluation of parainfluenza type 3 cold passage mutant 45 live attenuated vaccine in healthy children 6-18 months old. , 2004, The Journal of infectious diseases.

[81]  D. Woodland,et al.  CD4+ T Cell Priming Accelerates the Clearance of Sendai Virus in Mice, but Has a Negative Effect on CD8+ T Cell Memory1 , 2000, The Journal of Immunology.

[82]  W. Mitzner,et al.  Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease , 2009, Nature Medicine.

[83]  B. Murphy,et al.  The two amino acid substitutions in the L protein of cpts530/1009, a live-attenuated respiratory syncytial virus candidate vaccine, are independent temperature-sensitive and attenuation mutations. , 1999, Vaccine.

[84]  B. Murphy,et al.  The C Proteins of Human Parainfluenza Virus Type 1 (HPIV1) Control the Transcription of a Broad Array of Cellular Genes That Would Otherwise Respond to HPIV1 Infection , 2008, Journal of Virology.

[85]  D. Kwiatkowski,et al.  Genetic variation at the IL10 gene locus is associated with severity of respiratory syncytial virus bronchiolitis. , 2005, The Journal of infectious diseases.

[86]  Brett A. McKinney,et al.  Functional Maturation of the Human Antibody Response to Rotavirus1 , 2008, The Journal of Immunology.

[87]  P. Doherty,et al.  Clearance of Sendai virus by CD8+ T cells requires direct targeting to virus‐infected epithelium , 1995, European journal of immunology.

[88]  P. Cane,et al.  Viral etiology of severe pneumonia among Kenyan infants and children. , 2010, JAMA.

[89]  R. Walker,et al.  Development of a PIV-vectored RSV vaccine: preclinical evaluation of safety, toxicity, and enhanced disease and initial clinical testing in healthy adults. , 2008, Vaccine.

[90]  R. Chanock,et al.  Current approaches to the development of vaccines effective against parainfluenza and respiratory syncytial viruses. , 1988, Virus research.

[91]  R. Karron,et al.  The absence of enhanced disease with wild type respiratory syncytial virus infection occurring after receipt of live, attenuated, respiratory syncytial virus vaccines. , 2007, Vaccine.

[92]  O. Ramilo,et al.  Reduction of respiratory syncytial virus (RSV) in tracheal aspirates in intubated infants by use of humanized monoclonal antibody to RSV F protein. , 1998, The Journal of infectious diseases.

[93]  B. Murphy,et al.  The Major Attenuating Mutations of the Respiratory Syncytial Virus Vaccine Candidate cpts530/1009 Specify Temperature-Sensitive Defects in Transcription and Replication and a Non-Temperature-Sensitive Alteration in mRNA Termination , 1999, Journal of Virology.

[94]  D. Voaklander,et al.  Croup presentations to emergency departments in Alberta, Canada: A large population‐based study , 2010, Pediatric pulmonology.

[95]  K. Poehling,et al.  The burden of respiratory syncytial virus infection in young children. , 2009, The New England journal of medicine.

[96]  Y. Ito,et al.  Recovery of infectious human parainfluenza type 2 virus from cDNA clones and properties of the defective virus without V-specific cysteine-rich domain. , 2001, Virology.

[97]  H. Balfour,et al.  Parainfluenza virus respiratory infection after bone marrow transplantation. , 1992, The New England journal of medicine.