Safety and infectivity of two doses of live-attenuated recombinant cold-passaged human parainfluenza type 3 virus vaccine rHPIV3cp45 in HPIV3-seronegative young children

Janet A. Englund*, Ruth A. Karron, Coleen K. Cunningham, Philip La Russa, Ann Melvin, Ram Yogev, Ed Handelsman, George K. Siberry, Bhavanji Thumar, Elizabeth Schappell, Catherine V. Bull, Helen Y. Chu, Anne Schaap-Nutt, Ursula Buchholz, Peter L. Collins, Alexander C. Schmidt, Ann J. Melvin, Linda Marillo, Elizabeth Petzold, Paul SatoJoycelyn Thomas, Joan Dragavon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Background: Human parainfluenza virus type 3 (HPIV3) is a common cause of upper and lower respiratory tract illness in infants and young children. Live-attenuated cold-adapted HPIV3 vaccines have been evaluated in infants but a suitable interval for administration of a second dose of vaccine has not been defined. Methods: HPIV3-seronegative children between the ages of 6 and 36 months were randomized 2:1 in a blinded study to receive two doses of 105 TCID50 (50% tissue culture infectious dose) of live-attenuated, recombinant cold-passaged human PIV3 vaccine (rHPIV3cp45) or placebo 6 months apart. Serum antibody levels were assessed prior to and approximately 4-6 weeks after each dose. Vaccine virus infectivity, defined as detection of vaccine-HPIV3 in nasal wash and/or a≥4-fold rise in serum antibody titer, and reactogenicity were assessed on days 3, 7, and 14 following immunization. Results: Forty HPIV3-seronegative children (median age 13 months; range 6-35 months) were enrolled; 27 (68%) received vaccine and 13 (32%) received placebo. Infectivity was detected in 25 (96%) of 26 evaluable vaccinees following doses 1 and 9 of 26 subject (35%) following dose 2. Among those who shed virus, the median duration of viral shedding was 12 days (range 6-15 days) after dose 1 and 6 days (range 3-8 days) after dose 2, with a mean peak log10 viral titer of 3.4PFU/mL (SD: 1.0) after dose 1 compared to 1.5PFU/mL (SD: 0.92) after dose 2. Overall, reactogenicity was mild, with no difference in rates of fever and upper respiratory infection symptoms between vaccine and placebo groups. Conclusion: rHPIV3cp45 was immunogenic and well-tolerated in seronegative young children. A second dose administered 6 months after the initial dose was restricted in those previously infected with vaccine virus; however, the second dose boosted antibody responses and induced antibody responses in two previously uninfected children.

Original languageEnglish (US)
Pages (from-to)5706-5712
Number of pages7
JournalVaccine
Volume31
Issue number48
DOIs
StatePublished - Nov 19 2013

Keywords

  • Live-attenuated vaccine
  • Parainfluenza
  • Pediatric vaccine
  • Recombinant virus vaccine

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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