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Randomized Controlled Trial
. 2013 Nov 19;31(48):5706-12.
doi: 10.1016/j.vaccine.2013.09.046. Epub 2013 Oct 5.

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  1 , Ruth A Karron, Coleen K Cunningham, Philip Larussa, 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; International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1096 Study Group
Collaborators, Affiliations
Randomized Controlled Trial

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 et al. Vaccine. .

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 3.4 PFU/mL (SD: 1.0) after dose 1 compared to 1.5 PFU/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.

Keywords: Live-attenuated vaccine; Parainfluenza; Pediatric vaccine; Recombinant virus vaccine.

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Figures

Fig. 1
Fig. 1
The study design is depicted below. All vaccine recipients who participated in dose 2 of the study, received vaccine for dose 2. All placebo recipients received placebo for both dose 1 and dose 2. Abbreviations: D = study day; NW = collection of nasal wash; S = blood draw for collection of sera.
Fig. 2
Fig. 2
CONSORT participant flow diagram.
Fig. 3
Fig. 3
Reciprocal HAI antibody levels before and after dose 1 and dose 2 for all individual vaccine recipients.
See this image and copyright information in PMC

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