Evaluation of two chimeric bovine-human parainfluenza virus type 3 vaccines in infants and young children

Ruth A Karron, Bhagvanji Thumar, Elizabeth Schappell, Sonja Surman, Brian R Murphy, Peter L Collins, Alexander C Schmidt, Ruth A Karron, Bhagvanji Thumar, Elizabeth Schappell, Sonja Surman, Brian R Murphy, Peter L Collins, Alexander C Schmidt

Abstract

Human parainfluenza virus type 3 (HPIV3) is an important cause of lower respiratory tract illness in children, yet a licensed vaccine or antiviral drug is not available. We evaluated the safety, tolerability, infectivity, and immunogenicity of two intranasal, live-attenuated HPIV3 vaccines, designated rHPIV3-N(B) and rB/HPIV3, that were cDNA-derived chimeras of HPIV3 and bovine PIV3 (BPIV3). These were evaluated in adults, HPIV3 seropositive children, and HPIV3 seronegative children. A total of 112 subjects participated in these studies. Both rB/HPIV3 and rHPIV3-N(B) were highly restricted in replication in adults and seropositive children but readily infected seronegative children, who shed mean peak virus titers of 10(2.8) vs. 10(3.7)pfu/mL, respectively. Although rB/HPIV3 was more restricted in replication in seronegative children than rHPIV3-N(B), it induced significantly higher titers of hemagglutination inhibition (HAI) antibodies against HPIV3. Taken together, these data suggest that the rB/HPIV3 vaccine is the preferred candidate for further clinical development.

Copyright © 2012. Published by Elsevier Ltd.

Figures

Fig. 1
Fig. 1
Enrollment of adults, HPIV3 seropositive, and HPIV3 seronegative children in phase I clinical trials of the rHPIV3-NB and the rB/HPIV3 vaccines. As described in Section 2, adults were enrolled in open-label trials and children were enrolled in placebo-controlled trials. For each vaccine, studies were performed sequentially in adults, HPIV3 seropositive children, and HPIV3 seronegative children. A dose-escalation study was performed in the seronegative cohorts of children receiving rHPIV3-NB because the vaccine was insufficiently infectious at a dose of 105 TCID50. No subjects withdrew from this study. Additional details are provided in the text.
Fig. 2
Fig. 2
Quantitation of vaccine virus shedding in nasal washes from HPIV3 seronegative recipients of 105.0 TCID50 of either rHPIV3-NB or rB/HPIV3. Means and standard deviations of log10 titers are shown for those who shed vaccine virus. 0.6 log10 pfu/mL represents the limit of detection of the assay.

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Source: PubMed

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