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Evaluation of a Live-Attenuated Human Parainfluenza Type 1 Vaccine in Adults and Children
Ruth A Karron1, Jocelyn San Mateo1, Bhagvanji Thumar1
1Center for Immunization Research, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Insights
A novel live-attenuated human parainfluenza virus type 1 (HPIV-1) vaccine showed limited replication in adults and seropositive children. However, it was insufficiently infectious for seronegative children, indicating overattenuation for the target population.
Area of Science:
- Virology
- Vaccinology
- Clinical Trials
Background:
- Human parainfluenza virus type 1 (HPIV-1) is a significant cause of respiratory illness in children.
- Development of an effective HPIV-1 vaccine is a public health priority.
- Live-attenuated vaccines are a promising strategy for HPIV-1 prevention.
Purpose of the Study:
- To evaluate the safety, tolerability, and immunogenicity of an experimental live-attenuated HPIV-1 vaccine (rHPIV-1/84/del 170/942A) in a phase I clinical trial.
- To assess vaccine replication in different populations: adults, HPIV-1-seropositive children, and HPIV-1-seronegative children.
- To determine the optimal attenuation level for a future HPIV-1 vaccine.
Main Methods:
- Phase I clinical trial involving sequential administration of rHPIV-1/84/del 170/942A to three distinct groups.
- Groups included healthy adults, children with prior HPIV-1 exposure (seropositive), and children without prior HPIV-1 exposure (seronegative).
- Assessment of viral replication, safety, and immune responses post-vaccination.
Main Results:
- The vaccine candidate rHPIV-1/84/del 170/942A demonstrated controlled replication in adults and HPIV-1-seropositive children.
- In HPIV-1-seronegative children, the target population, the vaccine was found to be overattenuated, showing insufficient infectivity and immunogenicity.
- The study identified a need for dose adjustment or further attenuation modification for effective vaccination in the primary target group.
Conclusions:
- The experimental live-attenuated HPIV-1 vaccine rHPIV-1/84/del 170/942A exhibited appropriate attenuation in adults and seropositive children.
- The vaccine was overattenuated for seronegative children, failing to elicit sufficient immune responses in this crucial demographic.
- Further research is needed to optimize the rHPIV-1/84/del 170/942A vaccine candidate for effective HPIV-1 prevention in the pediatric population.
Abstract:
We conducted a phase I clinical trial (clinicaltrials.gov identifier, NCT00641017) of the experimental live-attenuated human parainfluenza virus type 1 (HPIV-1) vaccine rHPIV-1/84/del 170/942A sequentially in 3 groups: adults, HPIV-1-seropositive children, and HPIV-1-seronegative children, the target population for vaccination. rHPIV-1/84/del 170/942A was appropriately restricted in replication in adults and HPIV-1-seropositive children but was overattenuated (ie, insufficiently infectious and immunogenic) for HPIV-1-seronegative children.
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