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An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
Evaluation of a live, cold-passaged, temperature-sensitive, respiratory syncytial virus vaccine candidate in infancy
P F Wright1, R A Karron, R B Belshe
1Division of Infectious Disease, Dept. of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. peter.wright@mcmail.vanderbilt.edu
Insights
A live-attenuated intranasal respiratory syncytial virus (RSV) vaccine showed promise in children over 6 months but caused congestion in infants. Modifications are needed for a safe infant RSV vaccine.
Area of Science:
- Vaccinology
- Virology
- Pediatric Infectious Diseases
Background:
- Respiratory Syncytial Virus (RSV) poses a significant health risk to infants and young children.
- Developing safe and effective RSV vaccines, particularly for the youngest infants, remains a critical public health goal.
Purpose of the Study:
- To evaluate the safety, immunogenicity, and preliminary efficacy of a live-attenuated intranasal RSV vaccine candidate (cpts-248/404) in children, including young infants.
Main Methods:
- Phase 1 clinical trial involving 114 children, with a subset of 37 infants aged 1-2 months.
- Assessment of vaccine infectiousness, viral shedding, and host immune responses (serum and nasal antibodies).
- Evaluation of clinical outcomes, including fever, lower respiratory tract illness, and protection against symptomatic disease upon natural reexposure.
Main Results:
- The cpts-248/404 vaccine was infectious and broadly immunogenic in children older than 6 months.
- In infants aged 1-2 months, immune responses were IgA-dominant, targeted the RSV G protein, and lacked neutralizing activity.
- While showing restricted shedding and potential protection in older children, the vaccine caused upper respiratory tract congestion in the youngest infants, deeming it unacceptable.
Conclusions:
- The cpts-248/404 vaccine candidate demonstrates potential but requires further attenuation for safe use in the youngest infants.
- Additional attenuating mutations will be incorporated into the RSV vaccine for improved tolerability in infants.
- Further research is needed to optimize live-attenuated RSV vaccines for infant populations.
Abstract:
A live-attenuated, intranasal respiratory syncytial virus (RSV) candidate vaccine, cpts-248/404, was tested in phase 1 trials in 114 children, including 37 1-2-month-old infants-a target age for RSV vaccines. The cpts-248/404 vaccine was infectious at 104 and 105 plaque-forming units in RSV-naive children and was broadly immunogenic in children >6 months old. Serum and nasal antibody responses in 1-2 month olds were restricted to IgA, had a dominant response to RSV G protein, and had no increase in neutralizing activity. Nevertheless, there was restricted virus shedding on challenge with a second vaccine dose and preliminary evidence for protection from symptomatic disease on natural reexposure. The cpts-248/404 vaccine candidate did not cause fever or lower respiratory tract illness. In the youngest infants, however, cpts-248/404 was unacceptable because of upper respiratory tract congestion associated with peak virus recovery. A live attenuated RSV vaccine for the youngest infant will use cpts-248/404 modified by additional attenuating mutations.
