Evaluation of a live, cold-passaged, temperature-sensitive, respiratory syncytial virus vaccine candidate in infancy

PF Wright, RA Karron, RB Belshe… - The Journal of …, 2000 - academic.oup.com
PF Wright, RA Karron, RB Belshe, J Thompson, JE Crowe Jr, TG Boyce, LL Halburnt…
The Journal of infectious diseases, 2000academic.oup.com
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-248/404vaccine 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 …
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-248/404vaccine 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-248/404vaccine candidate did not cause fever or lower respiratory tract illness. In the youngest infants, however, cpts-248/404was 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.
Oxford University Press