Evaluation of a Live, Cold‐Passaged, Temperature‐Sensitive, Respiratory Syncytial Virus Vaccine Candidate in Infancy

TLDR

A live‑attenuated, intranasal RSV candidate vaccine, cpts‑248/404, was evaluated in phase 1 trials involving 114 children, including 37 infants aged 1–2 months. The vaccine was infectious at 10^4–10^5 PFU, induced broad immunity in children over 6 months, elicited IgA responses in 1–2‑month olds without neutralizing activity, showed limited shedding after a second dose, provided preliminary protection against symptomatic disease, caused no fever or lower respiratory illness, but was poorly tolerated in the youngest infants due to upper respiratory congestion, prompting further attenuation.

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.