Evaluation of a live attenuated, cold-adapted parainfluenza virus type 3 vaccine in children

Area of Science:

• Virology
• Vaccinology
• Pediatrics

Background:

• Parainfluenza virus type 3 (PIV-3) is a significant cause of respiratory illness in infants and young children.
• Development of an effective PIV-3 vaccine is a public health priority.
• The CP18 strain was developed as a potential live attenuated PIV-3 vaccine candidate.

Purpose of the Study:

• To evaluate the safety and immunogenicity of the CP18 PIV-3 vaccine in infants and young children.
• To assess the infectivity of the CP18 PIV-3 vaccine in seropositive and seronegative children.
• To determine the optimal dose for a potential PIV-3 vaccine.

Main Methods:

• A double-blind, randomized, placebo-controlled study was conducted with 95 infants and young children.
• Participants received intranasal administration of either placebo or varying doses of the CP18 PIV-3 vaccine (10^5 or 10^6 TCID50).
• Infection was assessed by virus shedding and antibody response; clinical illness was monitored.

Main Results:

• Seropositive older children (41-124 months) did not become infected with 10^6 TCID50 of CP18 PIV-3.
• Infection occurred in 2/9 and 7/24 young seropositive children given 10^5 or 10^6 TCID50, respectively.
• All four seronegative young children given 10^6 TCID50 became infected, with two experiencing mild, febrile-free illness (rhinorrhea, wheezing).
• Vaccine virus spread to a sibling control in one instance without causing illness.
• The CP18 vaccine demonstrated attenuation compared to wild-type PIV-3, but was not fully attenuated.

Conclusions:

• The CP18 PIV-3 vaccine candidate demonstrated infectivity and induced an immune response.
• While generally well-tolerated, particularly in seropositive individuals, the vaccine caused infection and mild illness in some seronegative children.
• Additional attenuation of the CP18 PIV-3 vaccine is necessary to achieve a satisfactory safety profile for widespread use.