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Updated: Sep 25, 2026

Intranasal Administration of Recombinant Influenza Vaccines in Chimeric Mouse Models to Study Mucosal Immunity
Published on: June 25, 2015
A live human parainfluenza type 3 virus vaccine is attenuated and immunogenic in young infants
Insights
A new intranasal parainfluenza type 3 virus (PIV-3) vaccine, cp-45, shows promise for preventing respiratory illness. This live attenuated vaccine is safe and immunogenic in infants as young as one month old.
Area of Science:
- Virology
- Vaccinology
- Pediatric Infectious Diseases
Background:
- Parainfluenza type 3 virus (PIV-3) is a significant cause of pediatric lower respiratory tract infections globally.
- Currently, no licensed PIV-3 vaccine is available to prevent these infections.
Purpose of the Study:
- To evaluate the safety, infectivity, immunogenicity, and phenotypic stability of a live attenuated cold-adapted (ca) and temperature-sensitive (ts) PIV-3 vaccine (cp-45).
- To assess the vaccine's efficacy in various age groups, including adults, seronegative children, and infants as young as one month old.
Main Methods:
- Sequential open-label and placebo-controlled, double-blind studies were conducted in 20 adults, 24 PIV-3-seropositive children, 52 PIV-3-seronegative infants and children, and 49 infants (1-2 months old).
- Intranasal administration of a single dose of cp-45 vaccine was used in adults and seropositive children, while seronegative children received higher doses.
- Infants received two doses of vaccine at 1- or 3-month intervals. Safety, infectivity, immunogenicity, and phenotypic stability were assessed.
Main Results:
- The cp-45 vaccine was well-tolerated across all age groups.
- Vaccine infection rates were high (94%) in seronegative children and infants.
- Antibody responses were detected, with IgA to hemagglutinin-neuraminidase being a key indicator in young infants. Temperature-sensitive intermediate (tsi) viruses were transient and not clinically significant. Cold-adapted revertants were not detected.
Conclusions:
- The cp-45 vaccine is appropriately attenuated and demonstrates immunogenicity in infants as young as one month.
- The findings support further development of the cp-45 vaccine for PIV-3 prevention.
Background:
Parainfluenza type 3 virus (PIV-3) infections cause lower respiratory tract illness in children throughout the world. A licensed PIV-3 vaccine is not yet available.
Methods:
A live attenuated cold-adapted (ca) and temperature-sensitive (ts) PIV-3 vaccine, designated cp-45, was evaluated sequentially in open label studies in 20 adults and in placebo-controlled, double blind studies in 24 PIV-3-seropositive children, 52 PIV-3-seronegative infants and children and 49 infants 1 to 2 months old. A single dose of this intranasal vaccine was evaluated in adults [106 plaque-forming units (pfu)] and seropositive children, and 104 and 105 pfu were evaluated in seronegative children. In the infant study, two 104 pfu doses of vaccine were administered at 1- or 3-month intervals. Safety, infectivity, immunogenicity and phenotypic stability of the vaccine were evaluated in all cohorts.
Results:
The cp-45 vaccine was well-tolerated in all age groups and infected 94% of vaccinated seronegative children and 94% of vaccinated infants. Although immunization with the first dose of cp-45 diminished the replication of a second dose in all infants, those immunized after 3 months shed vaccine virus more frequently than those immunized after 1 month (62% vs. 24%, respectively). Antibody responses to PIV-3 were readily detected in seronegative children with a variety of assays; however, the IgA response to the viral hemagglutinin-neuraminidase was the best measure of immunogenicity in young infants. Of 109 vaccine virus specimens recovered from nasal washes, 98 were ts and 11 were temperature-sensitive intermediate (tsi) viruses, with pinpoint plaques visible at 40 degrees C. tsi viruses appeared transiently at the time of peak viral replication, represented a very small proportion of the total virus shed and were not associated with changes in clinical status. ca revertants were not detected.
Conclusions:
The cp-45 vaccine is appropriately attenuated and immunogenic in infants as young as 1 month of age. Further development of this vaccine is warranted.
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