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Human parainfluenza virus type 1 immunization of infant mice protects from subsequent Sendai virus infection
M Sangster1, F S Smith, C Coleclough
1Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101, USA.
Insights
Infant mice vaccinated with human parainfluenza virus type 1 (hPIV-1) showed cross-reactive immunity against Sendai virus. This suggests Sendai virus could be a potential vaccine for infants against hPIV-1 infections.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Human parainfluenza virus type 1 (hPIV-1) causes severe respiratory illness, like croup, in infants, with no available vaccine.
- Sendai virus, a mouse parainfluenza virus, is the closest known relative to hPIV-1.
Purpose of the Study:
- To investigate the potential of using a nonpathogenic, xenotropic parainfluenza virus as a vaccine in infants.
- To assess the efficacy of hPIV-1 vaccination in infant mice against a subsequent Sendai virus challenge.
Main Methods:
- Infant mice (3-6 days old) were intranasally administered hPIV-1.
- Serum antibody ELISA and elispot analysis were used to detect virus-specific IgM and isotype-switched antibody-forming cells (AFC).
- Mice were challenged with Sendai virus 6-8 weeks post-vaccination and immune responses were analyzed.
Main Results:
- hPIV-1 vaccination elicited cross-reactive IgM and isotype-switched AFC responses to both hPIV-1 and Sendai virus.
- Primed infant mice, unlike controls, mounted robust IgM, IgG, and IgA responses upon Sendai virus challenge.
- The majority of hPIV-1 primed infant mice survived a lethal Sendai virus challenge, indicating protection.
Conclusions:
- The study supports the concept of using unmodified xenotropic Sendai virus as a potential vaccine for human infants against hPIV-1.
- Infant priming with hPIV-1 induced a unique IgM-dominant antibody-forming cell response crucial for protection.
- Cross-reactivity between hPIV-1 and Sendai virus offers a promising avenue for developing effective infant vaccines against hPIV-1 infections.
Abstract:
Human parainfluenza virus type 1 (hPIV-1) infections are a common cause of "croup" and hospitalizations among young children, yet no vaccine is yet available. Sendai virus (mouse PIV-1) is the closest known homologue of hPIV-1. Here we address the possibility of using a xenotropic, nonpathogenic PIV as a vaccine in infants, by assessing the efficacy of hPIV-1 vaccination of infant mice against a subsequent challenge with Sendai virus. hPIV-1 was administered intranasally to mice age 3-6 days and shown by serum antibody ELISA and elispot analysis to elicit virus-specific IgM and isotype-switched antibody-forming cells (AFC). The response was completely cross-reactive between hPIV-1 and Sendai virus. Mice were challenged with Sendai virus 6-8 weeks later and generated AFC and serum antibody responses composed of IgM, as well as IgG and IgA, unlike challenged, age-matched controls. The high IgM response among AFC was not seen in mice primed as adults with hPIV-1 and challenged with Sendai virus. The hPIV-1 priming of infant mice afforded protection, as the majority of these mice survived the lethal Sendai virus challenge, as did all adult primed animals. These data support the notion that the unmodified xenotropic Sendai virus might function effectively in human infants as a vaccine against hPIV-1.