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Age-related development of human memory T-helper and B-cell responses toward parainfluenza virus type-1
F S Smith1, A Portner, R J Leggiadro
1Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Insights
Immune memory responses to human parainfluenza-1 virus (hPIV-1) are poor in young children, contrary to theories linking robust immunity to severe illness. Findings suggest memory correlates with better outcomes and identifies Sendai virus for vaccine development.
Area of Science:
- Virology
- Immunology
- Pediatric Respiratory Illness
Background:
- Human parainfluenza-1 virus (hPIV-1) causes significant respiratory illness in children, with milder symptoms in adults.
- Disease severity differences may stem from varying immune memory responses between children and adults.
- Existing theories propose either inferior pediatric immunity or exaggerated pediatric immune responses causing severe hPIV-1 symptoms.
Purpose of the Study:
- To investigate age-related differences in human parainfluenza-1 virus (hPIV-1)-specific T-helper (TH) and B-cell memory responses.
- To test the hypothesis that robust pediatric immune responses contribute to hPIV-1 disease severity.
- To explore potential cross-reactivity with other viruses and identify vaccine candidates.
Main Methods:
- Analysis of hPIV-1-specific B-cell and class-II restricted TH-cell proliferative responses in individuals across different age groups.
- Assessment of TH-cell recognition of internal viral proteins and the hemagglutinin-neuraminidase glycoprotein.
- Evaluation of immune response cross-reactivity with Sendai virus.
Main Results:
- Adults exhibited robust hPIV-1-specific B-cell and TH-cell responses, recognizing both internal and external viral components.
- Immune responses demonstrated significant cross-reactivity with Sendai virus.
- Young children, including those hospitalized with hPIV-1-induced croup, showed markedly poor memory B-cell and TH-cell responses.
Conclusions:
- The study refutes the theory that naturally induced hPIV-1 memory responses cause respiratory illness.
- Results indicate a positive correlation between immune memory and favorable clinical outcomes in hPIV-1 infections.
- Sendai virus emerges as a promising candidate for developing an hPIV-1 vaccine.
Abstract:
Human parainfluenza-1 virus (hPIV-1) infections are a major cause of respiratory illness in young children. While children and adults are each susceptible to hPIV-1 infection, the clinical symptoms in adults are mild and hospitalizations are rare. One explanation for the differences in disease severity is that immune memory responses are simply inferior in children as compared to adults and cannot counter virus growth. Alternatively, it has been suggested that immune (particularly T-helper (TH) cell) responses toward respiratory viruses are superior in children versus older individuals, and that these responses contribute to, rather than protect from, disease symptoms. As a test of these possibilities, we analyzed hPIV-1-specific T-helper (TH) and B-cell memory responses among individuals of various ages, including children hospitalized with hPIV-1-induced croup. Experiments revealed: (1) hPIV-1-specific B-cell and class-II restricted TH-cell proliferative responses were present in all tested adults. (2) TH-cells responded to internal viral proteins as well as to the external glycoprotein, hemagglutinin-neuraminidase. (3) Immune responses were highly cross-reactive with Sendai virus. (4) Memory B-cell and TH-cell responses were extremely poor in young children, inclusive of children tested upon hospital entry for hPIV-1-induced croup. In total, results did not support the theory that naturally induced hPIV-specific memory responses cause respiratory illness. Rather, results showed a correlation between memory and a good clinical outcome and highlighted Sendai virus as a strong candidate for an hPIV-1 vaccine.