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Neonatal pneumococcal conjugate vaccine immunization primes T cells for preferential Th2 cytokine expression: a randomized controlled trial in Papua New Guinea.

van den Biggelaar AH, Richmond PC, Pomat WS, Phuanukoonnon S, Nadal-Sims MA, Devitt CJ, Siba PM, Lehmann D, Holt PG - Vaccine (2009)

Bottom Line: Neonatal 7vPCV priming (followed by a dose at 1 and 2 months of age) was associated with enhanced Th2, but not Th1, cytokine responses to CRM(197) compared to 7vPCV at 1 and 2 months of age only.T cell responses to non-7vPCV vaccine antigens were similar in all groups, but TLR-mediated IL-6 and IL-10 responses were enhanced in 7vPCV vaccinated compared to controls.Neonatal 7vPCV vaccination primes T cell responses with a polarization towards Th2 with no bystander effects on other T cell responses.

View Article: PubMed Central - PubMed

Affiliation: Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, PO Box 855, West Perth, WA 6872, Australia. Anitav@ichr.uwa.edu.au

ABSTRACT
The effects of neonatal immunization with 7-valent pneumococcal conjugate vaccine (7vPCV) on development of T-cell memory and general immune maturation were studied in a cohort of Papua New Guinean newborns. Neonatal 7vPCV priming (followed by a dose at 1 and 2 months of age) was associated with enhanced Th2, but not Th1, cytokine responses to CRM(197) compared to 7vPCV at 1 and 2 months of age only. T cell responses to non-7vPCV vaccine antigens were similar in all groups, but TLR-mediated IL-6 and IL-10 responses were enhanced in 7vPCV vaccinated compared to controls. Neonatal 7vPCV vaccination primes T cell responses with a polarization towards Th2 with no bystander effects on other T cell responses.

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TLR-mediated immune responses. PBMC of 3-month-old children in the neonatal (white bar), infant (grey bar) and control group (black bar) were stimulated in vitro with lipoteichoic acid (LTA) (neonatal n = 37; infant n = 39; control n = 33), polyinosinic–polycytidylic acid (Poly:IC) (neonatal n = 40; infant n = 38; control n = 34), lipopolysaccharide (LPS) (neonatal n = 42; infant n = 40, control n = 35) and oligonucleotide CpG (CpG) (neonatal n = 32; infant n = 34; control n = 27). Bars represent geometric means and standard errors of geometric means of ligand specific cytokine responses (minus background response).
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fig3: TLR-mediated immune responses. PBMC of 3-month-old children in the neonatal (white bar), infant (grey bar) and control group (black bar) were stimulated in vitro with lipoteichoic acid (LTA) (neonatal n = 37; infant n = 39; control n = 33), polyinosinic–polycytidylic acid (Poly:IC) (neonatal n = 40; infant n = 38; control n = 34), lipopolysaccharide (LPS) (neonatal n = 42; infant n = 40, control n = 35) and oligonucleotide CpG (CpG) (neonatal n = 32; infant n = 34; control n = 27). Bars represent geometric means and standard errors of geometric means of ligand specific cytokine responses (minus background response).

Mentions: Children in the neonatal and infant 7vPCV vaccination groups produced higher IL-10 and IL-6 responses to the TLR ligands LTA (TLR2) (IL-10, p = 0.006; IL-6, p = 0.053), poly:IC (TLR3) (IL-10, p = 0.015; IL-6, p = 0.049) and LPS (TLR4) (IL-10, p = 0.052; IL-6, p = 0.028) than the control group (Fig. 3). A similar trend was seen for TNF-α responses, but differences were not statistically significant. TLR-mediated IFN-γ responses were generally higher in the infant group, but this was only significant in response to CpG.


Neonatal pneumococcal conjugate vaccine immunization primes T cells for preferential Th2 cytokine expression: a randomized controlled trial in Papua New Guinea.

van den Biggelaar AH, Richmond PC, Pomat WS, Phuanukoonnon S, Nadal-Sims MA, Devitt CJ, Siba PM, Lehmann D, Holt PG - Vaccine (2009)

TLR-mediated immune responses. PBMC of 3-month-old children in the neonatal (white bar), infant (grey bar) and control group (black bar) were stimulated in vitro with lipoteichoic acid (LTA) (neonatal n = 37; infant n = 39; control n = 33), polyinosinic–polycytidylic acid (Poly:IC) (neonatal n = 40; infant n = 38; control n = 34), lipopolysaccharide (LPS) (neonatal n = 42; infant n = 40, control n = 35) and oligonucleotide CpG (CpG) (neonatal n = 32; infant n = 34; control n = 27). Bars represent geometric means and standard errors of geometric means of ligand specific cytokine responses (minus background response).
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Related In: Results  -  Collection

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fig3: TLR-mediated immune responses. PBMC of 3-month-old children in the neonatal (white bar), infant (grey bar) and control group (black bar) were stimulated in vitro with lipoteichoic acid (LTA) (neonatal n = 37; infant n = 39; control n = 33), polyinosinic–polycytidylic acid (Poly:IC) (neonatal n = 40; infant n = 38; control n = 34), lipopolysaccharide (LPS) (neonatal n = 42; infant n = 40, control n = 35) and oligonucleotide CpG (CpG) (neonatal n = 32; infant n = 34; control n = 27). Bars represent geometric means and standard errors of geometric means of ligand specific cytokine responses (minus background response).
Mentions: Children in the neonatal and infant 7vPCV vaccination groups produced higher IL-10 and IL-6 responses to the TLR ligands LTA (TLR2) (IL-10, p = 0.006; IL-6, p = 0.053), poly:IC (TLR3) (IL-10, p = 0.015; IL-6, p = 0.049) and LPS (TLR4) (IL-10, p = 0.052; IL-6, p = 0.028) than the control group (Fig. 3). A similar trend was seen for TNF-α responses, but differences were not statistically significant. TLR-mediated IFN-γ responses were generally higher in the infant group, but this was only significant in response to CpG.

Bottom Line: Neonatal 7vPCV priming (followed by a dose at 1 and 2 months of age) was associated with enhanced Th2, but not Th1, cytokine responses to CRM(197) compared to 7vPCV at 1 and 2 months of age only.T cell responses to non-7vPCV vaccine antigens were similar in all groups, but TLR-mediated IL-6 and IL-10 responses were enhanced in 7vPCV vaccinated compared to controls.Neonatal 7vPCV vaccination primes T cell responses with a polarization towards Th2 with no bystander effects on other T cell responses.

View Article: PubMed Central - PubMed

Affiliation: Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, PO Box 855, West Perth, WA 6872, Australia. Anitav@ichr.uwa.edu.au

ABSTRACT
The effects of neonatal immunization with 7-valent pneumococcal conjugate vaccine (7vPCV) on development of T-cell memory and general immune maturation were studied in a cohort of Papua New Guinean newborns. Neonatal 7vPCV priming (followed by a dose at 1 and 2 months of age) was associated with enhanced Th2, but not Th1, cytokine responses to CRM(197) compared to 7vPCV at 1 and 2 months of age only. T cell responses to non-7vPCV vaccine antigens were similar in all groups, but TLR-mediated IL-6 and IL-10 responses were enhanced in 7vPCV vaccinated compared to controls. Neonatal 7vPCV vaccination primes T cell responses with a polarization towards Th2 with no bystander effects on other T cell responses.

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