Nematode-induced interference with the anti-Plasmodium CD8+ T-cell response can be overcome by optimizing antigen administration.
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Nematode-induced interference with the anti-Plasmodium CD8+ T-cell response can be overcome by optimizing antigen administration. / Kolbaum, Julia; Tartz, Susanne; Hartmann, Wiebke; Helm, Susanne; Nagel, Andreas; Heussler, Volker; Sebo, Peter; Fleischer, Bernhard; Jacobs, Thomas; Breloer, Minka.
In: EUR J IMMUNOL, Vol. 42, No. 4, 4, 2012, p. 890-900.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Nematode-induced interference with the anti-Plasmodium CD8+ T-cell response can be overcome by optimizing antigen administration.
AU - Kolbaum, Julia
AU - Tartz, Susanne
AU - Hartmann, Wiebke
AU - Helm, Susanne
AU - Nagel, Andreas
AU - Heussler, Volker
AU - Sebo, Peter
AU - Fleischer, Bernhard
AU - Jacobs, Thomas
AU - Breloer, Minka
PY - 2012
Y1 - 2012
N2 - Malaria is still responsible for up to 1 million deaths per year worldwide, highlighting the need for protective malaria vaccines. Helminth infections that are prevalent in malaria endemic areas can modulate immune responses of the host. Here we show that Strongy-Ioides ratti, a gut-dwelling nematode that causes transient infections, did not change the efficacy of vaccination against Plasmodium berghei. An ongoing infection with Litomosoides sigmodontis, a tissue-dwelling filaria that induces chronic infections in BALB/c mice, significantly interfered with vaccination efficacy. The induction of P. berghei circumspor-ozoite protein (CSP)-specific CD8(+) T cells, achieved by a single immunization with a CSP fusion protein, was diminished in L. sigmodontis-infected mice. This modulation was reflected by reduced frequencies of CSP-specific CD8(+) T cells, reduced CSP-specific IFN-y and TNF-a production, reduced CSP-specific cytotoxicity, and reduced protection against P. berghei challenge infection. Implementation of a more potent vaccine regime, by first priming with CSP-expressing recombinant live Salmonella prior to CSP fusion protein immunization, restored induction of CSP-specific CD8(+) T cells and conferred almost sterile immunity to P. berghei challenge infection also in L. sigmodontis-infected mice. In summary, we show that appropriate vaccination regimes can overcome helminth-induced interference with vaccination efficacy.
AB - Malaria is still responsible for up to 1 million deaths per year worldwide, highlighting the need for protective malaria vaccines. Helminth infections that are prevalent in malaria endemic areas can modulate immune responses of the host. Here we show that Strongy-Ioides ratti, a gut-dwelling nematode that causes transient infections, did not change the efficacy of vaccination against Plasmodium berghei. An ongoing infection with Litomosoides sigmodontis, a tissue-dwelling filaria that induces chronic infections in BALB/c mice, significantly interfered with vaccination efficacy. The induction of P. berghei circumspor-ozoite protein (CSP)-specific CD8(+) T cells, achieved by a single immunization with a CSP fusion protein, was diminished in L. sigmodontis-infected mice. This modulation was reflected by reduced frequencies of CSP-specific CD8(+) T cells, reduced CSP-specific IFN-y and TNF-a production, reduced CSP-specific cytotoxicity, and reduced protection against P. berghei challenge infection. Implementation of a more potent vaccine regime, by first priming with CSP-expressing recombinant live Salmonella prior to CSP fusion protein immunization, restored induction of CSP-specific CD8(+) T cells and conferred almost sterile immunity to P. berghei challenge infection also in L. sigmodontis-infected mice. In summary, we show that appropriate vaccination regimes can overcome helminth-induced interference with vaccination efficacy.
KW - Animals
KW - Mice
KW - Mice, Inbred BALB C
KW - Rats
KW - Rats, Wistar
KW - Interferon-gamma/immunology
KW - Immunization
KW - Strongyloides ratti/immunology
KW - Sigmodontinae
KW - CD8-Positive T-Lymphocytes/immunology
KW - Antigens, Protozoan/immunology/pharmacology
KW - Filariasis/immunology
KW - Filarioidea/immunology
KW - Malaria/immunology
KW - Plasmodium berghei/immunology
KW - Protozoan Proteins/immunology/pharmacology
KW - Salmonella/immunology
KW - Strongyloidiasis/immunology
KW - Tumor Necrosis Factor-alpha/immunology
KW - Animals
KW - Mice
KW - Mice, Inbred BALB C
KW - Rats
KW - Rats, Wistar
KW - Interferon-gamma/immunology
KW - Immunization
KW - Strongyloides ratti/immunology
KW - Sigmodontinae
KW - CD8-Positive T-Lymphocytes/immunology
KW - Antigens, Protozoan/immunology/pharmacology
KW - Filariasis/immunology
KW - Filarioidea/immunology
KW - Malaria/immunology
KW - Plasmodium berghei/immunology
KW - Protozoan Proteins/immunology/pharmacology
KW - Salmonella/immunology
KW - Strongyloidiasis/immunology
KW - Tumor Necrosis Factor-alpha/immunology
M3 - SCORING: Journal article
VL - 42
SP - 890
EP - 900
JO - EUR J IMMUNOL
JF - EUR J IMMUNOL
SN - 0014-2980
IS - 4
M1 - 4
ER -
