title: Nematode-induced interference with the anti-Plasmodium CD8+ T-cell response can be overcome by optimizing antigen administration.
abstract: 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.
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Kolbaum
authors.forename: Susanne
authors.initials: S
authors.lastname: Tartz
authors.forename: Wiebke
authors.initials: W
authors.lastname: Hartmann
authors.forename: Susanne
authors.initials: S
authors.lastname: Helm
authors.forename: Andreas
authors.initials: A
authors.lastname: Nagel
authors.forename: Volker
authors.initials: V
authors.lastname: Heussler
authors.forename: Peter
authors.initials: P
authors.lastname: Sebo
authors.forename: Bernhard
authors.initials: B
authors.lastname: Fleischer
authors.forename: Thomas
authors.initials: T
authors.lastname: Jacobs
authors.forename: Minka
authors.initials: M
authors.lastname: Breloer
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005368:Filariasis / Q000276:immunology*; D005370:Filarioidea / Q000276:immunology*; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology; D008288:Malaria / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012475:Salmonella / Q000276:immunology; D016205:Sigmodontinae; D017170:Strongyloides ratti / Q000276:immunology*; D013322:Strongyloidiasis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D015800:Protozoan Proteins; D014409:Tumor Necrosis Factor-alpha; C041595:circumsporozoite protein, Protozoan; D007371:Interferon-gamma