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A5.11 Vaccination against TNF and side effects in listeria infection model
  1. N Belmellat1,2,
  2. L Faunonnier3,
  3. B Ryffel3,
  4. MC Boissier1,2,4,
  5. E Assier1,2
  1. 1Inserm UMR 1125, Bobigny France
  2. 2Sorbonne Paris Cité Université Paris 13, Bobigny France
  3. 3CNRS UMR7355, INEM, Orléans, France
  4. 4Assistance Publique – Hôpitaux de Paris (AP-HP) Groupe Hospitalier Avicenne - Jean Verdier – René Muret, Service de Rhumatologie, Bobigny France

Abstract

Background Anti-TNF therapy has been a successful treatment strategy for rheumatoid arthritis disease, but is associated with reduced resistance to infection. Recently, active anti-TNF immunotherapy has shown its promising efficiency in a pilot phase IIA clinical trial. In mice, TNF is essential to control Listeria monocytogenes. We aimed at better defining the infectious risk/benefit ratio of TNF-a neutralisation of active immunotherapy strategy. For this purpose, we developed a vaccine (mTNF-K) targeting murine TNF-a by coupling the cytokine to the carrier protein keyhole limpet hemocyanin (KLH). We reported mTNF-K attenuated collagen-induced arthritis (CIA) to same extent as etanercept.

Objectives Here we evaluated the safety of TNF-a blockade induced by the vaccine in Listeria infection model.

Materials and methods 4 groups of 10 C57Bl/6 mice were used and compared with a murine TNF KO group (same background). Wild type mice were treated either by mTNF-K, etanercept, KLH or PBS. Vaccines were emulsified in CFA (day 0) or IFA (days 13, 27 and 40) before injections. All groups were infected at day 44 by 104 cfu of Listeria monocytogenes (LO28 strain). Mice groups were divided in two arms: one was euthanized 4 days post-infection, and the bacterial burden was evaluated in the spleen and the liver; survival of the lasting mice was evaluated until day 11. Blood sampling was conducted at day 34 and 47 in order to evaluate anti-TNF-a antibody production.

Results A sustained anti-TNF-a antibody production was obtained in mTNF-K vaccinated mice. At day 4 post-infection, mTNF-K and non-targeted-TNF-a treatments groups (KLH, PBS) presented lower bacterial burden in liver and spleen than TNF KO and etanercept groups. At day 11, all mice of PBS and mTNF-K groups survived to infection. Large lesions in livers were observed only within TNF KO and etanercept groups.

Conclusions Active immunotherapy with mTNF-K vaccine seems to preserve adequate host immunity against Listeria infection in this model.

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