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Vaccination against filarial infection - use of loa loa and a murine model for identification of protective mechanisms and antigens

Objective

* To determine the mechanisms of protection induced by irradiated infective larvae of Loa loa in monkey and of Litomosoides sigmodontis in laboratory mice.
* To identify the mechanisms of natural protection against microfilariae of
L. sigmodontis in laboratory mice and cotton rats.
* To identify and clone antigens associated with protection, for incorporation, into live single dose oral recombinant vaccines.
Expected Outcome

1) Determination of the relative role of Th1 versus Th2 responses in the development of protective immunity following immunisation of mice with irradiated infective larvae of L. sigmodontis.
2) Comparison with the Loa loa specific immune responses in mandrills following a similar procedure of immunisation with irradiated larvae.
3) Comparison with natural protection against microfilariae of L. sigmodontis in mice and cotton rats.
4) Identification and production of at least some antigens associated with protection.
* Spleen T-cell and antibody responses will be measured in L. simodontis vaccinated mice and controls, in the presence of antigens derived from microfilariae, L3 and adult worms. Knock-out mice and cytokine depletion with specific monoclonal antibodies will be used. The pattern of antigen recognition will be investigated by Western blot and radio-immuno-precipitation.

* A similar investigation will be performed with Loa loa mandrills.

* Survival and migration of Loa loa L3 in vaccinated and control mice, and the associated pathology will be studied.

* The pattern of microfilaraemia and the immune response of mice and cotton rats infected with normal L. sigmodontis L3 will be investigated, as in 1. Modulatory effects of cytokines will also be investigated.

* mRNA from L. sigmodontis and Loa loa infective larvae will be isolated for production of cDNA libraries. cDNA clones identified in the primary screens will be sub-cloned in high expression vectors for production of the corresponding recombinant antigens.

* Screening reagents (rabbit antisera) from L. loa and L. sigmodontis stages (adult worms, microfilariae, infective larvae, fourth stage larvae) will be prepared. Antisera raised against fractionated native and recombinant antigens will be used to localise the molecules in the parasites.


Contract number ERBIC18CT950026

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

MUSEUM NATIONAL D'HISTOIRE NATURELLE
Address
Rue Buffon 61
75231 Paris
France

Participants (4)

Centre International de Recherches Medicales de Franceville
Gabon
Address

10 Franceville
THE UNIVERSITY OF TUEBINGEN
Germany
Address
27,Wilhelmstrasse 27
72074 Tuebingen
UNIVERSITY OF BUEA
Cameroon
Address

20 Buea
UNIVERSITY OF EDINBURGH
United Kingdom
Address
Easter Bush Sir Alexander Robertson Building
EH25 9RG Roslin