CYTOTOXIC T-LYMPHOCYTE RESPONSES TO MEASLES IN W AFRICA

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The broad long term aim of this Project is to gain knowledge of immunity to measles effected by cytotoxic T lymphocytes (CTL) in West Africans infected with, or vaccinated against, measles. The specific aims of the project are: (1) to test whether direct killing by CD8 + CTL occurs in the acute phase of measles and to determine to which of 3 measles antigens, the hemagglutinin (HA), the fusion (F) or the nucleoprotein (NP), this type of immunity is directed. To achieve this aim recombinant vaccinia/measles viruses expressing these proteins will be used to infect B cell targets matched by HLA class l locus of the donor and tested in cytotoxicity assays. (2) to test whether recombinant attenuated vaccinia/measles viruses and canary pox/measles recombinants, which are candidates for future measles vaccines, can be used to recall CTL in children who have recently been infected with measles and in children vaccinated against measles. To achieve this aim, these non-replicating virus vectors will be used to infect autologous mononuclear cells in order to stimulate CTL to kill autologous B cell targets infected with measles virus. Use of anti CD4 and anti CD8 antibody will define which type of cell effects killing. (3) to test, using methods described in 1 and 2, whether exposure to natural measles boosts CTL responses in mothers immune to measles and in siblings vaccinated against measles. (4) to identify the peptide epitopes contained in the HA, F and NP antigens of the Edmonston and local strains of measles virus, which are recognized by HLA class 1 restricted CTL common to West Africans. The amino acid sequences of the 3 measles antigens will be examined to predict which will bind to the common West African HLA class 1 motifs and will then be tested in assembly assays using T2 mutant cells transfected with these HLA genes. Those that bind with high affinity will be tested in cytotoxicity assays. Knowledge gained from the above studies will allow decisions as to whether the attenuated measles recombinant viruses are likely to be useful vaccines in West Africa.