ENHANCEMENT OF THE ANTIBODY-RESPONSE TO FLAVIVIRUS B-CELL EPITOPES BY USING HOMOLOGOUS OR HETEROLOGOUS T-CELL EPITOPES

We have been investigating the T-helper (T(h))-cell response to the flavivirus envelope (E) glycoprotein. In our studies with Murray Valley encephalitis (MVE) virus, we previously identified synthetic peptides capable of priming T(h) lymphocytes for an in vitro antivirus proliferative response (J. H. Mathews, J. E. Allan, J. T. Roehrig, J. R. Brubaker, and A. R. Hunt, J. Virol. 65:5141-5148, 1991). We have now characterized in vivo T(h)-cell priming activity of one of these peptides (MVE 17, amino acids 356 to 376) and an analogous peptide derived from the E-glycoprotein sequence of the dengue (DEN) 2, Jamaica strain (DEN 17, amino acids 352 to 368). This DEN peptide also primed the T(h)-cell compartment in BALB/c mice, as measured by in vitro proliferation and interleukin production. The failure of some MVE and DEN virus synthetic peptides to elicit an antibody response in BALB/c mice could be overcome if a T(h)-cell epitope-containing peptide was included in the immunization mixture. A more detailed analysis of the structural interactions between T(h)-cell and B-cell epitope donor peptides revealed that the peptides must be linked to observe the enhanced antibody response. Blockage or deletion of the free cysteine residue on either peptide abrogated the antibody response. The most efficient T-B-cell epitope interaction occurred when the peptides were colinearly synthesized. These T(h)-Cell-stimulating peptides were also functional with the heterologous B-cell epitope-containing peptides. The T(h)-cell epitope on DEN 17 was more potent than the T(h)-cell epitope on MVE 17.