Protection of mice against lethal viral infection by synthetic peptides corresponding to B- and T-cell recognition sites of influenza A hemagglutinin.

Previously, we reported 12 synthetic T- and B-cell recognition regions representing surface areas of the hemagglutinin (HA) of X31 influenza virus. In the present study, four of these peptides were examined in Balb/c mice for their ability to produce protective immunity against lethal infection with a dose equivalent to 10 LD50 of influenza virus. These peptides corresponded to the following sequences: 23-36 (HA1-1); 138-152 (HA1-3); 183-199 (HA1-6) and 1-11 (HA2-10). Each of the selected peptides, in their free form, evoked anti-peptide antibodies that cross-react with intact X31 virus. Two of the peptides, HA1-1 and HA1-3, also elicited virus-specific delayed type hypersensitivity (DTH) responses. These two peptides, when injected into mice, not only failed to protect the immunized mice against challenge with influenza virus, but in fact caused greater susceptibility to viral infection as compared to control animals that had been injected with saline. In contrast, peptides HA1-6 and HA2-10, which were unable to induce adequate virus-specific DTH responses, conferred 42-46% and 54-73% protection, respectively, compared to the control group that received only saline (P < 0.03 to P < 0.01).