Protection against lethal cytomegalovirus infection by a recombinant vaccine containing a single nonameric T-cell epitope

The regulatory immediate-early (IE) protein pp89 of murine
cytomegalovirus induces CD8+ T lymphocytes that protect against
lethal murine cytomegalovirus infection. The IE1 epitope is the
only epitope of pp89 that is recognized by BALB/c cytolytic T
lymphocytes (CTL). Using synthetic peptides, the optimal and
minimal antigenic sequences of the IE1 epitope have been defined.
To evaluate the predictive value of data obtained with synthetic
peptides, recombinant vaccines encoding this single T-cell epitope
were constructed using as a vector the hepatitis B virus core
antigen encoded in recombinant vaccinia virus. In infected cells
expressing the chimeric proteins, only IE1 epitope sequences that
were recognized as synthetic peptides at concentrations lower than
10(-6) M were presented to CTL. Vaccination of mice with the
recombinant vaccinia virus that encoded a chimeric protein carrying
the optimal 9-amino-acid IE1 epitope sequence elicited CD8+ T
lymphocytes with antiviral activity and, furthermore, protected
against lethal disease. The results thus show for the first time
that recombinant vaccines containing a single foreign nonameric CTL
epitope can induce T-lymphocyte-mediated protective immunity.