DEVELOPMENT OF A CYTOMEGALOVIRUS SUBUNIT VACCINE

CHIRON CORPORATION IS DEVELOPING A SUBUNIT VACCINE DIRECTED AGAINST HUMAN CYTOMEGALOVIRUS (CMV), USING RECOMBINANT DERIVATIVES OF VIRAL GLYCOPROTEINS THAT ARE CAPABLE OF INDUCING NEUTRALIZING ANTIBODIES IN HUMANS. A CANDIDATE ANTIGEN FOR THIS VACCINE IS CMV GLYCOPROTEIN H (GH), WHICH HAS BEEN SHOWN TO INDUCE A STRONG COMPLEMENT-INDEPENDENT NEUTRALIZING RESPONSE IN ANIMALS. RECOMBINANT DERIVATIVES OF GH WILL BE ISOLATED THAT ARE EFFICIENTLY EXPRESSED AND SECRETED FROM MAMMALIAN CELLS AND THAT RETAIN THE GH NEUTRALIZING EPITOPES. USING IN VITRO MUTAGENESIS AND OTHER RECOMBINANT DNA TECHNIQUES, DELETED FORMS OF GH WILL BE GENERATED THAT WILL BE TESTED IN MAMMALIAN CELLS. IN PHASE II, EXPRESSION PLASMIDS ENCODING GH CONSTRUCTS THAT DIRECT SYNTHESIS OF HIGH LEVELS OF IMMUNOLOGICALLY REACTIVE GH WILL BE USED TO DEVELOP STABLE GH-PRODUCING CELL LINES. THIS GH WILL BE PURIFIED AND TESTED FOR IMMUNOGENICITY IN ANIMALS AND, ULTIMATELY, HUMANS. THOSE GHANTIGENS THAT ELICIT A STRONG NEUTRALIZING RESPONSE WILL BE USED FOR THE DEVELOPMENT OF A VACCINE CAPABLE OF REDUCING THE SERIOUS CONSEQUENCES OF CMV DISEASE IN NEONATES AND TRANSPLANT RECIPIENTS.