title: Preclinical evaluations of peptide-conjugate vaccines targeting the antigenic domain-2 of glycoprotein B of human cytomegalovirus.
abstract: The Antigenic Domain 2 (AD-2) is a short region near the N-terminus of glycoprotein B of human cytomegalovirus (HCMV). AD-2 has been shown to contain linear epitopes that are targets for neutralizing monoclonal antibodies from human subjects with natural HCMV infection. However, AD-2 appears to be masked by the adjacent immunodominant AD-1 region. We assessed a serum panel from HCMV-seropositive individuals and found a wide range of antibody titers to AD-2; these did not correlate to serum neutralization. To expose potential epitopes in AD-2, we constructed a series of AD-2 peptide-conjugate vaccines. Mice were immunized 3 times and produced high and sustained antibody titers to AD-2 peptides, but neutralization was weak even after a single boost with whole HCMV virions. Rabbits were likewise immunized with AD-2 peptide vaccines, and produced a robust antibody response, but neutralization was inferior to a recombinant gB vaccine with an oil-in-water adjuvant. These results highlight the challenges of developing a peptide-based vaccine specific to the HCMV gB AD-2 region.
authors.affiliation: a Merck Research Laboratories, Merck and Companies, Incorporated , Kenilworth , NJ , USA.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Finnefrock
authors.affiliation: a Merck Research Laboratories, Merck and Companies, Incorporated , Kenilworth , NJ , USA.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Freed
authors.affiliation: a Merck Research Laboratories, Merck and Companies, Incorporated , Kenilworth , NJ , USA.
authors.forename: Aimin
authors.initials: A
authors.lastname: Tang
authors.affiliation: a Merck Research Laboratories, Merck and Companies, Incorporated , Kenilworth , NJ , USA.
authors.forename: Fengsheng
authors.initials: F
authors.lastname: Li
authors.affiliation: a Merck Research Laboratories, Merck and Companies, Incorporated , Kenilworth , NJ , USA.
authors.forename: Xi
authors.initials: X
authors.lastname: He
authors.affiliation: a Merck Research Laboratories, Merck and Companies, Incorporated , Kenilworth , NJ , USA.
authors.forename: Chengwei
authors.initials: C
authors.lastname: Wu
authors.affiliation: a Merck Research Laboratories, Merck and Companies, Incorporated , Kenilworth , NJ , USA.
authors.forename: Debbie
authors.initials: D
authors.lastname: Nahas
authors.affiliation: a Merck Research Laboratories, Merck and Companies, Incorporated , Kenilworth , NJ , USA.
authors.forename: Dai
authors.initials: D
authors.lastname: Wang
authors.affiliation: a Merck Research Laboratories, Merck and Companies, Incorporated , Kenilworth , NJ , USA.
authors.forename: Tong-Ming
authors.initials: TM
authors.lastname: Fu
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D022482:Cytomegalovirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D004353:Drug Evaluation, Preclinical; D005260:Female; D008807:Mice, Inbred BALB C; D011817:Rabbits; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D022482:Cytomegalovirus Vaccines; D018074:Vaccines, Conjugate; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus
keywords: Cytomegalovirus (CMV); in vivo; neutralizing antibodies; peptides; vaccine