Human cytomegalovirus gH/gL/UL128/UL130/UL131A complex elicits potently neutralizing antibodies in mice.
Human cytomegalovirus (HCMV) is a member of the β-herpesvirus family that causes significant disease worldwide. Although evidence exists that neutralizing antibodies and cytotoxic T cell responses to HCMV antigens can prevent HCMV disease and/or infection, there are no approved vaccines to prevent HCMV disease. Over the past 10 years, multiple HCMV vaccines have been tested in man but only partial protection has been achieved in these studies. HCMV contains multiple surface-expressed glycoproteins that are critical to viral entry, including gB, the gM/gN complex, the gH/gL complex, and a pentameric gH/gL/UL128/UL130/UL131A complex. Recently we showed that viral replicon particles (VRPs) expressing the gH/gL complex elicited more potently neutralizing antibodies than VRPs expressing gB in mice. Here we compare the immunogenicity of VRPs encoding the HCMV gH/gL and pentameric complexes, as well as purified gH/gL and pentameric complexes administered in the presence or absence of the MF59 adjuvant. The results of these studies indicate that the pentameric complex elicits significantly higher levels of neutralizing antibodies than the gH/gL complex, and that MF59 significantly increases the potency of each complex. In addition, we show that animals immunized with pentamer encoding VRPs or the pentameric subunit produce antibodies that recognize a broad range of antigenic sites on the complex. Taken together, these studies support the utility of the pentameric complex in HCMV vaccine candidates.
Novartis Vaccines: 45 Sidney Street, Cambridge, MA 02139, United States.
Yingxia
Y
Wen
Novartis Vaccines: 45 Sidney Street, Cambridge, MA 02139, United States.
James
J
Monroe
Novartis Vaccines: 45 Sidney Street, Cambridge, MA 02139, United States.
Christine
C
Linton
Novartis Vaccines: 45 Sidney Street, Cambridge, MA 02139, United States.
Jacob
J
Archer
Novartis Vaccines: 45 Sidney Street, Cambridge, MA 02139, United States.
Clayton W
CW
Beard
Novartis Vaccines: 45 Sidney Street, Cambridge, MA 02139, United States.
Susan W
SW
Barnett
Novartis Vaccines: 45 Sidney Street, Cambridge, MA 02139, United States.
Giuseppe
G
Palladino
Novartis Vaccines: 45 Sidney Street, Cambridge, MA 02139, United States. Electronic address: peter.mason@novartis.com.
Peter W
PW
Mason
Novartis Vaccines: 45 Sidney Street, Cambridge, MA 02139, United States. Electronic address: andrea.carfi@novartis.com.
Andrea
A
Carfi
Novartis Vaccines: 45 Sidney Street, Cambridge, MA 02139, United States.
Anders E
AE
Lilja
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood*; D000918:Antibody Specificity; D003587:Cytomegalovirus; D022482:Cytomegalovirus Vaccines / Q000276:immunology*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology*; D008807:Mice, Inbred BALB C; D046912:Multiprotein Complexes / Q000276:immunology; D011136:Polysorbates / Q000494:pharmacology; D012093:Replicon; D013185:Squalene / Q000494:pharmacology; D058425:Vaccines, Virus-Like Particle / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D022482:Cytomegalovirus Vaccines; C089950:MF59 oil emulsion; D008562:Membrane Glycoproteins; D046912:Multiprotein Complexes; D011136:Polysorbates; C532797:UL128 protein, human cytomegalovirus; C502890:UL130 protein, human cytomegalovirus; D058425:Vaccines, Virus-Like Particle; D014759:Viral Envelope Proteins; C499358:glycoprotein H, Human cytomegalovirus; D013185:Squalene
Cytomegalovirus; Neutralizing antibodies; Pentameric complex; Vaccine