Human Cytomegalovirus mRNA-1647 Vaccine Candidate Elicits Potent and Broad Neutralization and Higher Antibody-Dependent Cellular Cytotoxicity Responses Than the gB/MF59 Vaccine

J Infect Dis. 2024 Aug 16;230(2):455-466. doi: 10.1093/infdis/jiad593.

Abstract

Background: MF59-adjuvanted gB subunit (gB/MF59) vaccine demonstrated approximately 50% efficacy against human cytomegalovirus (HCMV) acquisition in multiple clinical trials, suggesting that efforts to improve this vaccine design might yield a vaccine suitable for licensure.

Methods: A messenger RNA (mRNA)-based vaccine candidate encoding HCMV gB and pentameric complex (PC), mRNA-1647, is currently in late-stage efficacy trials. However, its immunogenicity has not been compared to the partially effective gB/MF59 vaccine. We assessed neutralizing and Fc-mediated immunoglobulin G (IgG) effector antibody responses induced by mRNA-1647 in both HCMV-seropositive and -seronegative vaccinees from a first-in-human clinical trial through 1 year following third vaccination using a systems serology approach. Furthermore, we compared peak anti-gB antibody responses in seronegative mRNA-1647 vaccinees to that of seronegative gB/MF59 vaccine recipients.

Results: mRNA-1647 vaccination elicited and boosted HCMV-specific IgG responses in seronegative and seropositive vaccinees, respectively, including neutralizing and Fc-mediated effector antibody responses. gB-specific IgG responses were lower than PC-specific IgG responses. gB-specific IgG and antibody-dependent cellular phagocytosis responses were lower than those elicited by gB/MF59. However, mRNA-1647 elicited higher neutralization and antibody-dependent cellular cytotoxicity (ADCC) responses.

Conclusions: Overall, mRNA-1647 vaccination induced polyfunctional and durable HCMV-specific antibody responses, with lower gB-specific IgG responses but higher neutralization and ADCC responses compared to the gB/MF59 vaccine.

Clinical trials registration: NCT03382405 (mRNA-1647) and NCT00133497 (gB/MF59).

Keywords: durability; gB/MF59 vaccine; human cytomegalovirus; mRNA-1647 vaccine; pentametric complex.

MeSH terms

  • Adjuvants, Immunologic* / administration & dosage
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Antibody-Dependent Cell Cytotoxicity
  • Cytomegalovirus Infections* / immunology
  • Cytomegalovirus Infections* / prevention & control
  • Cytomegalovirus Infections* / virology
  • Cytomegalovirus Vaccines* / administration & dosage
  • Cytomegalovirus Vaccines* / immunology
  • Cytomegalovirus* / genetics
  • Cytomegalovirus* / immunology
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Polysorbates* / administration & dosage
  • RNA, Messenger / genetics
  • RNA, Messenger / immunology
  • Squalene* / administration & dosage
  • Squalene* / immunology
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology
  • mRNA Vaccines* / administration & dosage
  • mRNA Vaccines* / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Cytomegalovirus Vaccines
  • glycoprotein B, Simplexvirus
  • Immunoglobulin G
  • MF59 oil emulsion
  • mRNA Vaccines
  • mRNA-1647 cytomegalovirus vaccine
  • Polysorbates
  • RNA, Messenger
  • Squalene
  • Viral Envelope Proteins

Associated data

  • ClinicalTrials.gov/NCT03382405
  • ClinicalTrials.gov/NCT00133497