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

Publication ,  Journal Article
Hu, X; Karthigeyan, KP; Herbek, S; Valencia, SM; Jenks, JA; Webster, H; Miller, IG; Connors, M; Pollara, J; Andy, C; Gerber, LM; Walter, EB ...
Published in: J Infect Dis
August 16, 2024

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).

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Published In

J Infect Dis

DOI

EISSN

1537-6613

Publication Date

August 16, 2024

Volume

230

Issue

2

Start / End Page

455 / 466

Location

United States

Related Subject Headings

  • mRNA Vaccines
  • Viral Envelope Proteins
  • Squalene
  • RNA, Messenger
  • Polysorbates
  • Microbiology
  • Immunoglobulin G
  • Humans
  • Cytomegalovirus Vaccines
  • Cytomegalovirus Infections
 

Citation

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Hu, X., Karthigeyan, K. P., Herbek, S., Valencia, S. M., Jenks, J. A., Webster, H., … Permar, S. R. (2024). 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, 230(2), 455–466. https://doi.org/10.1093/infdis/jiad593
Hu, Xintao, Krithika P. Karthigeyan, Savannah Herbek, Sarah M. Valencia, Jennifer A. Jenks, Helen Webster, Itzayana G. Miller, et al. “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 230, no. 2 (August 16, 2024): 455–66. https://doi.org/10.1093/infdis/jiad593.
Hu X, Karthigeyan KP, Herbek S, Valencia SM, Jenks JA, Webster H, Miller IG, Connors M, Pollara J, Andy C, Gerber LM, Walter EB, Edwards KM, Bernstein DI, Hou J, Koch M, Panther L, Carfi A, Wu K, Permar SR. 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.
Journal cover image

Published In

J Infect Dis

DOI

EISSN

1537-6613

Publication Date

August 16, 2024

Volume

230

Issue

2

Start / End Page

455 / 466

Location

United States

Related Subject Headings

  • mRNA Vaccines
  • Viral Envelope Proteins
  • Squalene
  • RNA, Messenger
  • Polysorbates
  • Microbiology
  • Immunoglobulin G
  • Humans
  • Cytomegalovirus Vaccines
  • Cytomegalovirus Infections