Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article 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).
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11326847 | PMC |
| http://dx.doi.org/10.1093/infdis/jiad593 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Developing a Vaccine Against Human Cytomegalovirus: Identifying and Targeting HCMV's Immunological Achilles' Heel.
Vaccines (Basel)
April 2025
Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London NW3 2PP, UK.
Human cytomegalovirus (HCMV) is a critical pathogen in immunocompromised populations, such as organ transplant recipients as well as congenitally infected neonates with immature immune systems. Despite decades of research and the growing financial burden associated with the management of HCMV, there is no licensed vaccine to date. In this review, we aim to outline the complexity of HCMV and the antigens it presents and the journey and challenges of developing an effective HCMV vaccine, as well as further highlight the recent analyses of the most successful vaccine candidate so far-gB/MF59.
View Article and Find Full Text PDFMultivalent cytomegalovirus glycoprotein B nucleoside modified mRNA vaccines did not demonstrate a greater antibody breadth.
NPJ Vaccines
February 2024
Department of Pediatrics, Weill Cornell Medicine, New York, NY, 10065, USA.
Human cytomegalovirus (HCMV) remains the most common congenital infection and infectious complication in immunocompromised patients. The most successful HCMV vaccine to date, an HCMV glycoprotein B (gB) subunit vaccine adjuvanted with MF59, achieved 50% efficacy against primary HCMV infection. A previous study demonstrated that gB/MF59 vaccinees were less frequently infected with HCMV gB genotype strains most similar to the vaccine strain than strains encoding genetically distinct gB genotypes, suggesting strain-specific immunity accounted for the limited efficacy.
View Article and Find Full Text PDFHuman 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
August 2024
Department of Pediatrics, Weill Cornell Medicine, New York, New York.
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.
Characterization of epitopes of human monoclonal antibodies against cytomegalovirus glycoprotein B for neutralization and antibody-dependent phagocytosis.
Vaccine
July 2023
Kikuchi Research Center, KM Biologics Co., Ltd, Japan. Electronic address:
Article Synopsis
- Congenital cytomegalovirus (CMV) infections are a major cause of hearing loss and neurological issues in children, making the development of vaccines a top public health priority.
- The existing gB/MF59 vaccine shows only about 50% efficacy against natural infections, primarily generating high antibody levels that don't effectively neutralize the virus.
- Recent findings indicate non-neutralizing antibody functions, particularly antibody-dependent phagocytosis, are crucial for vaccine design, with key insights suggesting that focusing on specific epitopes on domains I and II of the gB protein could enhance vaccine development efforts.
A temperature-dependent virus-binding assay reveals the presence of neutralizing antibodies in human cytomegalovirus gB vaccine recipients' sera.
J Gen Virol
June 2023
Institute of Immunity and Transplantation, Division of Infection and Immunity, UCL, Royal Free Campus, London, NW3 2PP, UK.
Human cytomegalovirus (HCMV) remains an important cause of mortality in immune-compromised transplant patients and following congenital infection. Such is the burden, an effective vaccine strategy is considered to be of the highest priority. The most successful vaccines to date have focused on generating immune responses against glycoprotein B (gB) - a protein essential for HCMV fusion and entry.
View Article and Find Full Text PDF