Multi-antigenic human cytomegalovirus mRNA vaccines that elicit potent humoral and cell-mediated immunity
Open accessAbstract
A cytomegalovirus (CMV) vaccine that is effective at preventing congenital infection and reducing CMV disease in transplant patients remains a high priority as no approved vaccines exist. While the precise correlates of protection are unknown, neutralizing antibodies and antigen-specific T cells have been implicated in controlling infection. We demonstrate that the immunization of mice and nonhuman primates (NHPs) with lipid nanoparticles (LNP) encapsulating modified mRNA encoding CMV glycoproteins gB and pentameric complex (PC) elicit potent and durable neutralizing antibody titers. Since the protective correlates in pregnant women and transplant recipients may differ, we developed an additional mRNA vaccine expressing the immunodominant CMV T cell antigen pp65. Administration of pp65 vaccine with PC and gB elicited robust multi-antigenic T cell responses in mice. Our data demonstrate that mRNA/LNP is a versatile platform that enables the development of vaccination strategies that could prevent CMV infection and consequent disease in different target populations.
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Multivalent influenza and cytomegalovirus mRNA vaccines have shown that integration of multiple antigens can lead to robust nAb responses in pre-clinical models which correlate with protection for multiple vaccines.
“Multivalent influenza21 and cytomegalovirus22 mRNA vaccines have shown that integration of multiple antigens can lead to robust nAb responses in pre-clinical models which correlate with protection for multiple vaccines18,23.”
From Efficacy of an unmodified bivalent mRNA vaccine against SARS-CoV-2 variants in female small animal models (2023) · cites this paper as [22]
mRNA vaccines can combine different antigen mRNAs; for example, six separate mRNAs have been incorporated in a cytomegalovirus vaccine, five of which encode a single pentameric antigen and one encodes a glycoprotein antigen.
“Second, mRNA vaccines can combine different antigen mRNAs; for example, six separate mRNAs have been incorporated in a cytomegalovirus vaccine, five of which encode a single pentameric antigen and one encodes a glycoprotein antigen185.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [185]
A multiple-antigenic mRNA vaccine encoding the five CMV pentameric complex subunits together with CMV glycoprotein gB induced potent and durable neutralizing antibody titers in immunized mice and non-human primates.
“Together with an mRNA sequence against the CMV glycoprotein gB, this multiple-antigenic mRNA vaccine induced potent and durable neutralizing antibody titers in immunized mice and non-human primates [24].”
From Three decades of messenger RNA vaccine development (2019) · cites this paper as [24]
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- Authors
- John, S., Yuzhakov, O., Woods, A., Deterling, J., Hassett, K., Shaw, C. A., & Ciaramella, G.
- Affiliations
- Moderna Therapeutics (United States) (US)
- Corresponding author
- Ciaramella, Giuseppe
- Venue
- Vaccine
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 36
- Issue
- 12
- Pages
- 1689-1699
- ISSN
- 0264-410X (ISSN-L)
- OpenAlex
- W2789915301
- Cited by
- 229
- References
- 54
- Citations by year
- 2026: 10 · 2025: 30 · 2024: 33 · 2023: 32 · 2022: 42 · 2021: 34 · 2020: 27 · 2019: 15 · 2018: 6
- FWCI
- 15.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Vaccine (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Moderna
- Topics
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Keywords
- cytomegalovirus vaccine, mRNA vaccines, lipid nanoparticles, pentameric complex, pp65, T cell immunity, neutralizing antibodies, congenital cytomegalovirus infection, transplant recipients, non-human primates, immunogenicity
- MeSH terms
- Animals, Antibodies, Viral, Cell Line, Cytomegalovirus Infections, Cytomegalovirus, Female, Humans, Immunity, Cellular, Neutralization Tests, T-Lymphocytes, Vaccination, Vaccines, Synthetic, Gene Expression, Cytokines, Cytomegalovirus Vaccines, Mice, Immunity, Humoral, Antibodies, Neutralizing
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