Immunogenicity and protective activity of mRNA vaccine candidates against yellow fever virus in animal models

Medina-Magües, Lex G.; Mühe, Janine; Jasny, Edith; Medina-Magües, Emily S.; Roth, Nicole; Lopera-Madrid, Jaime; Salas-Quinchucua, Cristhian; Knuese, Cole; Petsch, Benjamin; Osorio, Jorge E.

doi:10.1038/s41541-023-00629-7

Cited by 3 publications

(4 citation statements)

References 47 publications

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“…Furthermore, IL-1 and IL-1ra are key regulators of the in ammatory response to RNA vaccines which are different in human and rodent cells 83 . Nevertheless, demonstration of high immunogenicity and protective e cacy of non-modi ed mRNA vaccines in non-human primates 44,45 , and tolerability in human trials 43 , indicates the high potential of this vaccine platform.…”

Section: Discussionmentioning

confidence: 99%

“…While the non-modi ed mRNA COVID-19 HERALD vaccine platform was discontinued by CureVac, it met the prespeci ed success criteria for e cacy against COVID-19 despite the low 12 µg mRNA dose 43 , which is lesser than that of BNT162b2 (30 µg) and Moderna (100 µg) COVID-19 vaccines. Therefore, the unmodi ed mRNA vaccine platform is also actively pursued 44,45 . Successful use of some PRR agonists as adjuvants for proteinbased vaccines (reviewed in ref.…”

Section: Introductionmentioning

confidence: 99%

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Andes virus mRNA vaccines: comparison of unmodified and modified mRNA platforms

Bukreyev

Kuzmin

Acosta

et al. 2023

Preprint

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Andes virus (ANDV) is a rodent-borne zoonotic orthohantavirus endemic in South America that causes hantavirus pulmonary syndrome in humans, with up to a 40% case fatality rate. We developed ANDV mRNA vaccines based on the M segment of the viral genome that codes for glycoproteins Gn and Gc in a single open reading frame of glycoprotein precursor (GPC). We generated RNAs either with regular uridine (U-mRNA) or N1-methylpseudouridine (m1Ψ-mRNA). Mice immunized by either ANDV U-mRNA or m1Ψ-mRNA developed similar germinal center responses in lymph nodes. Single cell RNA and BCR sequencing of germinal center B cells from vaccinated mice demonstrated similar levels of activation, except an additional cluster of cells exhibiting strong interferon response that was present in animals vaccinated with U-mRNA but not m1Ψ-mRNA. Furthermore, similar immunoglobulin class-switching and somatic hypermutations were observed for the two vaccines. Golden Syrian hamsters were immunized intramuscularly with 2 doses of the vaccines on days 0 and 21. The titers of Gn/Gc-binding antibodies were moderately greater for U-mRNA construct than for m1Ψ-mRNA construct, however, the titers of ANDV-neutralizing antibodies were equivalent. Vaccinated animals were challenged with a lethal dose of ANDV at 21 days after the boost, along with the naïve control group. All control animals succumbed to infection whereas all vaccinated animals survived without any detectable disease or viral load. The data demonstrate the development of effective vaccines against ANDV and the lack of a significant effect of m1Ψ mRNA modification on immunogenicity and protection in the hamster model.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Andes virus mRNA vaccines: comparison of unmodified and modified mRNA platforms

Bukreyev

Kuzmin

Acosta

et al. 2023

Preprint

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“…Macaques immunized with mRNA vaccines sustained high humoral and cellular immune responses for at least five months after the second vaccination dose. Overall, mRNA vaccines have shown promising immunogenicity and protection against flaviviruses, making them potential candidates for combating these infectious diseases [ 75 ].…”

Section: Rna Vaccines For Infectious Diseasesmentioning

confidence: 99%

Vaccines’ New Era-RNA Vaccine

Zhou,

Jiang,

Liao

et al. 2023

Viruses

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RNA vaccines, including conventional messenger RNA (mRNA) vaccines, circular RNA (circRNA) vaccines, and self-amplifying RNA (saRNA) vaccines, have ushered in a promising future and revolutionized vaccine development. The success of mRNA vaccines in combating the COVID-19 pandemic caused by the SARS-CoV-2 virus that emerged in 2019 has highlighted the potential of RNA vaccines. These vaccines possess several advantages, such as high efficacy, adaptability, simplicity in antigen design, and the ability to induce both humoral and cellular immunity. They also offer rapid and cost-effective manufacturing, flexibility to target emerging or mutant pathogens and a potential approach for clearing immunotolerant microbes by targeting bacterial or parasitic survival mechanisms. The self-adjuvant effect of mRNA-lipid nanoparticle (LNP) formulations or circular RNA further enhances the potential of RNA vaccines. However, some challenges need to be addressed. These include the technology’s immaturity, high research expenses, limited duration of antibody response, mRNA instability, low efficiency of circRNA cyclization, and the production of double-stranded RNA as a side product. These factors hinder the widespread adoption and utilization of RNA vaccines, particularly in developing countries. This review provides a comprehensive overview of mRNA, circRNA, and saRNA vaccines for infectious diseases while also discussing their development, current applications, and challenges.

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“…mRNA vaccine represents a significant advancement in nucleic acid vaccine technology 19 . With the clinical application of mRNA vaccines in the prevention of COVID-19, mRNA vaccine has demonstrated significant potential in combating various virulent pathogens [20][21][22][23] . Yet, the efficacy and suitability of mRNA vaccine in addressing HTNV is still an area of uncertainty.…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive Investigation of Glycoprotein-based Nucleic Acid Vaccines for Hantaan Virus

yang,

zhang,

Zhang

et al. 2024

Preprint

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Hemorrhagic fever with renal syndrome (HFRS) occurs throughout Eurasia with considerable morbidity and mortality. Currently, the absence of specific treatments or effective antiviral drugs for hantavirus infection makes developing safe and effective vaccines a high priority. Here, we report the development of three novel nucleic acid vaccine candidates, mRNA, DNA, and DNA encapsulated in lipid nanoparticles, encoding the glycoproteins of the Hantaan virus (HTNV). To comprehensively evaluate the potential of candidate HTNV nucleic acid vaccines in preventing HFRS, we focus on evaluating their immunogenicity and efficacy in mice and comparing them with an inactivated vaccine as the benchmark. Our findings reveal that all candidate vaccines activated instant and sustained immune responses, offering effective in vivo protection. Notably, the nucleic acid vaccines demonstrated distinct advantages over the inactivated vaccine, in both humoral and cellular immunity. These results mark a significant step in developing nucleic acid vaccines for HTNV, suggesting that sequential immunization with DNA and mRNA vaccines could further amplify the advantages of nucleic acid vaccines.

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Immunogenicity and protective activity of mRNA vaccine candidates against yellow fever virus in animal models

Cited by 3 publications

References 47 publications

Andes virus mRNA vaccines: comparison of unmodified and modified mRNA platforms

Andes virus mRNA vaccines: comparison of unmodified and modified mRNA platforms

Vaccines’ New Era-RNA Vaccine

A Comprehensive Investigation of Glycoprotein-based Nucleic Acid Vaccines for Hantaan Virus

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