Safety and immunogenicity of mRNA-LNP COVID-19 vaccine CVnCoV in Latin American adults: A phase 2 randomized study

Sáez-Llorens, Xavier; Lanata, Claudio F.; Aranguren, Elaine; Celis, Carlos R.; Cornejo, Rubelio; DeAntonio, Rodrigo; Ecker, Lucie; Garrido, Diegi; Gil, Ana I.; Gonzales, Marina; Hess‐Holtz, Morgan; Leroux‐Roels, Geert; Junker, Helga; Kays, Sarah-Katharina; Koch, Sven D.; Lazzaro, Sandra; Mann, Philipp; Quintini, Gianluca; Srivastava, Barkha; Vahrenhorst, Dominik; Eisenhart-Rothe, Philipp von; Wolz, Olaf‐Oliver; Oostvogels, Lidia

doi:10.1016/j.jvacx.2022.100189

Cited by 12 publications

(19 citation statements)

References 19 publications

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“…Nanocarriers is able to effectively prevent RNA degradation and increase its stability, 113 simultaneously package the immune adjuvant to increase the immunogenicity of the vaccine, increase the cross-presentation of antigen, and induce DC maturation and increase the CTL response. 114 Therefore, the use of LNP can shorten the time needed to produce a personalized vaccine, and extend the shelf life of the vaccine, which has a relatively broad development prospect. 115 As for the new technique of personalized antigens, 97 patient tumor individualized sequencing, analysis, identification, and screening are time-consuming process.…”

Section: Monocyte-derived Dendritic Cells (Modcs) Have Limited Functi...mentioning

confidence: 99%

“…Besides the common electroporation methods, 112 mRNA can also be loaded with lipid nanoparticles (LNP). Nanocarriers is able to effectively prevent RNA degradation and increase its stability, 113 simultaneously package the immune adjuvant to increase the immunogenicity of the vaccine, increase the cross‐presentation of antigen, and induce DC maturation and increase the CTL response 114 . Therefore, the use of LNP can shorten the time needed to produce a personalized vaccine, and extend the shelf life of the vaccine, which has a relatively broad development prospect 115 …”

Section: Existing Challenges and Future Approaches To DC Immunotherapymentioning

confidence: 99%

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Dendritic cell vaccines improve the glioma microenvironment: Influence, challenges, and future directions

Zhou

Jia

et al. 2022

Cancer Medicine

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Introduction Gliomas, especially the glioblastomas, are one of the most aggressive intracranial tumors with poor prognosis. This might be explained by the heterogeneity of tumor cells and the inhibitory immunological microenvironment. Dendritic cells (DCs), as the most potent in vivo functional antigen‐presenting cells, link innate immunity with adaptive immunity. However, their function is suppressed in gliomas. Therefore, overcoming the dysfunction of DCs in the TME might be critical to treat gliomas. Method In this paper we proposed the specificity of the glioma microenvironment, analyzed the pathways leading to the dysfunction of DCs in tumor microenvironment of patients with glioma, summarized influence of DC‐based immunotherapy on the tumor microenvironment and proposed new development directions and possible challenges of DC vaccines. Result DC vaccines can improve the immunosuppressive microenvironment of glioma patients. It will bring good treatment prospects to patients. We also proposed new development directions and possible challenges of DC vaccines, thus providing an integrated understanding of efficacy on DC vaccines for glioma treatment.

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Section: Monocyte-derived Dendritic Cells (Modcs) Have Limited Functi...mentioning

confidence: 99%

Section: Existing Challenges and Future Approaches To DC Immunotherapymentioning

confidence: 99%

Dendritic cell vaccines improve the glioma microenvironment: Influence, challenges, and future directions

Zhou

Jia

et al. 2022

Cancer Medicine

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“…Frontiers in Bioengineering and Biotechnology frontiersin.org encapsulated in LNP (Kremsner et al, 2021;Rauch et al, 2021;Sáez-Llorens et al, 2022) (Figure 3A), which was expected to be cheaper and more stable in refrigerated storage than those developed by Pfizer-BioNTech and Moderna. These last vaccines contain a pseudouridine mRNA nucleotide in place of the normal uridine nucleotide to circumvent immune inflammatory reactions (Karikó et al, 2005) that could be activated through detection of the foreign S viral mRNA (Morais et al, 2021) (Figure 3A).…”

Section: Covid-19 Vaccines By Nano-based Strategies: Prevention and T...mentioning

confidence: 99%

“…These last vaccines contain a pseudouridine mRNA nucleotide in place of the normal uridine nucleotide to circumvent immune inflammatory reactions (Karikó et al, 2005) that could be activated through detection of the foreign S viral mRNA (Morais et al, 2021) (Figure 3A). Although CureVac's vaccine bears normal uridine (Kremsner et al, 2021), it was developed altering the S viral mRNA genome code in a way that the protein is not affected (Kremsner et al, 2021), but helps to evade immune detection ( (Rauch et al, 2021;Sáez-Llorens et al, 2022); analyzed in (Dolgin, 2021)). The formulation of CurveVac's LNPs consists in cationic lipid (Acuitas Therapeutics), phospholipid, cholesterol and PEG-lipid conjugate (reviewed in (Kim et al, 2021a;Schoenmaker et al, 2021;Verbeke et al, 2021)) (Figure 3A).…”

Section: Covid-19 Vaccines By Nano-based Strategies: Prevention and T...mentioning

confidence: 99%

Nanomaterials to combat SARS-CoV-2: Strategies to prevent, diagnose and treat COVID-19

Valenzuela-Fernandez

Cabrera-Rodríguez

Ciuffreda

et al. 2022

Front. Bioeng. Biotechnol.

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the associated coronavirus disease 2019 (COVID-19), which severely affect the respiratory system and several organs and tissues, and may lead to death, have shown how science can respond when challenged by a global emergency, offering as a response a myriad of rapid technological developments. Development of vaccines at lightning speed is one of them. SARS-CoV-2 outbreaks have stressed healthcare systems, questioning patients care by using standard non-adapted therapies and diagnostic tools. In this scenario, nanotechnology has offered new tools, techniques and opportunities for prevention, for rapid, accurate and sensitive diagnosis and treatment of COVID-19. In this review, we focus on the nanotechnological applications and nano-based materials (i.e., personal protective equipment) to combat SARS-CoV-2 transmission, infection, organ damage and for the development of new tools for virosurveillance, diagnose and immune protection by mRNA and other nano-based vaccines. All the nano-based developed tools have allowed a historical, unprecedented, real time epidemiological surveillance and diagnosis of SARS-CoV-2 infection, at community and international levels. The nano-based technology has help to predict and detect how this Sarbecovirus is mutating and the severity of the associated COVID-19 disease, thereby assisting the administration and public health services to make decisions and measures for preparedness against the emerging variants of SARS-CoV-2 and severe or lethal COVID-19.

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“…A phase I dose-escalation study (CV-NCOV-001) using 2-20 µg of CVnCoV demonstrated an acceptable safety profile in adults aged 18-60 years, and two vaccine doses, administered 28 days apart, induced neutralizing antibodies, in addition to binding IgG antibodies against both the SARS-CoV-2 spike protein and its receptor binding domain (RBD) [6]. Thereafter, a randomized phase IIa study (CV-NCOV-002) was conducted in adults aged 18-60 years and >60 years of age with dose levels of 6 and 12 µg of CVnCoV [7]. This study confirmed that two doses of 12 µg were safe and induced a robust humoral response, including immune memory responses.…”

Section: Introductionmentioning

confidence: 99%

Innate Responses to the Former COVID-19 Vaccine Candidate CVnCoV and Their Relation to Reactogenicity and Adaptive Immunogenicity

Wolz,

Vahrenhorst,

Quintini

et al. 2024

Vaccines

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Vaccines are highly effective at preventing severe coronavirus disease (COVID-19). With mRNA vaccines, further research is needed to understand the association between immunogenicity and reactogenicity, which is defined as the physical manifestation of an inflammatory response to a vaccination. This study analyzed the immune response and reactogenicity in humans, post immunization, to the former SARS-CoV-2 mRNA investigational vaccine CVnCoV (CV-NCOV-001 and CV-NCOV-002 clinical trials). Immunogenicity was investigated using whole-blood RNA sequencing, serum cytokine levels, and SARS-CoV-2-specific antibodies. The T cell responses in peripheral blood were assessed using intracellular cytokine staining (ICS) and high-dimensional profiling in conjunction with SARS-CoV-2 antigen-specificity testing via mass cytometry. Reactogenicity was graded after participants’ first and second doses of CVnCoV using vaccine-related solicited adverse events (AEs). Finally, a Spearman correlation was performed between reactogenicity, humoral immunity, and serum cytokine levels to assess the relationship between reactogenicity and immunogenicity post CVnCoV vaccination. Our findings showed that the gene sets related to innate and inflammatory immune responses were upregulated one day post CVnCoV vaccination, while the gene sets related to adaptive immunity were upregulated predominantly one week after the second dose. The serum levels of IFNα, IFNγ, IP-10, CXCL11, IL-10, and MCP-1 increased transiently, peaking one day post vaccination. CD4+ T cells were induced in all vaccinated participants and low frequencies of CD8+ T cells were detected by ex vivo ICS. Using mass cytometry, SARS-CoV-2 spike-specific CD8+ T cells were induced and were characterized as having an activated effector memory phenotype. Overall, the results demonstrated a positive correlation between vaccine-induced systemic cytokines, reactogenicity, and adaptive immunity, highlighting the importance of the balance between the induction of innate immunity to achieve vaccine efficacy and ensuring low reactogenicity.

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Safety and immunogenicity of mRNA-LNP COVID-19 vaccine CVnCoV in Latin American adults: A phase 2 randomized study

Cited by 12 publications

References 19 publications

Dendritic cell vaccines improve the glioma microenvironment: Influence, challenges, and future directions

Dendritic cell vaccines improve the glioma microenvironment: Influence, challenges, and future directions

Nanomaterials to combat SARS-CoV-2: Strategies to prevent, diagnose and treat COVID-19

Innate Responses to the Former COVID-19 Vaccine Candidate CVnCoV and Their Relation to Reactogenicity and Adaptive Immunogenicity

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