Evaluating the reactogenicity of COVID-19 vaccines from network-meta analyses

Tiozzo, Giorgia; Louwsma, Timon; Konings, Stefan R A; Vondeling, Gerard T; Gomez, Judith Perez; Postma, Maarten J.; Freriks, Roel

doi:10.1080/14760584.2023.2208216

Cited by 4 publications

(2 citation statements)

References 18 publications

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“…This is similar to the 2.4–3.4% of unexpected splicing events we observed for the C1 and C62 transcriptomes in this work. Since its first use, over 2 billion doses of the ChAdOx1 nCOV-19 vaccine have been administered, particularly in India, South America and Africa, without any reported evidence that rare aberrant splice variants of the spike transcript caused ill effects in vaccine recipients [ 67 , 68 , 69 ].…”

Section: Discussionmentioning

confidence: 99%

Adenovirus Transcriptome in Human Cells Infected with ChAdOx1-Vectored Candidate HIV-1 Vaccine Is Dominated by High Levels of Correctly Spliced HIVconsv1&62 Transgene RNA

et al. 2023

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We develop candidate HIV-1 vaccines, of which two components, ChAdOx1.tHIVconsv1 (C1) and ChAdOx1.HIVconsv62 (C62), are delivered by the simian adenovirus-derived vaccine vector ChAdOx1. Aberrant adenovirus RNA splicing involving transgene(s) coding for the SARS-CoV-2 spike was suggested as an aetiology of rare adverse events temporarily associated with the initial deployment of adenovirus-vectored vaccines during the COVID-19 pandemic. Here, to eliminate this theoretically plausible splicing phenomenon from the list of possible pathomechanisms for our HIV-1 vaccine candidates, we directly sequenced mRNAs in C1- and C62-infected nonpermissive MRC-5 and A549 and permissive HEK293 human cell lines. Our two main observations in nonpermissive human cells, which are most similar to those which become infected after the intramuscular administration of vaccines into human volunteers, were that (i) the dominant adenovirus vector-derived mRNAs were the expected transcripts coding for the HIVconsvX immunogens and (ii) atypical splicing events within the synthetic open reading frame of the two transgenes are rare. We conclude that inadvertent RNA splicing is not a safety concern for the two tested candidate HIV-1 vaccines.

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Section: Discussionmentioning

confidence: 99%

Adenovirus Transcriptome in Human Cells Infected with ChAdOx1-Vectored Candidate HIV-1 Vaccine Is Dominated by High Levels of Correctly Spliced HIVconsv1&62 Transgene RNA

et al. 2023

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“…One of the major challenges for the current mRNA vaccine formulations is vaccine reactogenicity. Many vaccinees have experienced mild to severe systemic adverse effects such as fever, chills and joint pains (reviewed in 1,2 ). Although the precise mechanisms that underlie severe systemic adverse effects are not yet known, it is assumed that excessive innate immune reactions to components of vaccines causes these adverse effects 3 .…”

Section: Introductionmentioning

confidence: 99%

Incorporation of 5 methylcytidine alleviates innate immune response to self-amplifying RNA vaccine

Komori,

Morey,

Quiñones-Molina

et al. 2023

Preprint

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In order to improve vaccine effectiveness and safety profile of existing synthetic RNA-based vaccines, we have developed a self-amplifying RNA (saRNA)-based vaccine expressing membrane-anchored receptor binding domain (RBD) of SARS-CoV-2 S protein (S-RBD) and have demonstrated that a minimal dose of this saRNA vaccine elicits robust immune responses. Results from a recent clinical trial with 5-methylcytidine (5mC) incorporating saRNA vaccine demonstrated reduced vaccine-induced adverse effects while maintaining robust humoral responses. In this study, we investigate the mechanisms accounting for induction of efficient innate and adaptive immune responses and attenuated adverse effects induced by the 5mC-incorporated saRNA. We show that the 5mC-incorporating saRNA platform leads to prolonged and robust expression of antigen, while induction of type-I interferon (IFN-I), a key driver of reactogenicity, is attenuated in peripheral blood mononuclear cells (PBMCs), but not in macrophages and dendritic cells. Interestingly, we find that the major cellular source of IFN-I production in PBMCs is plasmacytoid dendritic cells (pDCs), which is attenuated upon 5mC incorporation in saRNA. In addition, we demonstrate that monocytes also play an important role in amplifying proinflammatory responses. Furthermore, we show that the detection of saRNA is mediated by a host cytosolic RNA sensor, RIG-I. Importantly, 5mC-incorporating saRNA vaccine candidate produced robust IgG responses against S-RBD upon injection in mice, thus providing strong support for the potential clinical use of 5mC-incorporating saRNA vaccines.

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Reactogenicity Differences between COVID-19 Vaccines: A Pro-spective Observational Study in the United States and Canada

Rousculp,

Hollis,

Ziemiecki

et al. 2024

Preprint

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Participants in studies investigating COVID-19 vaccines commonly report reactogenicity events, and concerns about side effects may lead to reluctance to receive updated COVID-19 vaccinations. A real-world, post hoc analysis, observational 2019nCoV-406 study, was conducted to examine reactogenicity within the first 2 days after vaccination with either a protein-based vaccine (NVX-CoV2373) or an mRNA vaccine (BNT162b2 or mRNA-1273) in individuals who previously completed a primary series. Propensity score adjustments were conducted to address potential confounding. The analysis included 1130 participants who received a post–primary series dose of NVX-CoV2373 (n = 303) or an mRNA vaccine (n = 827) during the study period. Within the first 2 days after vaccination, solicited systemic reactogenicity events (adjusted) were reported in 60.5% of participants who received NVX-CoV2373 compared with 84.3% of participants who received an mRNA vaccine; moreover, 33.9% and 61.4%, respectively, reported ≥3 systemic reactogenicity symptoms. The adjusted mean (95% CI) number of systemic symptoms was 1.8 (1.6–2.0) and 3.2 (3.0–3.4), respectively. Local reactogenicity events (adjusted) were reported in 73.4% and 91.7% of participants who received NVX-CoV2373 and mRNA vaccines, respectively; the adjusted mean (95% CI) number of local symptoms was 1.5 (1.33–1.61) and 2.4 (2.31–2.52), respectively. These results support the use of adjuvanted, protein-based NVX-CoV2373 as an immunization option with low reactogenicity.

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Evaluating the reactogenicity of COVID-19 vaccines from network-meta analyses

Cited by 4 publications

References 18 publications

Adenovirus Transcriptome in Human Cells Infected with ChAdOx1-Vectored Candidate HIV-1 Vaccine Is Dominated by High Levels of Correctly Spliced HIVconsv1&62 Transgene RNA

Adenovirus Transcriptome in Human Cells Infected with ChAdOx1-Vectored Candidate HIV-1 Vaccine Is Dominated by High Levels of Correctly Spliced HIVconsv1&62 Transgene RNA

Incorporation of 5 methylcytidine alleviates innate immune response to self-amplifying RNA vaccine

Reactogenicity Differences between COVID-19 Vaccines: A Pro-spective Observational Study in the United States and Canada

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