Vaccines against COVID-19: Priority to mRNA-Based Formulations

Pascolo, Steve

doi:10.3390/cells10102716

Cited by 19 publications

(19 citation statements)

References 56 publications

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“…As a result of an unprecedented worldwide scientific effort, several vaccines against SARS‐CoV‐2 have been developed, relying on the concepts of mRNA‐ or adenovirus vector‐based vaccination, with reported success rates of approximately 90% in phase 3 pivotal trials [ 6 ]. A number of studies have shown that immune response to SARS‐CoV‐2 vaccination is adequate under most DMTs, but consistently found impaired response in pwMS receiving anti‐CD20 and sphingosine‐1‐phosphate receptor modulators (S1PM), although mostly focusing on humoral response [ 7 , 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of vaccination on COVID‐19 outcome in multiple sclerosis

Gradl

Krajnc²,

Hiller³

et al. 2022

Euro J of Neurology

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Background and purpose COVID‐19 continues to challenge neurologists in counseling persons with multiple sclerosis (pwMS) regarding disease‐modifying treatment (DMT) and vaccination. The objective here was to characterize predictors of COVID‐19 outcome in pwMS. Methods We included pwMS with polymerase chain reaction‐confirmed COVID‐19 diagnosis from a nationwide population‐based registry. COVID‐19 outcome was classified as either mild or severe. Impact of DMT, specifically anti‐CD20 monoclonal antibodies (anti‐CD20), and vaccination on COVID‐19 outcome was determined by multivariate models adjusted for a priori risk (determined by a cumulative risk score comprising age, disability, and comorbidities). Results Of 317 pwMS with COVID‐19 (mean age = 41.8 years [SD = 12.4], 72.9% female, median Expanded Disability Status Scale = 1.5 [range = 0–8.5], 77% on DMT [16% on anti‐CD20]), 92.7% had a mild course and 7.3% a severe course, with 2.2% dying from COVID‐19. Ninety‐seven pwMS (30.6%) were fully vaccinated. After a median 5 months from vaccination to SARS‐CoV‐2 infection (range = 1–9), severe COVID‐19 occurred in 2.1% of fully vaccinated pwMS compared to 9.5% in unvaccinated pwMS ( p = 0.018). A priori risk robustly predicted COVID‐19 severity ( R 2 = 0.605, p < 0.001). Adjusting for a priori risk, anti‐CD20 treatment was associated with increased COVID‐19 severity (odds ratio [OR] = 3.3, R 2 = 0.113, p = 0.003), but exposure to any other DMT was not. Fully vaccinated pwMS showed a significantly decreased risk for severe COVID‐19 (OR = 0.21, R 2 = 0.144, p < 0.001). Conclusions In a population‐based MS cohort, COVID‐19 course is primarily predicted by a priori risk (depending on age, disability, and comorbidities) explaining about 60% of variance. Anti‐CD20 treatment is associated with a moderately increased risk, whereas reassuringly vaccination provides protection from severe COVID‐19.

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Section: Introductionmentioning

confidence: 99%

Impact of vaccination on COVID‐19 outcome in multiple sclerosis

Gradl

Krajnc²,

Hiller³

et al. 2022

Euro J of Neurology

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“…Moderna and Pfizer vaccines using a mutated sequence of the receptor-binding domain (RDB) that contains two consecutive prolines, lysine 986, and valine 987 ( 6 ) have been associated with high protection rates ( 7 ). Accumulating evidence demonstrates that the two doses of the BNT162b vaccine elicit either high IgG or neutralizing antibody responses ( 8 , 9 ).…”

Section: Introductionmentioning

confidence: 99%

Cellular and Humoral Immune Responses and Breakthrough Infections After Two Doses of BNT162b Vaccine in Healthcare Workers (HW) 180 Days After the Second Vaccine Dose

Mangia

Serra

Cocomazzi

et al. 2022

Front. Public Health

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BackgroundImmunity and clinical protection induced by mRNA vaccines against SARS-CoV-2 have been shown to decline overtime. To gather information on the immunity profile deemed sufficient in protecting against hospitalization, we tested IgG levels, interferon-gamma (IFN-γ) secretion, and neutralizing antibodies 180 days (d180) after the second shot of BNT162b vaccine, in HW.MethodsA total of 392 subjects were enrolled. All received BioNTech/Pfizer from February 2020 to April 2021. The vaccine-specific humoral response was quantitatively determined by testing for IgG anti-S1 domain of SARS-CoV-spike protein. Live virus microneutralization (MN) was evaluated by an assay performing incubation of serial 2-fold dilution of human serum samples, starting from 1:10 to 1:5120, with an equal volume of Wuhan strain and Delta VOC viral solution and assessing the presence/absence of a cytopathic effect. SARS-CoV-2-spike protein-specific T-cell response was determined by a commercial IFN-γ release assay.ResultsIn 352 individuals, at d180, IgG levels decreased substantially but no results below the assay's positivity threshold were observed. Overall, 22 naive (8.1%) had values above the highest threshold. Among COVID-naive, the impact of age, which was observed at earlier stages, disappeared at d180, while it remained significant for 81 who had experienced a previous infection. Following the predictive model of protection by Khoury, we transformed the neutralizing titers in IU/ml and used a 54 IU/ml threshold to identify subjects with 50% protective immunity. Overall, live virus MN showed almost all subjects with previous exposure to SARS-CoV-2 neutralized the virus as compared to 33% of naive double-dosed subjects (p < 0.0001). All previously exposed subjects had strong IFN-γ secretion (>200 mIU/ml); among 271 naive, 7 (2.58%) and 17 (6.27%) subjects did not show borderline or strong secretion, respectively.ConclusionsIn naive subjects, low IgG titers are relatively long-lasting. Only a third of naive subjects maintain neutralizing responses. After specific stimulation, a very limited number of naive were unable to produce IFN-γ. The results attained in the small group of subjects with breakthrough infection suggest that simultaneous neutralizing antibody titers <20, binding antibody levels/ml <200, and IFN-γ <1,000 mIU/ml in subjects older than 58 may identify at-risk groups.

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“…To date, according to the World Health Organization (WHO), there are currently 73 COVID-19 vaccines that have entered clinical research, and more than 180 remain in preclinical research. The main types include nucleic acid, inactivated, live-attenuated, replicating viral vector vaccines, and virus-like particles vaccines [ 12 ]. Nucleic acid vaccines comprise mRNA and DNA vaccines, which are characterized by simple preparation, safe application, and high efficiency.…”

Section: Introductionmentioning

confidence: 99%

Development of an LNP-Encapsulated mRNA-RBD Vaccine against SARS-CoV-2 and Its Variants

et al. 2022

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Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is undoubtedly the most challenging pandemic in the current century and remains a global health emergency. As the number of COVID-19 cases in the world is on the rise and variants continue to emerge, there is an urgent need for vaccines. Among all immunization approaches, mRNA vaccines have demonstrated more promising results in response to this challenge. Herein, we designed an mRNA-based vaccine encoding the receptor-binding domain (RBD) of SARS-CoV-2 encapsulated in lipid nanoparticles (LNPs). Intramuscular (i.m.) administration of the mRNA-RBD vaccine elicited broad-spectrum neutralizing antibodies and cellular responses against not only the wild-type SARS-CoV-2 virus but also Delta and Omicron variants. These results indicated that two doses of mRNA-RBD immunization conferred a strong immune response in mice against the wild-type SARS-CoV-2, while the booster dose provided a sufficient immunity against SARS-CoV-2 and its variants. Taken together, the three-dose regimen strategy of the mRNA-RBD vaccine proposed in the present study appears to be a promising reference for the development of mRNA vaccines targeting SARS-CoV-2 variants.

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Vaccines against COVID-19: Priority to mRNA-Based Formulations

Cited by 19 publications

References 56 publications

Impact of vaccination on COVID‐19 outcome in multiple sclerosis

Impact of vaccination on COVID‐19 outcome in multiple sclerosis

Cellular and Humoral Immune Responses and Breakthrough Infections After Two Doses of BNT162b Vaccine in Healthcare Workers (HW) 180 Days After the Second Vaccine Dose

Development of an LNP-Encapsulated mRNA-RBD Vaccine against SARS-CoV-2 and Its Variants

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