BACKGROUND: The effect of human papillomavirus (HPV) vaccination on cervical intraepithelial neoplasia grade 2 or worse (CIN2+) recurrence with respect to cone margin positivity is unknown. Most studies assessed this effect beyond two months post-conisation. We aimed to determine both the duration and early onset of effect in women who had been prophylactically vaccinated or vaccinated after conisation, considering cone margin status. METHODS: This cohort study used data from one of the central laboratories in the Czech Republic, covering approximately 33% of women undergoing national cervical cancer screening. It included women treated for CIN2+ between 2010 and 2024 who had received either prophylactic HPV vaccination (available through the national immunisation program since 2011) or post-conisation vaccination (recommended by the Czech Gynaecological and Obstetrical Society since 2008). The vaccination effect was estimated using the incidence rate ratio (IRR) from a Poisson regression model, calculated as 100 × (1-IRR). FINDINGS: Of the 10,054 women enrolled, 919 were vaccinated after conisation, 502 prophylactically, and 169 had undetermined timing of vaccination. Throughout the follow-up period, CIN2+ recurrence was observed in 513 unvaccinated women, with a rate of 14·61 per 1000 person-years (py), in 14 prophylactically vaccinated women, with a rate of 5·84 (54% reduction; 95% confidence interval [CI]: 22-73%), and in 15 women vaccinated post-excision, with a rate of 3·37 (74% reduction; 95% CI: 57-85%). The high recurrence rate of 58·59 per 1000 py within six months of conisation was reduced by 80% (95% CI: 19-95%) with prophylactic vaccination and by 89% (95% CI: 57-97%) with incomplete post-excision vaccination. Among a total of 1771 women with a positive cone margin, recurrence was identified in 272 of 1568 unvaccinated women, corresponding to a recurrence rate of 51·62 per 1000 py. A reduction was observed in 84 prophylactically vaccinated and in 119 women vaccinated post-excision, with only 6 recurrence cases documented in each group. This corresponded to recurrence rates of 14·94 (62% reduction; 95% CI: 14-83%) and 9·78 per 1000 py (79% reduction; 95% CI: 52-90%), respectively. INTERPRETATION: Regardless of timing, HPV vaccination has a beneficial long-term effect in lowering the risk of CIN2+ recurrence. Despite the greater reduction in relapse achieved by post-excision vaccination, the difference compared with the prophylactic one was not statistically significant. The most pronounced benefit was observed within the first six months post-conisation, particularly in women with a positive cone margin. FUNDING: Cooperatio 31 fund, Health Sciences, Charles University, Prague, Czech Republic.
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: The COVID-19 pandemic required rapid development of vaccines within a short period of time which did not allow to assess vaccine effectiveness (VE) in the long-term. METHODS: A computerized literature search was undertaken to identify eligible studies, with no language restrictions, published between 1 December 2020 and 30 June 2023. RESULTS: Out of a total of 27,597 publications, 761 studies were included. Early VE of 87.2% decreased to 55.1% after 9 months among populations fully immunized not only with mRNA (proxy mRNA) vaccines, and 66.3% decreased to 23.5% in populations immunized exclusively with non-mRNA vaccines. Protection against severe COVID-19 declined to 80.9% for proxy mRNA vaccines and 67.2% for non-mRNA vaccines. Omicron variants significantly diminished VE. Within 6-8 months of receiving a single booster of an mRNA vaccine, VE declined to 14.0% and 67.7% for any and severe COVID-19, respectively. Multiple mRNA booster doses restored protection that declined to 29.5% and 70.6% for any and severe COVID-19, respectively, within 5-7 months. CONCLUSION: Outcomes of this meta-regression underscore the evolving nature of COVID-19 in response to vaccination, dosing schedules, and emerging variants, and provide crucial insights for public health interventions and vaccination strategies.
- MeSH
- COVID-19 * epidemiologie prevence a kontrola MeSH
- lidé MeSH
- messenger RNA MeSH
- pandemie MeSH
- SARS-CoV-2 genetika MeSH
- účinnost vakcíny MeSH
- vakcinace MeSH
- vakcíny * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: The main aim was to determine the overall vaccine effectiveness (VE) against recurrent cervical intraepithelial neoplasia grade 2 or worse (CIN2+) including specific VE associated with timing of human papillomavirus (HPV) vaccination using data from published studies. DESIGN: Meta-analysis and meta-regression. DATA SOURCES: A computerised literature search was undertaken using the MEDLINE, EMBASE, International Pharmaceutical Abstracts, Derwent Drug File, ProQuest Science and Technology, Cochrane and MedRxiv databases. To be eligible, the studies, with no language restrictions, had to be published between 1 January 2001 and 25 May 2023. REVIEW METHODS: Included were studies with an unvaccinated reference group that assessed CIN2+ recurrence irrespective of the HPV genotype in women undergoing conisation provided. The present study was carried out in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analyses and Meta-analysis Of Observational Studies in Epidemiology guidelines. The risk of study bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. The Grading of Recommendations Assessment, Development, and Evaluation guidelines were used to assess the strength of evidence for the primary outcome. Data synthesis was conducted using meta-analysis and meta-regression. RESULTS: Out of a total of 14 322 publications, 20 studies with a total of 21 estimates were included. The overall VE against recurrent CIN2+ irrespective of the HPV genotype achieved 69.5% (95% CI: 54.7% to 79.5%). While the HPV vaccine valency, follow-up duration, type of study including its risk of bias had no effect on VE, the highest VE of 78.1% (95% CI: 68.7% to 84.7%) was reported for women receiving their first dose not earlier than the day of excision. This outcome was supported by additional analyses and a VE prediction interval ranging from 67.1% to 85.4%. CONCLUSIONS: The outcome of this meta-analysis and meta-regression convincingly showed the beneficial effect of post-excisional HPV vaccination against CIN2+ recurrence. Studies published to date have been unable to determine whether or not vaccination, completed or initiated before conisation, would be associated with more favourable results. PROSPERO REGISTRATION NUMBER: CRD42022353530.
- MeSH
- dysplazie děložního hrdla * MeSH
- infekce papilomavirem * MeSH
- lidé MeSH
- nádory děložního čípku * prevence a kontrola chirurgie MeSH
- vakcinace MeSH
- vakcíny proti papilomavirům * MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
BACKGROUND: Observational studies made it possible to assess the impact of risk factors on the long-term effectiveness of mRNA and adenoviral vector (AdV) vaccines against COVID-19. METHODS: A computerized literature search was undertaken using the MEDLINE, EMBASE, and MedRxiv databases to identify eligible studies, with no language restrictions, published up to 28 February 2022. Eligible were observational studies assessing vaccine effectiveness (VE) by disease severity with reference groups of unvaccinated participants or participants immunized with one, two, or three vaccine doses. Our study was carried out in compliance with the PRISMA and MOOSE guidelines. The risk of study bias was identified using the Newcastle-Ottawa Quality Assessment Scale. The GRADE guidelines were applied to assess the strength of evidence for the primary outcome. The synthesis was conducted using a meta-analysis and meta-regression. RESULTS: Out of a total of 14,155 publications, 290 studies were included. Early VE of full vaccination against COVID-19 of any symptomatology and severity decreased from 96% (95% CI, 95-96%) for mRNA and from 86% (95% CI, 83-89%) for AdV vaccines to 67% for both vaccine types in the last 2 months of 2021. A similar 1-year decline from 98 to 86% was found for severe COVID-19 after full immunization with mRNA, but not with AdV vaccines providing persistent 82-87% effectiveness. Variant-reduced VE was only associated with Omicron regardless of disease severity, vaccine type, or vaccination completeness. The level of protection was reduced in participants aged >65 years, with a comorbidity or those in long-term care or residential homes independently of the number of doses received. The booster effect of the third mRNA dose was unclear because incompletely restored effectiveness, regardless of disease severity, declined within a short-term interval of 4 months. CONCLUSIONS: Full vaccination provided an early high, yet waning level of protection against COVID-19 of any severity with a strong impact on the high-risk population. Moreover, the potential risk of new antigenically distinct variants should not be underestimated, and any future immunization strategy should include variant-updated vaccines.
Immunological memory is the ability of the adaptive immune system to ensure a persistent protective effect after immunization. However, it can also be a limitation to building a sufficient level of protective antibodies specific to new mutations of the virus. It is imperative to bear this phenomenon (called "original antigenic sin") in mind and make every effort to overcome its inherent pitfalls when updating current and designing new vaccines.
- MeSH
- antigeny MeSH
- COVID-19 * prevence a kontrola MeSH
- lidé MeSH
- SARS-CoV-2 * MeSH
- vakcinace MeSH
- vakcíny proti COVID-19 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Continuous assessment of the effectiveness of approved COVID-19 vaccines is crucial to gain an insight into the longer-term impact on health outcomes, and eventually boosting public confidence. For this reason, we conducted a multicenter, retrospective cohort study using data on infection and vaccination rates among employees of three Prague hospitals in the period between 27 December 2020 and 31 August 2021. The post-vaccination and post-infection protectiveness were assessed in a total of 11,443 hospital workers who were followed up for more than 14 days either after their Comirnaty vaccination or study enrolment, depending on their previous SARS-CoV-2 infection. The effectiveness of full vaccination against any SARS-CoV-2 infection achieved 88.3% (83.2-91.8%) over the eight months of follow-up, a figure not much different from the 92.5% (76.5-97.6%) level of protection built by a previous infection. Despite this, the post-vaccination level of protection declined to about 65% between June and August. No case of breakthrough infection was registered among hospital workers having received one or two vaccine doses more than three months after previous infection. The eight-month effectiveness of the Comirnaty vaccine exhibited a declining trend requiring a new booster dose. The need for vaccination in the previously infected employees was not demonstrated conclusively in this study.
- Publikační typ
- časopisecké články MeSH
- MeSH
- COVID-19 * MeSH
- lidé MeSH
- protilátky virové MeSH
- SARS-CoV-2 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- metaanalýza MeSH
Vaccination as an important tool in the fight against infections has been suggested as a possible trigger of autoimmunity over the last decades. To confirm or refute this assumption, a Meta-analysis of Autoimmune Disorders Association With Immunization (MADAWI) was conducted. Included in the meta-analysis were a total of 144 studies published in 1968-2019 that were available in six databases and identified by an extensive literature search conducted on 30 November 2019. The risk of bias classification of the studies was performed using the Newcastle-Ottawa Quality Assessment Scale. The strength of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation. While our primary analysis was conducted in terms of measures of association employed in studies with a low risk of bias, the robustness of the MADAWI outcome was tested using measures independent of each study risk of bias. Additionally, subgroup analyses were performed to determine the stability of the outcome. The pooled association of 0.99 (95% confidence interval, 0.97-1.02), based on a total of 364 published estimates, confirmed an equivalent occurrence of autoimmune disorders in vaccinated and unvaccinated persons. The same level of association reported by studies independently of the risk of bias was supported by a sufficient number of studies, and no serious limitation, inconsistency, indirectness, imprecision, and publication bias. A sensitivity analysis did not reveal any discrepancy in the primary result. Current common vaccination is not the cause of any of the examined autoimmune disorders in the medium and long terms.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Nová pandemie způsobená virem SARS-CoV-2, rozšířeným po celém světě, od počátku loňského roku 2020 vyvolala potřebu rychle vyvinout odpovídající vakcínu, která by byla dostupná pro celosvětovou populaci. Od počátku bylo zřejmé, že jedna vakcína stačit nebude. Tohoto pomyslného úkolu se zhostilo mnoho vývojových laboratoří po celém světě a navrhly různé typy vakcín, tj. inaktivované celovirionové, subjednotkové, živé nebo vektorové a genetické. Právě ten posledně uvedený typ získal pomyslné prvenství v rychlosti vývoje, výroby a klinického hodnocení a stal se na počátku ledna 2021 dostupným v zemích Evropské unie. Genetické mRNA vakcíny nebyly dosud používány v rámci běžného očkování používány, a proto si zaslouží zvýšenou pozornost. Tato práce předkládá souhrn stávajících poznatků o mechanismu, účinnosti a bezpečnosti očkování genetickými mRNA vakcínami.
A new pandemic caused by the worldwide spread SARS-CoV-2 since the beginning of the last year 2020 has evoked the need to rapidly develop an appropriate vaccine that would be available to the global population. From the beginning, it was clear that one vaccine would not be enough. Many development laboratories around the world have undertaken this task and they have designed various types of vaccines, i.e. inactivated whole-virus, subunit, live or vector and genetic ones. It was the genetic vaccine that won the imaginary lead in the speed of development, production and clinical trials and it has become available in the countries of the European Union in the beginning of 2021. Genetic mRNA vaccines have not yet been used in routine vaccination and therefore they deserve increased attention. This work presents a summary of current knowledge about the mechanism, efficacy and safety of vaccination with genetic mRNA vaccines.
