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JAMA Network Open Jul 2024In the context of emerging SARS-CoV-2 variants or lineages and new vaccines, it is key to accurately monitor COVID-19 vaccine effectiveness (CVE) to inform vaccination...
IMPORTANCE
In the context of emerging SARS-CoV-2 variants or lineages and new vaccines, it is key to accurately monitor COVID-19 vaccine effectiveness (CVE) to inform vaccination campaigns.
OBJECTIVE
To estimate the effectiveness of COVID-19 vaccines administered in autumn and winter 2022 to 2023 against symptomatic SARS-CoV-2 infection (with all circulating viruses and XBB lineage in particular) among people aged 60 years or older in Europe, and to compare different CVE approaches across the exposed and reference groups used.
DESIGN, SETTING, AND PARTICIPANTS
This case-control study obtained data from VEBIS (Vaccine Effectiveness, Burden and Impact Studies), a multicenter study that collects COVID-19 and influenza data from 11 European sites: Croatia; France; Germany; Hungary; Ireland; Portugal; the Netherlands; Romania; Spain, national; Spain, Navarre region; and Sweden. Participants were primary care patients aged 60 years or older with acute respiratory infection symptoms who were recruited at the 11 sites after the start of the COVID-19 vaccination campaign from September 2022 to August 2023. Cases and controls were defined as patients with positive and negative, respectively, reverse transcription-polymerase chain reaction (RT-PCR) test results.
EXPOSURES
The exposure was COVID-19 vaccination. The exposure group consisted of patients who received a COVID-19 vaccine during the autumn and winter 2022 to 2023 vaccination campaign and 14 days or more before symptom onset. Reference group included patients who were not vaccinated during or in the 6 months before the 2022 to 2023 campaign (seasonal CVE), those who were never vaccinated (absolute CVE), and those who were vaccinated with at least the primary series 6 months or more before the campaign (relative CVE). For relative CVE of second boosters, patients receiving their second booster during the campaign were compared with those receiving 1 booster 6 months or more before the campaign.
MAIN OUTCOMES AND MEASURES
The outcome was RT-PCR-confirmed, medically attended, symptomatic SARS-CoV-2 infection. Four CVE estimates were generated: seasonal, absolute, relative, and relative of second boosters. CVE was estimated using logistic regression, adjusting for study site, symptom onset date, age, chronic condition, and sex.
RESULTS
A total of 9308 primary care patients were included, with 1687 cases (1035 females; median [IQR] age, 71 [65-79] years) and 7621 controls (4619 females [61%]; median [IQR] age, 71 [65-78] years). Within 14 to 89 days after vaccination, seasonal CVE was 29% (95% CI, 14%-42%), absolute CVE was 39% (95% CI, 6%-60%), relative CVE was 31% (95% CI, 15% to 44%), and relative CVE of second boosters was 34% (95% CI, 18%-47%) against all SARS-CoV-2 variants. In the same interval, seasonal CVE was 44% (95% CI, -10% to 75%), absolute CVE was 52% (95% CI, -23% to 82%), relative CVE was 47% (95% CI, -8% to 77%), and relative CVE of second boosters was 46% (95% CI, -13% to 77%) during a period of high XBB circulation. Estimates decreased with time since vaccination, with no protection from 180 days after vaccination.
CONCLUSIONS AND RELEVANCE
In this case-control study among older Europeans, all CVE approaches suggested that COVID-19 vaccines administered in autumn and winter 2022 to 2023 offered at least 3 months of protection against symptomatic, medically attended, laboratory-confirmed SARS-CoV-2 infection. The effectiveness of new COVID-19 vaccines against emerging SARS-CoV-2 variants should be continually monitored using CVE seasonal approaches.
Topics: Humans; Aged; COVID-19; COVID-19 Vaccines; Female; Europe; Male; Vaccine Efficacy; SARS-CoV-2; Seasons; Middle Aged; Case-Control Studies; Aged, 80 and over; Vaccination; European People
PubMed: 38949812
DOI: 10.1001/jamanetworkopen.2024.19258 -
BioRxiv : the Preprint Server For... Jun 2024It is not clear whether human progression to active tuberculosis disease (TB) risk signatures are viable endpoint criteria for evaluations of treatments in clinical or...
UNLABELLED
It is not clear whether human progression to active tuberculosis disease (TB) risk signatures are viable endpoint criteria for evaluations of treatments in clinical or preclinical development. TB is the deadliest infectious disease globally and more efficacious vaccines are needed to reduce this mortality. However, the immune correlates of protection for either preventing infection with or preventing TB disease have yet to be completely defined, making the advancement of candidate vaccines through the pipeline slow, costly, and fraught with risk. Human-derived correlate of risk (COR) gene signatures, which identify an individual's risk to progressing to active TB disease, provide an opportunity for evaluating new therapies for TB with clear and defined endpoints. Though prospective clinical trials with longitudinal sampling are prohibitively expensive, characterization of COR gene signatures is practical with preclinical models. Using a 3Rs (Replacement, Reduction and Refinement) approach we reanalyzed heterogeneous publicly available transcriptional datasets to determine whether a specific set of COR signatures are viable endpoints in the preclinical pipeline. We selected RISK6, Sweeney3 and BATF2 human-derived blood-based RNA biosignatures because they require relatively few genes to assign a score and have been carefully evaluated across several clinical cohorts. Excitingly, these data provide proof-of-concept that human COR signatures seem to have high fidelity across several tissue types in the preclinical TB model pipeline and show best performance when the model most closely reflected human infection or disease conditions. Human-derived COR signatures offer an opportunity for high-throughput preclinical endpoint criteria of vaccine and drug therapy evaluations.
ONE SENTENCE SUMMARY
Human-derived biosignatures of tuberculosis disease progression were evaluated for their predictive fidelity across preclinical species and derived tissues using available public data sets.
PubMed: 38948876
DOI: 10.1101/2024.06.21.600067 -
Frontiers in Endocrinology 2024Studies on the effect of vaccine type and two other vaccines other than inactivated vaccines approved in China on fertilization (IVF) pregnancy outcomes are rare. To...
INTRODUCTION
Studies on the effect of vaccine type and two other vaccines other than inactivated vaccines approved in China on fertilization (IVF) pregnancy outcomes are rare. To complement and confirm the existing findings, this research aimed to investigate whether there are adverse effects of different vaccine types in females and males on reproductive function and clinical pregnancy.
METHODS
This retrospective study enrolled 6,455 fresh embryo transfer cycles at the First Affiliated Hospital of Zhengzhou University between May 1, 2021, and October 31, 2022. The primary outcome is the clinical pregnancy rate (CPR). At the same time, the secondary results are the number of oocytes retrieved, two pronuclei (2PN) rate, blastocyst formation rate, high-quality blastocyst rate, and semen parameters (volume, density, sperm count, forward motility rate, total motility rate, immobility rate, and DNA fragment index (DFI) rate).
RESULTS
In the comparison of ovarian stimulation indicators, no statistically significant differences (P > 0.05) were found in Gn days, endometrial thickness, 2PN rate, metaphase 2 (MII) rate, high-quality embryo rate, and blastocyst formation rate. No significant differences (P>0.05) were found in age, body mass index (BMI), education level, and semen parameters (volume, density, sperm count, forward motility rate, total motility rate, immobility rate, and DFI rate) in these four groups. The multivariate regression model showed that neither the types of vaccines nor the vaccination status of both infertile couples significantly affected clinical pregnancy.
DISCUSSION
The type of vaccine does not appear to have an unfavorable effect on ovarian stimulation, embryo development, semen parameters, and clinical pregnancy.
Topics: Humans; Female; Pregnancy; Male; Retrospective Studies; Adult; Pregnancy Outcome; COVID-19 Vaccines; COVID-19; Pregnancy Rate; Infertility; Fertilization in Vitro; Vaccination; Ovulation Induction; Reproduction; Embryo Transfer; China; SARS-CoV-2
PubMed: 38948529
DOI: 10.3389/fendo.2024.1356938 -
ArXiv Jun 2024Neoantigen targeting therapies including personalized vaccines have shown promise in the treatment of cancers, particularly when used in combination with checkpoint...
BACKGROUND
Neoantigen targeting therapies including personalized vaccines have shown promise in the treatment of cancers, particularly when used in combination with checkpoint blockade therapy. At least 100 clinical trials involving these therapies are underway globally. Accurate identification and prioritization of neoantigens is highly relevant to designing these trials, predicting treatment response, and understanding mechanisms of resistance. With the advent of massively parallel DNA and RNA sequencing technologies, it is now possible to computationally predict neoantigens based on patient-specific variant information. However, numerous factors must be considered when prioritizing neoantigens for use in personalized therapies. Complexities such as alternative transcript annotations, various binding, presentation and immunogenicity prediction algorithms, and variable peptide lengths/registers all potentially impact the neoantigen selection process. There has been a rapid development of computational tools that attempt to account for these complexities. While these tools generate numerous algorithmic predictions for neoantigen characterization, results from these pipelines are difficult to navigate and require extensive knowledge of the underlying tools for accurate interpretation. This often leads to over-simplification of pipeline outputs to make them tractable, for example limiting prediction to a single RNA isoform or only summarizing the top ranked of many possible peptide candidates. In addition to variant detection, gene expression and predicted peptide binding affinities, recent studies have also demonstrated the importance of mutation location, allele-specific anchor locations, and variation of T-cell response to long versus short peptides. Due to the intricate nature and number of salient neoantigen features, presenting all relevant information to facilitate candidate selection for downstream applications is a difficult challenge that current tools fail to address.
RESULTS
We have created pVACview, the first interactive tool designed to aid in the prioritization and selection of neoantigen candidates for personalized neoantigen therapies including cancer vaccines. pVACview has a user-friendly and intuitive interface where users can upload, explore, select and export their neoantigen candidates. The tool allows users to visualize candidates across three different levels, including variant, transcript and peptide information.
CONCLUSIONS
pVACview will allow researchers to analyze and prioritize neoantigen candidates with greater efficiency and accuracy in basic and translational settings The application is available as part of the pVACtools pipeline at pvactools.org and as an online server at pvacview.org.
PubMed: 38947921
DOI: No ID Found -
Frontiers in Immunology 2024A maternal vaccine to protect newborns against invasive infection is a developing medical need. The vaccine should be offered during the third trimester of pregnancy... (Review)
Review
A maternal vaccine to protect newborns against invasive infection is a developing medical need. The vaccine should be offered during the third trimester of pregnancy and induce strong immune responses and placental transfer of protective antibodies. Polysaccharide vaccines against conjugated to protein carriers are in advanced stages of development. Additionally, protein-based vaccines are also in development, showing great promise as they can provide protection regardless of serotype. Furthermore, safety concerns regarding a new vaccine are the main barriers identified. Here, we present vaccines in development and identified safety, cost, and efficacy concerns, especially in high-need, low-income countries.
Topics: Streptococcus agalactiae; Humans; Streptococcal Infections; Streptococcal Vaccines; Pregnancy; Female; Animals; Pregnancy Complications, Infectious; Vaccine Development; Infant, Newborn; Antibodies, Bacterial
PubMed: 38947337
DOI: 10.3389/fimmu.2024.1430901 -
Frontiers in Immunology 2024The One Health approach, which integrates the health of humans, animals, plants, and ecosystems at various levels, is crucial for addressing interconnected health... (Review)
Review
The One Health approach, which integrates the health of humans, animals, plants, and ecosystems at various levels, is crucial for addressing interconnected health threats. This is complemented by the advent of mRNA vaccines, which have revolutionized disease prevention. They offer broad-spectrum effectiveness and can be rapidly customized to target specific pathogens. Their utility extends beyond human medicine, showing potential in veterinary practices to control diseases and reduce the risk of zoonotic transmissions. This review place mRNA vaccines and One Health in the context of tick-borne diseases. The potential of these vaccines to confer cross-species immunity is significant, potentially disrupting zoonotic disease transmission cycles and protecting the health of both humans and animals, while reducing tick populations, infestations and circulation of pathogens. The development and application of mRNA vaccines for tick and tick-borne pathogens represent a comprehensive strategy in global health, fostering a healthier ecosystem for all species in our interconnected world.
Topics: Animals; Humans; Tick-Borne Diseases; Ticks; mRNA Vaccines; One Health; Zoonoses; RNA, Messenger; Vaccines, Synthetic
PubMed: 38947333
DOI: 10.3389/fimmu.2024.1384442 -
Research Square Jun 2024The unprecedented scientific response to the SARS-Cov-2 pandemic in 2020 required the rapid development and activation of extensive clinical trial networks to study...
BACKGROUND
The unprecedented scientific response to the SARS-Cov-2 pandemic in 2020 required the rapid development and activation of extensive clinical trial networks to study vaccines and therapeutics. The COVID-19 Prevention Network (CoVPN) coordinated hundreds of sites conducting phase 2 and 3 clinical trials of vaccines and antibody therapeutics. To facilitate these clinical trials, the CoVPN Volunteer Screening Registry (VSR) was created to collect volunteer information at scale, identify volunteers at risk of COVID-19 who met enrollment criteria, distribute candidates across clinical trial sites, and enable monitoring of volunteering and enrollment progress.
METHODS
We developed a secure database to support three primary web-based interfaces: a national volunteer questionnaire intake form, a clinical trial site portal, and an Administrative Portal. The Site Portal supported filters based on volunteer attributes, visual analytics, enrollment status tracking, geographic search, and clinical risk prediction. The Administrative Portal supported oversight and development with pre-specified reports aggregated by geography, trial, and trial site; charts of volunteer rates over time; volunteer risk score calculation; and dynamic, user-defined reports.
FINDINGS
Over 650,000 volunteers joined the VSR, and 1094 users were trained to utilize the system. The VSR played a key role in recruitment for the Moderna, Oxford-AstraZeneca, Janssen, and Novavax vaccine clinical trials, provided support to the Pfizer and Sanofi vaccine and prophylactic antibody clinical trials, and enhanced the diversity of trial participants. Clinical trial sites selected 166,729 volunteer records for follow-up screening, and of these 47·7% represented groups prioritized for increased enrollment. Despite the unprecedented urgency of its development, the system maintained 99·99% uptime.
INTERPRETATION
The success of the VSR demonstrates that information tools can be rapidly yet safely developed through a public-private partnership and integrated into a distributed and accelerated clinical trial setting. We further summarize the requirements, design, and development of the system, and discuss lessons learned for future pandemic preparedness.
PubMed: 38947011
DOI: 10.21203/rs.3.rs-4397271/v1 -
Research Square Jun 2024Tauopathies, including Alzheimer's disease (AD) and Frontotemporal Dementia (FTD), are histopathologically defined by the aggregation of hyperphosphorylated pathological...
Virus-like particle (VLP)-based vaccine targeting tau phosphorylated at Ser396/Ser404 (PHF1) site outperforms phosphorylated S199/S202 (AT8) site in reducing tau pathology and restoring cognitive deficits in the rTg4510 mouse model of tauopathy.
Tauopathies, including Alzheimer's disease (AD) and Frontotemporal Dementia (FTD), are histopathologically defined by the aggregation of hyperphosphorylated pathological tau (pTau) as neurofibrillary tangles in the brain. Site-specific phosphorylation of tau occurs early in the disease process and correlates with progressive cognitive decline, thus serving as targetable pathological epitopes for immunotherapeutic development. Previously, we developed a vaccine (Qβ-pT181) displaying phosphorylated Thr181 tau peptides on the surface of a Qβ bacteriophage virus-like particle (VLP) that induced robust antibody responses, cleared pathological tau, and rescued memory deficits in a transgenic mouse model of tauopathy. Here we report the characterization and comparison of two additional Qβ VLP-based vaccines targeting the dual phosphorylation sites Ser199/Ser202 (Qβ-AT8) and Ser396/Ser404 (Qβ-PHF1). Both Qβ-AT8 and Qβ-PHF1 vaccines elicited high-titer antibody responses against their pTau epitopes. However, only Qβ-PHF1 rescued cognitive deficits, reduced soluble and insoluble pathological tau, and reactive microgliosis in a 4-month rTg4510 model of FTD. Both sera from Qβ-AT8 and Qβ-PHF1 vaccinated mice were specifically reactive to tau pathology in human AD post-mortem brain sections. These studies further support the use of VLP-based immunotherapies to target pTau in AD and related tauopathies and provide potential insight into the clinical efficacy of various pTau epitopes in the development of immunotherapeutics.
PubMed: 38946961
DOI: 10.21203/rs.3.rs-4390998/v1 -
Progress in Community Health... 2024Incarcerated people have been disproportionately affected by the COVID-19 pandemic and face significant challenges to COVID-19 vaccine confidence.
BACKGROUND
Incarcerated people have been disproportionately affected by the COVID-19 pandemic and face significant challenges to COVID-19 vaccine confidence.
OBJECTIVES
(1) Describe our partnerships with community members directly impacted by incarceration, (2) discuss the partnership's process for co-developing and implementing project interventions to increase COVID-19 vaccine confidence, and (3) share lessons learned from this unique community-engaged partnership.
METHODS
An advisory board of 14 formerly incarcerated community members participated in this project. Their wisdom and experience led to the development and implementation of interventions to increase confidence in COVID-19 vaccines among incarcerated people.
LESSONS LEARNED
Valuable lessons learned were centering community, leaning into trusted sources of information, acknowledging historical and present harms, and investing in community-engaged work.
CONCLUSIONS
Centering lived experiences of those directly impacted by incarceration has been crucial to increasing vaccine confidence among this population. Doing so reinforced the importance of long-term investments in community-based collaborations with communities impacted by incarceration.
Topics: Humans; COVID-19 Vaccines; COVID-19; Prisoners; Prisons; Community-Based Participatory Research; Jails; SARS-CoV-2
PubMed: 38946565
DOI: No ID Found -
Immunology and Cell Biology Jun 2024In this article for the Highlight of 2023 series, we discuss recent advances in the fundamental biology of the germinal center response. These discoveries provide...
In this article for the Highlight of 2023 series, we discuss recent advances in the fundamental biology of the germinal center response. These discoveries provide important insights as to how the germinal center contributes to protection against infection, and also highlights opportunities for future vaccine development.
PubMed: 38946158
DOI: 10.1111/imcb.12800