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Clinical Infectious Diseases : An... Jun 2024A next-generation Vero cell rabies vaccine (PVRV-NG2) was developed using the same Pitman-Moore strain as in the licensed purified Vero cell vaccine (PVRV; Verorab) and... (Randomized Controlled Trial)
Randomized Controlled Trial
Immunogenicity and Safety of a Purified Vero Rabies Vaccine-Serum Free, Compared With 2 Licensed Vaccines, in a Simulated Rabies Post-Exposure Regimen in Healthy Adults in France: A Randomized, Controlled, Phase 3 Trial.
BACKGROUND
A next-generation Vero cell rabies vaccine (PVRV-NG2) was developed using the same Pitman-Moore strain as in the licensed purified Vero cell vaccine (PVRV; Verorab) and the human diploid cell vaccine (HDCV; Imovax Rabies®).
METHODS
This dual-center, modified, double-blind, phase 3 study evaluated the immunogenic non-inferiority and safety of PVRV-NG2 with and without concomitant intramuscular human rabies immunoglobulin (HRIG) versus PVRV + HRIG and HDCV + HRIG in a simulated post-exposure prophylaxis (PEP) regimen. Healthy adults ≥18 years old (N = 640) were randomized 3:1:1:1 to PVRV-NG2 + HRIG, PVRV + HRIG, HDCV + HRIG, or PVRV-NG2 alone (administered as single vaccine injections on days [D] 0, D3, D7, D14, and 28, with HRIG on D0 in applicable groups). Rabies virus neutralizing antibodies (RVNA) titers were assessed pre- (D0) and post-vaccination (D14, D28, and D42) using the rapid fluorescent focus inhibition test. Non-inferiority, based on the proportion of participants achieving RVNA titers ≥0.5 IU/mL (primary objective), was demonstrated if the lower limit of the 95% CI of the difference in proportions between PVRV-NG2 + HRIG and PVRV + HRIG/HDCV + HRIG was >-5% at D28. Safety was assessed up to 6 months after the last injection.
RESULTS
Non-inferiority of PVRV-NG2 + HRIG compared with PVRV + HRIG and HDCV + HRIG was demonstrated. Nearly all participants (99.6%, PVRV-NG2 + HRIG; 100%, PVRV + HRIG; 98.7%, HDCV + HRIG; 100%, PVRV-NG2 alone) achieved RVNA titers ≥0.5 IU/mL at D28. Geometric mean titers were similar between groups with concomitant HRIG administration at all time points. Safety profiles were similar between PVRV-NG2 and comparator vaccines.
CONCLUSIONS
In a simulated PEP setting, PVRV-NG2 + HRIG showed comparable immunogenicity and safety to current standard-of-care vaccines.
CLINICAL TRIALS REGISTRATION
NCT03965962.
Topics: Humans; Rabies Vaccines; Adult; Male; Rabies; Post-Exposure Prophylaxis; Female; Antibodies, Viral; Double-Blind Method; Middle Aged; Young Adult; Vero Cells; Antibodies, Neutralizing; France; Rabies virus; Animals; Chlorocebus aethiops; Adolescent; Immunogenicity, Vaccine; Healthy Volunteers
PubMed: 38478634
DOI: 10.1093/cid/ciae137 -
Frontiers in Pharmacology 2024Significant attention has been paid to myocardial damage mediated by the single-stranded RNA virus. Qingfei Paidu decoction (QFPDD) has been proved to protect the...
Significant attention has been paid to myocardial damage mediated by the single-stranded RNA virus. Qingfei Paidu decoction (QFPDD) has been proved to protect the damage caused by the influenza virus A/PR/8/1934 (PR8), but its specific mechanism is unclear. Molecular biological methods, together with network pharmacology, were used to analyze the effects and underlying mechanism of QFPDD treatment on PR8-induced myocardial damage to obtain insights into the treatment of COVID-19-mediated myocardial damage. Increased apoptosis and subcellular damage were observed in myocardial cells of mice infected by PR8. QFPDD treatment significantly inhibited the apoptosis and subcellular damage induced by the PR8 virus. The inflammatory factors IFN-β, TNF-α, and IL-18 were statistically increased in the myocardia of the mice infected by PR8, and the increase in inflammatory factors was prevented by QFPDD treatment. Furthermore, the expression levels or phosphorylation of necroptosis-related proteins RIPK1, RIPK3, and MLKL were abnormally elevated in the group of infected mice, while QFPDD restored the levels or phosphorylation of these proteins. Our study demonstrated that HIF-1α is a key target of QFPDD in the treatment of influenza virus-mediated injury. The HIF-α level was significantly increased by PR8 infection. Both the knockdown of HIF-1α and treatment of the myocardial cell with QFPDD significantly reversed the increased inflammatory factors during infection. Overexpression of HIF-1α reversed the inhibition effects of QFPDD on cytokine expression. Meanwhile, seven compounds from QFPDD may target HIF-1α. QFPDD can ameliorate influenza virus-mediated myocardial damage by reducing the degree of cell necroptosis and apoptosis, inhibiting inflammatory response and the expression of HIF-1α. Thus, our results provide new insights into the treatment of respiratory virus-mediated myocardial damage.
PubMed: 38476329
DOI: 10.3389/fphar.2024.1309682 -
Clinical Case Reports Mar 2024Progressive multifocal leukoencephalopathy (PML) is a rare and fatal demyelinating disease of the central nervous system (CNS). The case we describe highlights the...
Progressive multifocal leukoencephalopathy (PML) is a rare and fatal demyelinating disease of the central nervous system (CNS). The case we describe highlights the importance of considering a diagnosis of PML early (<1 year) after lung transplant.
PubMed: 38464572
DOI: 10.1002/ccr3.8626 -
Frontiers in Veterinary Science 2024Transmissible gastroenteritis virus (TGEV) could cause diarrhea, vomiting, dehydration and even death in piglets, miRNA played an important role in the interaction...
Transmissible gastroenteritis virus (TGEV) could cause diarrhea, vomiting, dehydration and even death in piglets, miRNA played an important role in the interaction between virus and cell. The study aimed to investigate the impact of miR-17 on the polysaccharide of Polygonum Cillinerve (PCP) in combating TGEV. miR-17 was screened and transfection validation was performed by Real-time PCR. The function of miR-17 on PK15 cells infected with TGEV and treated with PCP was investigated by DCFH-DA loading probe, JC-1 staining and Hoechst fluorescence staining. Furthermore, the effect of miR-17 on PCP inhibiting TGEV replication and apoptosis signaling pathways during PCP against TGEV infection was measured through Real-time PCR and Western blot. The results showed that miR-17 mimic and inhibitor could be transferred into PK15 cells and the expression of miR-17 significantly increased and decreased respectively compared with miR-17 mimic and inhibitor ( < 0.05). A total 250 μg/mL of PCP could inhibit cells apoptosis after transfection with miR-17. PCP (250 μg/mL and 125 μg/mL) significantly inhibited the decrease in mitochondrial membrane potential induced by TGEV after transfection with miR-17 ( < 0.05). After transfection of miR-17 mimic, PCP at concentrations of 250 μg/mL and 125 μg/mL significantly promoted the mRNA expression of P53, cyt C and caspase 9 ( < 0.05). Compared with the control group, the replication of TGEV gRNA and gene N was significantly inhibited by PCP at concentrations of 250 μg/mL and 125 μg/mL after transfection of both miR-17 mimic and inhibitor ( < 0.05). PCP at 62.5 μg/mL significantly inhibited the replication of gene S following transfection with miR-17 inhibitor ( < 0.05). These results suggested that PCP could inhibit the replication of TGEV and apoptosis induced by TGEV by regulating miR-17.
PubMed: 38444776
DOI: 10.3389/fvets.2024.1360102 -
Frontiers in Neurology 2024A scoping review found that most studies on women's health in multiple sclerosis (MS) focused on pregnancy, fetal/neonatal outcomes and sexual dysfunction. Few studies...
BACKGROUND
A scoping review found that most studies on women's health in multiple sclerosis (MS) focused on pregnancy, fetal/neonatal outcomes and sexual dysfunction. Few studies addressed menopause, contraception, gynecologic cancers/cancer screening. However, the perceived relative importance of these knowledge gaps to people living with MS and other partners is unknown. We engaged a range of partners, including people living with MS, health care providers, researchers, and patient advocacy groups, to set priorities for future research in women's health in MS.
METHODS
We employed a three-step global engagement process. First, we identified which broad research topics relevant to women's health in MS were of highest priority using two surveys. Second, we developed specific research questions within these topics using focus groups. Finally, we prioritized the research questions with a third survey.
RESULTS
Overall, 5,266 individuals responded to the initial surveys [ = 1,430 global survey, mean (SD) age 50.0 (12.6), all continents; = 3,836 North American Research Committee on Multiple Sclerosis survey, mean (SD) age 64.8 (9.6), United States]. Menopause, sexual dysfunction, pregnancy, gynecologic cancer/cancer screening, hormones and parenthood were identified as the most important topics. Focus groups generated 80 potential research questions related to these topics. In the final survey 712 individuals prioritized these questions. The highest priority questions in each research topic were: (i) How do perimenopause and menopause affect disease activity, course, response to disease-modifying treatment and quality of life in MS; (ii) What are the most effective strategies for managing issues around sexual intimacy, including related to low sexual desire, changes in physical function, and MS symptoms; (iii) Are there long-term effects of disease-modifying therapies on the children of persons with MS; (iv) What are the short and long-term effects of disease-modifying drugs on gynecologic cancer risk, particularly for high efficacy disease-modifying drugs and hematopoietic stem cell transplantation; (v) Are there hormone related treatments that can stabilize fluctuations in MS symptoms; and (vi) How does MS fatigue impact parenting strategies.
CONCLUSION
Priorities for research relating to women's health issues for persons with MS have been delineated using a collaborative process with key partners. Alignment of future research with these priorities should be monitored.
PubMed: 38440114
DOI: 10.3389/fneur.2024.1355817 -
Multiple Sclerosis (Houndmills,... Jun 2024The coronavirus disease 2019 (COVID-19) pandemic offered an epidemiological opportunity to evaluate if isolation and masking affected John Cunningham (JC) virus...
BACKGROUND
The coronavirus disease 2019 (COVID-19) pandemic offered an epidemiological opportunity to evaluate if isolation and masking affected John Cunningham (JC) virus transmission.
OBJECTIVE
This study aimed to assess the proportion of natalizumab-treated patients who converted to a positive anti-JCV antibody serostatus before and during the pandemic.
METHODS
Data from TYSABRI Outreach: Unified Commitment to Health (TOUCH) for 22,375 US patients treated with natalizumab with anti-JCV antibody records were assessed in epochs annually from 2017 to 2022.
RESULTS
Pre-pandemic anti-JCV antibody serostatus change was observed for 7.4%-7.7%. During the first and second years of the pandemic, 7.3% and 7.2% of patients' serostatus changed, respectively.
CONCLUSION
The proportion of patients with anti-JCV antibody serostatus change did not significantly differ during the first 2 years of the pandemic compared with prior years. In contrast to seasonal influenza, masking and social distancing had no discernable effect on JCV serostatus change.
Topics: Humans; COVID-19; Multiple Sclerosis; Male; Female; Adult; Physical Distancing; Antibodies, Viral; Middle Aged; United States; JC Virus; Natalizumab; SARS-CoV-2; Immunologic Factors
PubMed: 38406828
DOI: 10.1177/13524585241232274 -
Indian Journal of Pathology &... Nov 2023The incidence of meningoencephalitis (ME) in India is poorly understood, and the exact etiological diagnosis is often not possible. This study was planned to elucidate...
BACKGROUND
The incidence of meningoencephalitis (ME) in India is poorly understood, and the exact etiological diagnosis is often not possible. This study was planned to elucidate the bacterial and viral etiological diagnosis of ME in children less than 5 years of age.
MATERIAL AND METHODS
The present study was conducted in Virus Research and Diagnostic Laboratory (VRDL), Department of Microbiology, King George's Medical University, Lucknow, from July 2020 to June 2022. Serum, cerebrospinal fluid (CSF), and nose/throat swabs were collected from all the enrolled cases of meningoencephalitis in children below 5 years of age and tested for various etiological agents by ELISA and/or real-time PCR.
RESULTS
Of 130 enrolled cases, 50 (38.5%) cases tested positive for one or more etiological agents. Etiological agents of ME detected were Japanese encephalitis virus (JEV) (8.46%), adenovirus (6.92%), influenza virus (5.38%), dengue virus (3.85%), Parvo B-19 virus (3.08%), Orientia tsutsugamushi (3.08%), Herpes Simplex Virus-1 (HSV-1) (1.54%), measles virus (1.54%), and Varicella-Zoster Virus (VZV) (1.54%). Rubella virus, Chikungunya virus (CHKV), Mumps virus, Enteroviruses, Parecho virus, John Cunningham virus (JC), BK virus, Nipah virus, Kyasanur Forest Disease virus (KFD), Chandipura virus, Herpes Simplex Virus (HSV-2), SARS CoV-2, N. Meningitides, and H. Influenzae were tested but not detected in any of the cases.
CONCLUSION
We identified the etiological agents in 50/130 (38.5%) suspected ME cases in children less than 5 years of age, using molecular and ELISA-based diagnostic methods. The four most common pathogens detected were JEV, adenovirus, influenza virus, and dengue virus.
PubMed: 38394398
DOI: 10.4103/ijpm.ijpm_60_23 -
Nature Communications Feb 2024Little is known about the pathobiology of SARS-CoV-2 infection in sub-Saharan Africa, where severe COVID-19 fatality rates are among the highest in the world and the...
Little is known about the pathobiology of SARS-CoV-2 infection in sub-Saharan Africa, where severe COVID-19 fatality rates are among the highest in the world and the immunological landscape is unique. In a prospective cohort study of 306 adults encompassing the entire clinical spectrum of SARS-CoV-2 infection in Uganda, we profile the peripheral blood proteome and transcriptome to characterize the immunopathology of COVID-19 across multiple phases of the pandemic. Beyond the prognostic importance of myeloid cell-driven immune activation and lymphopenia, we show that multifaceted impairment of host protein synthesis and redox imbalance define core biological signatures of severe COVID-19, with central roles for IL-7, IL-15, and lymphotoxin-α in COVID-19 respiratory failure. While prognostic signatures are generally consistent in SARS-CoV-2/HIV-coinfection, type I interferon responses uniquely scale with COVID-19 severity in persons living with HIV. Throughout the pandemic, COVID-19 severity peaked during phases dominated by A.23/A.23.1 and Delta B.1.617.2/AY variants. Independent of clinical severity, Delta phase COVID-19 is distinguished by exaggerated pro-inflammatory myeloid cell and inflammasome activation, NK and CD8 T cell depletion, and impaired host protein synthesis. Combining these analyses with a contemporary Ugandan cohort of adults hospitalized with influenza and other severe acute respiratory infections, we show that activation of epidermal and platelet-derived growth factor pathways are distinct features of COVID-19, deepening translational understanding of mechanisms potentially underlying SARS-CoV-2-associated pulmonary fibrosis. Collectively, our findings provide biological rationale for use of broad and targeted immunotherapies for severe COVID-19 in sub-Saharan Africa, illustrate the relevance of local viral and host factors to SARS-CoV-2 immunopathology, and highlight underemphasized yet therapeutically exploitable immune pathways driving COVID-19 severity.
Topics: Adult; Humans; COVID-19; SARS-CoV-2; Coinfection; Uganda; Pandemics; Prospective Studies; HIV Infections
PubMed: 38368384
DOI: 10.1038/s41467-024-45204-3 -
Clinical Infectious Diseases : An... May 2024Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illnesses in children. RSV can be broadly categorized into 2 major subtypes: A and B. RSV...
Seasonality, Clinical Characteristics, and Outcomes of Respiratory Syncytial Virus Disease by Subtype Among Children Aged <5 Years: New Vaccine Surveillance Network, United States, 2016-2020.
BACKGROUND
Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illnesses in children. RSV can be broadly categorized into 2 major subtypes: A and B. RSV subtypes have been known to cocirculate with variability in different regions of the world. Clinical associations with viral subtype have been studied among children with conflicting findings such that no conclusive relationships between RSV subtype and severity have been established.
METHODS
During 2016-2020, children aged <5 years were enrolled in prospective surveillance in the emergency department or inpatient settings at 7 US pediatric medical centers. Surveillance data collection included parent/guardian interviews, chart reviews, and collection of midturbinate nasal plus/minus throat swabs for RSV (RSV-A, RSV-B, and untyped) using reverse transcription polymerase chain reaction.
RESULTS
Among 6398 RSV-positive children aged <5 years, 3424 (54%) had subtype RSV-A infections, 2602 (41%) had subtype RSV-B infections, and 272 (5%) were not typed, inconclusive, or mixed infections. In both adjusted and unadjusted analyses, RSV-A-positive children were more likely to be hospitalized, as well as when restricted to <1 year. By season, RSV-A and RSV-B cocirculated in varying levels, with 1 subtype dominating proportionally.
CONCLUSIONS
Findings indicate that RSV-A and RSV-B may only be marginally clinically distinguishable, but both subtypes are associated with medically attended illness in children aged <5 years. Furthermore, circulation of RSV subtypes varies substantially each year, seasonally and geographically. With introduction of new RSV prevention products, this highlights the importance of continued monitoring of RSV-A and RSV-B subtypes.
Topics: Humans; Respiratory Syncytial Virus Infections; Seasons; Infant; Child, Preschool; United States; Respiratory Syncytial Virus, Human; Male; Female; Prospective Studies; Hospitalization; Infant, Newborn; Respiratory Syncytial Virus Vaccines
PubMed: 38366649
DOI: 10.1093/cid/ciae085 -
The Lancet. Global Health Mar 2024The first randomised controlled trial of single-dose human papillomavirus (HPV) vaccine efficacy, the Kenya single-dose HPV-vaccine efficacy (KEN SHE) trial, showed...
Comparing one dose of HPV vaccine in girls aged 9-14 years in Tanzania (DoRIS) with one dose in young women aged 15-20 years in Kenya (KEN SHE): an immunobridging analysis of randomised controlled trials.
BACKGROUND
The first randomised controlled trial of single-dose human papillomavirus (HPV) vaccine efficacy, the Kenya single-dose HPV-vaccine efficacy (KEN SHE) trial, showed greater than 97% efficacy against persistent HPV16 and HPV18 infection at 36 months among women in Kenya. We compared antibody responses after one dose of HPV vaccine in the Dose Reduction Immunobridging and Safety Study (DoRIS), the first randomised trial of the single- dose regimen in girls aged 9-14 years, the target age range for vaccination, with those after one dose of the same vaccine in KEN SHE.
METHODS
In the DoRIS trial, 930 girls aged 9-14 years in Tanzania were randomly assigned to one, two, or three doses of the 2-valent vaccine (Cervarix) or the 9-valent vaccine (Gardasil-9). The proportion seroconverting and geometric mean concentrations (GMCs) at month 24 after one dose were compared with those in women aged 15-20 years who were randomly assigned to one dose of the same vaccines at the same timepoint in KEN SHE. Batched samples were tested together by virus-like particle ELISA for HPV16 and HPV18 IgG antibodies. Non-inferiority of GMC ratios (DoRIS trial:KEN SHE) was predefined as a lower bound of the 95% CI less than 0·50.
FINDINGS
Month 24 HPV16 and HPV18 antibody GMCs in DoRIS were similar or higher than those in KEN SHE. 2-valent GMC ratios were 0·90 (95% CI 0·72-1·14) for HPV16 and 1·02 (0·78-1·33) for HPV18. 9-valent GMC ratios were 1·44 (95% CI 1·14-1·82) and 1·47 (1·13-1·90), respectively. Non-inferiority of antibody GMCs and seropositivity was met for HPV16 and HPV18 for both vaccines.
INTERPRETATION
HPV16 and HPV18 immune responses in young girls 24 months after a single dose of 2-valent or 9-valent HPV vaccine were comparable to those in young women who were randomly assigned to a single dose of the same vaccines and in whom efficacy had been shown. A single dose of HPV vaccine, when given to girls in the target age range for vaccination, induces immune responses that could be effective against persistent HPV16 and HPV18 infection at least two years after vaccination.
FUNDING
The UK Department of Health and Social Care, the Foreign, Commonwealth, & Development Office, the Global Challenges Research Fund, the UK Medical Research Council and Wellcome Trust Joint Global Health Trials scheme, the Bill and Melinda Gates Foundation, the US National Cancer Institute; the US National Institutes of Health, and the Francis and Dorothea Reed Endowed Chair in Infectious Diseases.
TRANSLATION
For the KiSwahili translation of the abstract see Supplementary Materials section.
Topics: Female; Humans; Antibodies, Viral; Papillomavirus Infections; Tanzania; Drug Tapering; Kenya; Papillomavirus Vaccines; Human papillomavirus 16; Human papillomavirus 18; Randomized Controlled Trials as Topic
PubMed: 38365419
DOI: 10.1016/S2214-109X(23)00586-7