The association between IgG and IgM antibodies against cardiolipin, β2-glycoprotein I and Domain I of β2-glycoprotein I with disease profile in patients with multiple sclerosis

Antiphospholipid antibodies (aPL) occur in patients with multiple sclerosis (MS) with a number of studies reporting elevated levels; their exact prevalence and pathogenic role remain unclear. Epidemiological studies associate MS with an increased risk of deep venous thromboembolism and stroke; overlapping clinical features with APS. Antibodies against the first domain – Domain I (DI) – of β2glycoprotein I (β2GPI), show the most clinical significance and evidence for pathogenicity in the antiphospholipid syndrome (APS), but have not yet been investigated in MS. Serum from a well-defined cohort of 127 MS patients and 92 healthy controls were tested for IgM and IgG antibodies against cardiolipin (CL), β2GPI and DI. Higher frequency of IgM and IgG anti-CL were found in MS patients (18.1% and 21.3%), compared to controls (1.1% in both cases, p < 0.0001). We report that anti-DI antibodies were associated with MS patients, with 6.3% and 7.1% positive for IgM and IgG, respectively, compared to controls, 1.1% (p < 0.05). IgM anti-CL antibodies were elevated in secondary progressive MS and primary progressive MS compared to relapse-remitting MS, (p < 0.005). This study enrolled the largest number of patients with definite MS for studying the association with aPL. Although we confirmed IgM and IgG anti-CL antibodies occur in patients with MS, this is the first study that identified anti-DI antibodies in MS patients. This new finding may prove valuable and future studies are required to evaluate its role as a potential risk factor of thromboembolic phenomena in MS

Phase I Randomised Clinical Trial of an HIV-1CN54, Clade C, Trimeric Envelope Vaccine Candidate Delivered Vaginally

We conducted a phase 1 double-blind randomised controlled trial (RCT) of a HIV-1 envelope protein (CN54 gp140) candidate vaccine delivered vaginally to assess immunogenicity and safety. It was hypothesised that repeated delivery of gp140 may facilitate antigen uptake and presentation at this mucosal surface. Twenty two healthy female volunteers aged 18–45 years were entered into the trial, the first receiving open-label active product. Subsequently, 16 women were randomised to receive 9 doses of 100 µg of gp140 in 3 ml of a Carbopol 974P based gel, 5 were randomised to placebo solution in the same gel, delivered vaginally via an applicator. Participants delivered the vaccine three times a week over three weeks during one menstrual cycle, and were followed up for two further months. There were no serious adverse events, and the vaccine was well tolerated. No sustained systemic or local IgG, IgA, or T cell responses to the gp140 were detected following vaginal immunisations. Repeated vaginal immunisation with a HIV-1 envelope protein alone formulated in Carbopol gel was safe, but did not induce local or systemic immune responses in healthy women

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe

Adjuvant for vaccination against HIV-1

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Analysis of the relationship between cytokine secretion and proliferative capacity in hepatitis C virus infection.

CD4(+) T-cell responses are important for the outcome of hepatitis C virus (HCV) infection. However, the functional status of HCV-specific CD4(+) T cells in persistent infection is poorly understood. It is generally recognized that proliferative capacity of HCV-specific CD4(+) T cells is weak or absent in persistent infection, but whether this results from deletion of antigen-specific cells or represents maintenance of antigen-specific but poorly proliferative populations is not defined. We used a set of ex vivo assays to evaluate the functionality of HCV specific CD4(+) T cells in persistent and resolved infection. Peripheral blood mononuclear cells (PBMC) from 24 prospectively recruited HCV polymerase chain reaction (PCR) positive individuals, 12 spontaneously resolved individuals (i.e. anti-HCV+, PCR-) and 11 healthy controls were analysed for interferon-gamma (IFN-gamma) and interleukin 2 (IL-2) secretion by enzyme linked immunospot assays (ELISpot). HCV-specific CD4(+) proliferative responses of carboxy fluorescein succinimidyl ester-labelled PBMC were assessed using a sensitive single cell flow cytometric assay. Sustained IFN-gamma ELISpot responses were observed in the PCR+ group. However, proliferation of HCV-specific CD4(+) T cells in the PCR+ group was substantially reduced on a per cell basis, in parallel to IL-2 secretion, compared with responses in the PCR- group. In PCR- individuals, a strong relationship between cytokine secretion and proliferative capacity was seen. However, in PCR+ individuals, IFN-gamma secretion far exceeded proliferative capacity. During persistent HCV infection, some CD4(+) T-cell specificities appear to be lost, as measured using a range of techniques, but others, potentially important, are maintained as IFN-gamma secretors but with low proliferative capacity even using a highly sensitive assay. Such subsets may yet play a significant role in vivo and also provide a template for modulation in immunotherapeutic interventions

HPV prevalence and type distribution in Cypriot women with cervical cytological abnormalities

Abstract Background Human papillomavirus (HPV) is the most common sexually transmitted agent, and it can cause cervical lesions and cancer in females. Currently, information regarding the prevalence of HPV in Cyprus is lacking. The aim of this study was to evaluate the HPV type-specific prevalence in 596 women, aged 19–65 years, with cytological abnormalities. Additionally, in a subset of 348 women for whom cytology results of the Pap test were available, the association between HPV infection and cervical disease was investigated. Methods HPV detection and typing was carried out using PCR and restriction fragment length polymorphism analysis, respectively. Results Overall, the HPV prevalence was 72.8%, and it was shown to be age dependent, with a decreasing prevalence until the age of 45 years (p = 0.0018, χ2). Two hundred and fifty-eight women (59.4%) were infected with high-risk HPV, 151 (34.8%) with low-risk HPV, and 25 (5.8%) with HPV types of unknown risk. The most common high-risk HPV type was HPV16 (17.7%), followed by HPV31 (12.9%), HPV58 (7.1%), HPV68 (4.6%), HPV18 (4.1%), and HPV56 (3.7%). Among the women for whom cytology results were available, 268 (77%) were HPV positive, with a sample distribution as follows: 188 (74%) had atypical squamous cells of undetermined significance (ASCUS), 61 (85.9%) had low-grade squamous intraepithelial lesion (L-SIL), and 19 (82.6%) had high-grade squamous intraepithelial lesion (H-SIL). HPV16 was the most common type among women affected by L-SIL (19.7%) and H-SIL (15.8%), with HPV31 being the most common type in women affected by ASCUS (16.5%). Conclusions The present study provides the first epidemiological data related to HPV prevalence and type distribution in Cypriot women with cytological abnormalities

Evaluation of S1RBD-Specific IgG Antibody Responses following COVID-19 Vaccination in Healthcare Professionals in Cyprus: A Comparative Look between the Vaccines of Pfizer-BioNTech and AstraZeneca

There is an ongoing effort to report data on SARS-CoV-2 antibodies in different individuals. Ninety-seven healthcare workers were enrolled in this study (Pfizer’s BNT162b2, n = 52; and AstraZeneca’s ChAdOx1-S, n = 45) and S1RBD-specific IgG antibodies were analyzed over time. Both vaccines induced S1RBD-specific antibodies after the second dose. A significant increase in S1RBD-specific IgG median levels 3 weeks following the second dose was detected (BNT162b2, 118.0 BAU/mL to 2018.0 BAU/mL; ChAdOx1-S, 38.1 BAU/mL to 182.1 BAU/mL). At 3 months post the second dose, a significant decrease in S1RBD-specific IgG median levels was also evident (BNT162b2, 415.6 BAU/mL, ChAdOx1-S, 84.7 BAU/mL). The elimination rate of these antibodies was faster in BNT162b2- rather than ChAdOx1-S- vaccinated individuals. A booster dose induced a significant increase in the S1RBD-specific IgG median levels (BNT162b2, 1823.0 BAU/mL; ChAdOx1-S, 656.8 BAU/mL). This study is the first of its kind to characterize S1RBD-specific IgG antibody responses in vaccinated healthcare workers in Cyprus. While the positivity for S1RBD-specific antibodies was maintained 3 months after the second vaccine dose, the level of these antibodies waned over the same period, indicating the importance of a booster vaccination. The results herein could complement the public health policies regarding the immunization schedule for COVID-19

Maintenance of HCV-specific T-cell responses in antibody-deficient patients a decade after early therapy.

Early therapy for hepatitis C virus (HCV) is associated with a high rate of viral clearance, but the long-term effects on immune responses remain controversial. The role of antibodies, both acutely and in the long term, is not clearly defined. We investigated these issues in a unique cohort of 7 individuals with primary antibody failure, who had received early interferon therapy after infection through contaminated immunoglobulin therapy a decade previously