Broad and potent neutralizing antibodies are elicited in vaccinated individuals following Delta/BA.1 breakthrough infection.

With the emergence of SARS-CoV-2 viral variants, there has been an increase in infections in vaccinated individuals. Here, we isolated monoclonal antibodies (mAbs) from individuals experiencing a breakthrough infection (Delta or BA.1) to determine how exposure to a heterologous Spike broadens the neutralizing antibody response at the monoclonal level.

The effect of Omicron breakthrough infection and extended BNT162b2 booster dosing on neutralization breadth against SARS-CoV-2 variants of concern.

COVID-19 vaccines are playing a vital role in controlling the COVID-19 pandemic. As SARS-CoV-2 variants encoding mutations in the surface glycoprotein, Spike, continue to emerge, there is increased need to identify immunogens and vaccination regimens that provide the broadest and most durable immune responses. We compared the magnitude and breadth of the neutralizing antibody response, as well as levels of Spike-reactive memory B cells, in individuals receiving a second dose of BNT162b2 at a short (3-4 week) or extended interval (8-12 weeks) and following a third vaccination approximately 6-8 months later.

ChAdOx1 nCoV-19 vaccine elicits monoclonal antibodies with cross-neutralizing activity against SARS-CoV-2 viral variants.

Although the antibody response to COVID-19 vaccination has been studied extensively at the polyclonal level using immune sera, little has been reported on the antibody response at the monoclonal level. Here, we isolate a panel of 44 anti-SARS-CoV-2 monoclonal antibodies (mAbs) from an individual who received two doses of the ChAdOx1 nCoV-19 (AZD1222) vaccine at a 12-week interval. We show that, despite a relatively low serum neutralization titer, Spike-reactive IgG+ B cells are still detectable 9 months post-boost.

Author Correction: A dynamic COVID-19 immune signature includes associations with poor prognosis.

A Correction to this paper has been published: https://doi.org/10.1038/s41591-020-01186-5.

Author Correction: A dynamic COVID-19 immune signature includes associations with poor prognosis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A dynamic COVID-19 immune signature includes associations with poor prognosis.

Improved understanding and management of COVID-19, a potentially life-threatening disease, could greatly reduce the threat posed by its etiologic agent, SARS-CoV-2. Toward this end, we have identified a core peripheral blood immune signature across 63 hospital-treated patients with COVID-19 who were otherwise highly heterogeneous. The signature includes discrete changes in B and myelomonocytic cell composition, profoundly altered T cell phenotypes, selective cytokine/chemokine upregulation and SARS-CoV-2-specific antibodies.

Early antiretroviral therapy reduces HIV DNA following perinatal HIV infection.

: The impact of antiretroviral therapy (ART) on the size of the HIV reservoir has implications for virological remission in adults, but is not well characterized in perinatally acquired infection. In a prospective observational study of 20 children with perinatally acquired infection and sustained viral suppression on ART for more than 5 years, proviral DNA was significantly higher in deferred (>4 years) versus early (first year of life) ART recipients (P = 0.0062), and correlated with age of initiation (P = 0.

Short Communication: Lack of Effect of Maraviroc Intensification on Blood and Gut Reservoir.

We show that intensification of treatment with maraviroc in patients chronically infected with HIV-1 receiving successful long-term antiretroviral therapy was not associated with improvements in HIV-related morbidity, HIV reservoir, microbial translocation, immune activation, or immune exhaustion in either gut or peripheral blood. The measurement of reservoir in both gut and blood longitudinally contributes to a paucity of data in the area.

Effects on vitamin D, bone and the kidney of switching from fixed-dose tenofovir disoproxil fumarate/emtricitabine/efavirenz to darunavir/ritonavir monotherapy: a randomized, controlled trial (MIDAS).

Background: Efavirenz (EFV) has been associated with reductions in vitamin D (25[OH]D) and tenofovir (TDF) with increased bone turnover, reductions in bone mineral density (BMD) and renal tubular dysfunction. We hypothesized that switching from fixed-dose TDF/emtricitabine (FTC)/EFV to darunavir/ritonavir monotherapy (DRV/r) might increase 25(OH)D and BMD, and improve renal tubular function.

Methods: Subjects with HIV RNA <50 copies/ml on TDF/FTC/EFV for ≥6 months were randomized 1:1 to ongoing TDF/FTC/EFV or DRV/r (800/100 mg once daily) for 48 weeks.

Bridging the financial gap through providing contract services: a model for publicly funded clinical biobanks.

Biobanks offer translational researchers a novel method of obtaining clinical research materials, patient data, and relevant ethical and legal permissions. However, such tissue collections are expensive to establish and maintain. Current opinion is that such initiatives can only survive with core funding from Government or major funding bodies.

Variation of Peripheral Blood Mononuclear Cell RNA Quality in Archived Samples.

The Infectious Diseases BioBank (IDB) has consistently archived peripheral blood mononuclear cell (PBMNC) RNA for transcriptome analyses. RNA is particularly labile, and hence, these samples provide a sensitive indicator for assessing the IDB's quality-assurance measures. Independent analyses of 104 PBMNC RNA specimens from 26 volunteers revealed that the mean RNA integrity number (RIN) was high (9.

The Infectious Diseases BioBank at King's College London: archiving samples from patients infected with HIV to facilitate translational research.

The King's College London (KCL) Infectious Diseases BioBank opened in 2007 and collects peripheral venous blood (PVB) from individuals infected with pathogens including human immunodeficiency virus (HIV). PVBs are fractionated into plasmas, lymphocytes and DNA and are then frozen. All donations are from subjects who have given 'open consent' so samples can be used for virtually any type of biomedical research.

High risk of human papillomavirus type 16 infections and of development of cervical squamous intraepithelial lesions in systemic lupus erythematosus patients.

Objective: To determine rates of human papillomavirus (HPV) infections, abnormal cervical smears, and squamous intraepithelial lesions (SIL) among women with systemic lupus erythematosus (SLE).

Methods: We investigated 30 women with SLE, 67 with abnormal smears from colposcopy clinics, and 15 community subjects with normal smears. Polymerase chain reaction results for viral DNA and HPV-16 sequencing data were correlated to cytology and colposcopic findings.

Analyses of variant human papillomavirus type-16 E5 proteins for their ability to induce mitogenesis of murine fibroblasts.

Background: Human papillomavirus type 16 (HPV-16) E5 protein co-operates with epidermal growth factor to stimulate mitogenesis of murine fibroblasts. Currently, little is known about which viral amino acids are involved in this process. Using sequence variants of HPV-16 E5 we have investigated their effects upon E5 transcription, cell-cycling and cell-growth of murine fibroblasts.

Detection of HPV transcripts by nested RT-PCR.

Human papillomaviruses (HPVs) are etiologic for the development of cervical cancer and its precursor lesions, cervical intraepithelial neoplasia (CIN). Nearly all cervical carcinomas (CaCx) harbor HPV DNA, but the presence of HPV alone is not indicative of the future development of neoplasia. While both normal and abnormal smears may harbor HPV DNA, the detection of HPV mRNA is associated, although not exclusively, with abnormal cytology.

Identification of HPV variants.

The vast majority of anogenital carcinomas are caused by high-risk human papillomaviruses (HPVs), and among Western nations HPV-16 is usually the most predominant cancer-associated type. As a DNA virus, HPV type 16 has a relatively stable genome that is believed to have co-evolved with its host over the millennia. Nevertheless, among the "wild" populations of HPV-16 that are circulating, a large number of variants have been identified, and these may have considerably different pathogenic potentials.

High-risk mucosal human papillomavirus infections during infancy & childhood.

Human papillomaviruses (HPVs) are small DNA tumour viruses associated with a variety of proliferative diseases. More than 100 types have been identified and can broadly be grouped into cutaneous and mucosal types according to their site of infection, and can be further subdivided into low-risk (LR) and high-risk (HR) types depending upon their association with malignancy. The main route of transmission of HR mucosal HPVs is through sexual contact, although the acquisition of virus cannot be entirely explained by this mode alone.

A human murine mammary tumour virus-like agent is an unconvincing aetiological agent for human breast cancer.

There has recently been renewed interest in both the scientific literature, and in the media, that a human relative (HMLV) of murine mammary tumour virus (MMTV) may be implicated in the aetiology of up to 42% of sporadic cases of human breast cancer. Such reports are potentially of considerable clinical significance, as aside from the small percentage of genetically acquired breast cancers, the cause of sporadic cases of breast cancer is completely unknown. Indeed, convincing proof of an infectious cause for human breast malignancies would permit the development of new preventative measures, treatment modalities and raise the possibility of prophylactic and therapeutic vaccines.

A viral aetiology for breast cancer: time to re-examine the postulate.

Despite decades of research, no aetiologic factor(s) for human breast cancer has been identified and the search for a causal agent has all but been abandoned during the past thirty years. Over 60 years ago, it was demonstrated that breast tumours in mice are caused by an oncornavirus, murine mammary tumour virus (MMTV). Whilst many at that time postulated a similar virus might be the causative agent of human breast cancer, genetic evidence was difficult to obtain primarily because of the occurrence of endogenous human retrovirus (HER) sequences within the human genome that share extensive regions of nucleotide homology with MMTV.

Human murine mammary tumour virus-like agents are genetically distinct from endogenous retroviruses and are not detectable in breast cancer cell lines or biopsies.

It has been reported that a human murine mammary tumour virus (MMTV)-like virus (HMLV), which may be an endogenous human retrovirus (HERV), occurs in the human breast cancer cell lines T47D and MCF-7 and, in 38% of human breast cancer biopsies. As the aetiology of most breast cancers remains unknown, it is important to verify these observations in differing breast cancer populations worldwide. Thus, we sought to determine the genetic relationships between HMLVs, MMTVs, and HERVs, and to investigate the association between HMLVs and breast cancer biopsies from South London, UK.

Buccal exposure to human papillomavirus type 16 is a common yet transitory event of childhood.

High-risk human papillomaviruses, such as type 16 (HPV-16), are established etiological agents for cervical carcinoma. In most cases, this virus is transmitted sexually, though can also be spread from mother to infant at delivery. We have demonstrated previously a high prevalence ( approximately 52%) of HPV-16 DNA in the mouths of prepubertal children, albeit with low levels of transcription [Rice et al.