Christopher Conlon

University of Oxford | OX · Nuffield Department of Clinical Medicine

Antiretroviral treatment (ART) initiation during the early stages of HIV-1 infection is associated with a higher probability of maintaining drug-free viral control during subsequent treatment interruptions, for reasons that remain unclear. Using samples from a randomized-controlled human clinical trial evaluating therapeutic HIV-1 vaccines, we here...

T cell responses to SARS-CoV-2 following infection and vaccination are less characterised than antibody responses, due to a more complex experimental pathway.We measured T cell responses in 108 healthcare workers (HCWs) using the commercialised Oxford Immunotec T-SPOT Discovery SARS-CoV-2 assay service (OI T-SPOT) and the PITCH ELISpot protocol est...

Highly transmissible Omicron variants of SARS-CoV-2 currently dominate globally. Here, we compare neutralization of Omicron BA.1, BA.1.1 and BA.2. BA.2 RBD has slightly higher ACE2 affinity than BA.1 and slightly reduced neutralization by vaccine serum, possibly associated with its increased transmissibility. Neutralization differences between sub-...

Background T cell responses to SARS-CoV-2 following infection and vaccination are less characterised than antibody responses, due to a more complex experimental pathway. Methods We measured T cell responses in 108 healthcare workers (HCWs) in an observational cohort study, using the commercialised Oxford Immunotec T-SPOT Discovery SARS-CoV-2 assay...

Background Previous infection with SARS-CoV-2 affects the immune response to the first dose of the SARS-CoV-2 vaccine. We aimed to compare SARS-CoV-2-specific T-cell and antibody responses in health-care workers with and without previous SARS-CoV-2 infection following a single dose of the BNT162b2 (tozinameran; Pfizer–BioNTech) mRNA vaccine. Method...

Background: Previous infection with SARS-CoV-2 affects the immune response to the first dose of the SARS-CoV-2 vaccine. We aimed to compare SARS-CoV-2-specific T-cell and antibody responses in health-care workers with and without previous SARS-CoV-2 infection following a single dose of the BNT162b2 (tozinameran; Pfizer-BioNTech) mRNA vaccine. Met...

Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the UK to accelerate population coverage with a single dose. At this time, trial data was lacking, and we addressed this in a study of UK healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) va...

The extent to which immune responses to natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and immunization with vaccines protect against variants of concern (VOC) is of increasing importance. Accordingly, here we analyse antibodies and T cells of a recently vaccinated, UK cohort, alongside those recovering from nat...

Background: Natural and vaccine-induced immunity will play a key role in controlling the SARS-CoV-2 pandemic. SARS-CoV-2 variants have the potential to evade natural and vaccine-induced immunity. Methods: In a longitudinal cohort study of healthcare workers (HCWs) in Oxfordshire, UK, we investigated the protection from symptomatic and asymptomat...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is normally controlled by effective host immunity including innate, humoral and cellular responses. However, the trajectories and correlates of acquired immunity, and the capacity of memory responses months after infection to neutralise variants of concern - which has important...

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete understanding of potentially druggable immune mediators of disease. To advance this, we present a comprehensive multi-omic blood atlas in patients with varying COVID-19 severity and compare with influenza, sepsis and healthy volunteers. We identify immune sig...

p>More than 190 vaccines are currently in development to prevent infection by the novel severe acute respiratory syndrome coronavirus 2. Animal studies suggest that while neutralizing antibodies against the viral spike protein may correlate with protection, additional antibody functions may also be important in preventing infection. Previously, we...

Persistence of HIV through integration into host DNA in CD4⁺ T cells presents a major barrier to virus eradication. Viral integration may be curtailed when CD8⁺ T cells are triggered to kill infected CD4⁺ T cells through recognition of histocompatibility leukocyte antigen (HLA) class I-bound peptides derived from incoming virions. However, this has...

The immunogenicity of the candidate tuberculosis (TB) vaccine MVA85A may be enhanced by aerosol delivery. Intradermal administration was shown to be safe in adults with latent TB infection (LTBI), but data are lacking for aerosol-delivered candidate TB vaccines in this population. We carried out a Phase I trial to evaluate the safety and immunogeni...

Background: Following a single dose of BNT162b2 mRNA vaccine, higher antibody titres are observed following prior SARS-CoV-2 infection than in infection-naive individuals, but T-cell responses are less well defined. Methods: We sampled healthcare workers (HCWs) enrolled in the UK PITCH study, before and after BNT162b2 mRNA vaccination. We measured...

Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity to other coronaviruses. Here we show a range of T cell assays that differentially capture immune function to characterise SARS-CoV-2 responses. Strong ex vivo ELISpot and proliferation resp...

Serological detection of antibodies to SARS-CoV-2 is essential for establishing rates of seroconversion in populations, and for seeking evidence for a level of antibody that may be protective against COVID-19 disease. Several high-performance commercial tests have been described, but these require centralised laboratory facilities that are comparat...

Background Natural and vaccine-induced immunity will play a key role in controlling the SARS-CoV-2 pandemic. SARS-CoV-2 variants have the potential to evade natural and vaccine-induced immunity. Methods In a longitudinal cohort study of healthcare workers (HCWs) in Oxfordshire, UK, we investigated the protection from symptomatic and asymptomatic PC...

Background The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4–12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first d...

Background Thresholds for SARS-CoV-2 antibody assays have typically been determined using samples from symptomatic, often hospitalised, patients. In this setting the sensitivity and specificity of the best performing assays can both exceed 98%. However, antibody assay performance following mild infection is less clear. Methods We assessed quantita...

Both natural infection with SARS-CoV-2 and immunization with a number of vaccines induce protective immunity. However, the ability of such immune responses to recognize and therefore protect against emerging variants is a matter of increasing importance. Such variants of concern (VOC) include isolates of lineage B1.1.7, first identified in the UK,...

Both natural infection with SARS-CoV-2 and immunization with vaccines induce protective immunity. However, the extent to which such immune responses protect against emerging variants is of increasing importance. Such variants of concern (VOC) include isolates of lineage B.1.1.7, first identified in the UK, and B.1.351, first identified in South Afr...

Background SARS-CoV-2 IgG antibody measurements can be used to estimate the proportion of a population exposed or infected and may be informative about the risk of future infection. Previous estimates of the duration of antibody responses vary. Methods We present 6 months of data from a longitudinal seroprevalence study of 3276 UK healthcare worke...

Background The relationship between the presence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the risk of subsequent reinfection remains unclear. Methods We investigated the incidence of SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) in seropositive and seronegative health care workers attend...

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes dat...

Background and purpose More and more reports had observed the thrombosis in severe COVID-19 cases. The aim of this study was to evaluate the incidence of thromboembolism in mild/ moderate COVID-19. All of the patients had normal coagulation tests and had no overt thrombotic complications. It is important to screen the thrombotic status in mild/mode...

Older adults are at higher risk of severe disease and death if they develop COVID-19 and are therefore a priority for immunisation should an efficacious vaccine be developed. Immunogenicity of vaccines is often poorer in older adults as a result of immunosenescence. We recently reported the immunogenicity of a novel viral vectored vaccine, ChAdOx1...

Background It is critical to understand whether infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) protects from subsequent reinfection. Methods We investigated the incidence of SARS-CoV-2 PCR-positive results in seropositive and seronegative healthcare workers (HCWs) attending asymptomatic and symptomatic staff testing at...

Background SARS-CoV-2 IgG antibody measurements can be used to estimate the proportion of a population exposed or infected and may be informative about the risk of future infection. Previous estimates of the duration of antibody responses vary. Methods We present 6 months of data from a longitudinal seroprevalence study of 3217 UK healthcare worke...

The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-γ-based assays with peptides spann...

Background Older adults (aged ≥70 years) are at increased risk of severe disease and death if they develop COVID-19 and are therefore a priority for immunisation should an efficacious vaccine be developed. Immunogenicity of vaccines is often worse in older adults as a result of immunosenescence. We have reported the immunogenicity of a novel chimpa...

A major issue in identification of protective T cell responses against SARS-CoV-2 lies in distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity generated by exposure to other coronaviruses. We characterised SARS-CoV-2 T cell immune responses in 168 PCR-confirmed SARS-CoV-2 infected subjects and 118 seronegative subj...

We conducted voluntary Covid-19 testing programmes for symptomatic and asymptomatic staff at a UK teaching hospital using naso-/oro-pharyngeal PCR testing and immunoassays for IgG antibodies. 1128/10,034(11.2%) staff had evidence of Covid-19 at some time. Using questionnaire data provided on potential risk-factors, staff with a confirmed household...

We conducted voluntary Covid-19 testing programmes for symptomatic and asymptomatic staff at a UK teaching hospital using naso-/oro-pharyngeal PCR testing and immunoassays for IgG antibodies. 1128/10,034 (11.2%) staff had evidence of Covid-19 at some time. Using questionnaire data provided on potential risk-factors, staff with a confirmed household...

We conducted voluntary Covid-19 testing programmes for symptomatic and asymptomatic staff at a UK teaching hospital using naso-/oro-pharyngeal PCR testing and immunoassays for IgG antibodies. 1128/10,034 (11.2%) staff had evidence of Covid-19 at some time. Using questionnaire data provided on potential risk-factors, staff with a confirmed household...

Thresholds for SARS-CoV-2 antibody assays have typically been determined using samples from symptomatic, often hospitalised, patients. Assay performance following mild/asymptomatic infection is unclear. We assessed IgG responses in asymptomatic healthcare workers with a high pre-test probability of Covid-19, e.g. 807/9292(8.9%) reported loss of sme...

Background The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2. Methods We did a phase 1/2, single-blind, randomised controlled trial in five t...

Background Personal protective equipment (PPE) and social distancing are key measures designed to mitigate the risk of occupational SARS-CoV-2 infection in hospitals. Why healthcare workers nevertheless remain at increased risk is uncertain. Methods We conducted voluntary Covid-19 testing programmes for symptomatic and asymptomatic staff at a large...

Background Since its discovery, SARS-CoV-2 has been spread throughout China before becoming a global pandemic. In Beijing, family clusters are the main mode of human-human transmission accounting for 57.6% of the total confirmed cases. Method We present the epidemiological and clinical features of the clusters of three large and one small families...

The Oxford Textbook of Medicine is published online and has been regularly updated for many years, but the production of a new and very substantially updated edition provides a moment when it is natural and proper to reflect on what has changed in Medicine—and what has not—in recent years. The sixth edition of the textbook considers exactly what mo...

Molluscum contagiosum is caused by a Molluscipox DNA virus which infects keratinocytes of the epidermal stratum spinosum, producing distinctive small umbilicated papules on the skin. Its genome encodes a variety of proteins that suppress the host’s immune response. In children it is spread by skin contact, producing few or many lesions, while in se...

Tourists, business people, pilgrims, and visitors to friends and relatives are making increasing numbers of trips to tropical and developing parts of the world, where the risk and range of infectious and environmental diseases and injuries may be much higher than in Western countries. The aim of travel and expedition medicine is to reduce risk thro...

Since its discovery in 1983, the human immunodeficiency virus (HIV) has been associated with a global pandemic that has affected more than 78 million people and caused more than 39 million deaths. Globally, 36.9 million (34.3–41.4 million) people were living with HIV at the end of 2013. An estimated 0.8% of adults aged 15–49 years worldwide are liv...

A novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2), first appeared in the city of Wuhan in Central China in December 2019. Initial cases appeared to be centred on a so-called wet market, but the outbreak spread rapidly. The World Health Organisation (WHO) declared a Pandemic Health Emergency of International Concern...

The Oxford Textbook of Medicine is published online and has been regularly updated for many years, but the production of a new and very substantially updated edition provides a moment when it is natural and proper to reflect on what has changed in Medicine—and what has not—in recent years. The sixth edition of the textbook considers exactly what mo...

Background: Antiretroviral therapy (ART) cannot cure HIV infection because of a persistent reservoir of latently infected cells. Approaches that force HIV transcription from these cells, making them susceptible to killing-termed kick and kill regimens-have been explored as a strategy towards an HIV cure. RIVER is the first randomised trial to dete...

Enrichment of CD103+ tumor-infiltrating T lymphocytes (TILs) is associated with improved outcomes in patients. However, the characteristics of human CD103+ cytotoxic CD8+ T cells (CTLs) and their role in tumor control remains unclear. We investigated the features and antitumor mechanisms of CD103+ CTLs by assessing T-cell receptor (TCR)-matched CD1...

Background: Cancer patients often display dysfunctional antitumor T-cell responses. Because noteworthy benefits of immune checkpoint pathway blockade, such as programmed cell death protein 1 (PD-1) inhibitors, have been achieved in multiple advanced cancers, the next critical question is which mono-blockade or combinatorial blockade regimens may re...

Immunotherapy treatments with anti-PD-1 boost recovery in less than 30% of treated cancer patients, indicating the complexity of the tumor microenvironment. Expression of HLA-E is linked to poor clinical outcomes in mice and human patients. However, the contributions to immune evasion of HLA-E, a ligand for the inhibitory CD94/NKG2A receptor, when...

Background: The clinical utility of interferon-γ release assays (IGRAs) for diagnosis of active tuberculosis is unclear, although they are commonly used in countries with a low incidence of tuberculosis. We aimed to resolve this clinical uncertainty by determining the accuracy and utility of commercially available and second-generation IGRAs in th...

Hepatitis B (HBV), hepatitis C (HCV), and human immunodeficiency virus (HIV) infections have particular implications for fitness for work. These include the impact of symptoms and disease, the transmissibility of infection in the course of specific work activities, and, in the case of HIV, vulnerability to other infections arising from immune defic...

Background The role of interferon-gamma release assays (IGRAs) in diagnosis of active tuberculosis (TB) is unclear, yet they are commonly used in low-TB-incidence countries. This study sought to resolve this clinical uncertainty by determining the diagnostic accuracy and role of current and second-generation IGRAs in the diagnostic assessment of su...

Although fungal infections of bones and joints are rare, the increasing incidence of invasive fungal disease, along with an increased population of immunosuppressed patients and individuals with multiple comorbidities, means that these infections are also increasing. The most common organisms are Candida and Aspergillus species, although the endemi...

https://oxfordmedicine.com/view/10.1093/med/9780198755388.001.0001/med-9780198755388

Aim: To perform a systematic review, meta-analysis and Delphi exercise to evaluate diagnostic yield of combined 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography and computed tomography (FDG-PET/CT) in fever of unknown origin (FUO). Materials and methods: Four databases were searched for studies of FDG-PET/CT in FUO 1/1/2000-...

A 54-year-old black African woman, 22 years human immunodeficiency virus (HIV)-positive, presented with an acute coronary syndrome. She was taking two nucleoside reverse transcriptase inhibitors and two protease inhibitors. Viral load and CD4 count were stable. Angiography revealed a right coronary artery lesion, which was treated with everolimus e...

Learning point for clinicians Infection control practices in clinical areas are designed to prevent Mycobacterium tuberculosis being transmitted via airway emitted droplet nuclei.1 According to this paradigm pulmonary smear positive disease is considered more infectious than smear negative disease,2 whereas extra-pulmonary disease, which should no...

Japanese encephalitis (JE) virus (JEV) is an important cause of encephalitis in children of South and Southeast Asia. However, the majority of individuals exposed to JEV only develop mild symptoms associated with long-lasting adaptive immunity. The related flavivirus dengue virus (DENV) cocirculates in many JEV-endemic areas, and clinical data sugg...

Patients born outside the UK have contributed to a 20% rise in the UK's tuberculosis incidence since 2000, but their effect on domestic transmission is not known. Here we use whole-genome sequencing to investigate the epidemiology of tuberculosis transmission in an unselected population over 6 years. We identified all residents with Oxfordshire pos...

Previous studies have suggested that there may be an association between some immune-mediated diseases and risk of tuberculosis (TB). We analyzed a database of linked statistical records of hospital admissions and death certificates for the whole of England (1999 to 2011), and a similar database (the Oxford Record Linkage Study (ORLS)) for a region...

Despite significant advances in the treatment of HIV infection and dramatic increases in disease-free survival, there has not been a corresponding increase in employment for those infected with HIV. It is likely that drug side effects, psychological barriers, and continuing (but lessening) prejudice among employers contribute. Occupational physicia...

A 60-year-old man presented with an acute, pruritic, erythematous rash associated with marked hypereosinophilia (2.34×10(9)/l (0.04-0.40)). There was eosinophilic infiltration on hepatic, bone marrow and lymph node biopsies, with multiple lung nodules and mild splenomegaly. However, extensive investigation excluded parasitic or bacterial causes, sp...

A 45-year-old man presented to hospital with shortness of breath. Although he had been feeling increasingly tired in the preceding months he did not attend his own doctor until his walking distance was reduced to 50 yards. At this point his full blood count was checked and his haemoglobin was 3.4 g/dl. He was a smoker and initially had a raised bod...