Nigel James Temperton

Nigel James Temperton
University of Kent | KENT · Medway School of Pharmacy

BSc MSc DLSHTM PhD PGCHE FHEA FRSB
Neutralisation assays for influenza (all subtypes), SARS-CoV-2 + variants and other CoVs.

About

220
Publications
44,187
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Introduction
My R&D focus is on the design, development and deployment of viral pseudotype based neutralisation assays for influenza, coronavirus and other emerging viruses, and receive funding from the MRC, the Bill & Melinda Gates Foundation, Innovate UK, the Wellcome Trust and the Rosetrees Trust. I am Director of the Viral Pseudotype Unit (VPU) within the University of Kent Medway School of Pharmacy, a purpose built, dedicated viral pseudotype R&D laboratory.
Additional affiliations
October 2009 - November 2020
Medway School Of Pharmacy
Position
  • Professor (Full)
January 2003 - September 2009
University College London
January 1998 - December 2000
London School of Hygiene and Tropical Medicine
Position
  • Fellow
Education
September 2010 - September 2011
University of Kent
Field of study
  • Higher Education
January 1993 - January 1998
London School of Hygiene and Tropical Medicine
Field of study
  • Molecular Parasitology
October 1991 - September 1992
London School of Hygiene and Tropical Medicine
Field of study
  • Molecular Parasitology

Publications

Publications (220)
Article
Full-text available
Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10–15 d after the onset of COVID-19 symptoms. However, due to the recent emergence of SARS-CoV-2 in the human population, it is not known how long antibody responses will be maintained or whether they will provide protection from reinfection. Using sequential serum sample...
Article
Full-text available
As of June, 2021, the UK population is only partly vaccinated against COVID-19, with many people having received just one vaccination dose (either BNT162b2 [Pfizer–BioNTech]) or ChAdOx1 nCoV-19 [AZD1222; Oxford–AstraZeneca]). Tracking the spread of SARS-CoV-2 Variants of Concern (VOCs) remains important for understanding the levels of vaccine-induc...
Article
Full-text available
We developed an influenza hemagglutinin (HA) pseudotype library encompassing Influenza A subtypes HA1-18 and Influenza B subtypes (both lineages) to be employed in influenza pseudotype microneutralization (pMN) assays. The pMN is highly sensitive and specific for detecting virus-specific neutralizing antibodies against influenza viruses and can be...
Preprint
Full-text available
RaTG13 is a close relative of SARS-CoV-2, the virus responsible for the Coronavirus Disease 2019 (COVID-19) pandemic, sharing 96% sequence similarity at the genome-wide level. The spike receptor binding domain (RBD) of RaTG13 contains a large number of amino acid substitutions when compared to SARS-CoV-2, likely impacting affinity for the ACE2 rece...
Article
Full-text available
Some filoviruses can be transmitted to humans by zoonotic spillover events from their natural host and filovirus outbreaks have occured with increasing frequency in the last years. The filovirus Lloviu virus (LLOV), was identified in 2002 in Schreiber’s bats ( Miniopterus schreibersii ) in Spain and was subsequently detected in bats in Hungary. Her...
Article
Full-text available
Pattern recognition receptors are crucial for innate anti-viral immunity, including C-type lectin receptors. Two such examples are Lung surfactant protein D (SP-D) and Dendritic cell-specific intercellular adhesion molecules-3 grabbing non-integrin (DC-SIGN) which are soluble and membrane-bound C-type lectin receptors, respectively. SP-D has a cruc...
Article
Full-text available
The virus SARS-CoV-2, responsible for the global COVID-19 pandemic, spread rapidly around the world causing high morbidity and mortality. However, there are four known, endemic seasonal coronaviruses in humans (HCoVs) and whether antibodies for these HCoVs play a role in severity of COVID-19 disease has generated a lot of interest. Of these seasona...
Poster
Full-text available
Lentiviral pseudotype virus library for Influenza A-D.
Article
The Omicron, or Pango lineage B.1.1.529, variant of SARS-CoV-2 carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection from severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple mRNA va...
Article
Full-text available
The Omicron lineage of SARS-CoV-2, first described in November 2021, spread rapidly to become globally dominant and has split into a number of sub-lineages. BA.1 dominated the initial wave but has been replaced by BA.2 in many countries. Recent sequencing from South Africa’s Gauteng region uncovered two new sub-lineages, BA.4 and BA.5 which are tak...
Article
Betacoronavirus SARS-CoV-2, the causative agent of COVID19, is a single stranded positive sense RNA virus. Since its emergence there has been great efforts to identify correlates of protection,which is crucial for vaccine evaluation studies. However, handling SARS-CoV-2 requires BSL-3 containment facilities slowing research efforts. Pseudotype viru...
Article
Full-text available
Equine herpesviruses (EHVs) are enveloped DNA viruses predominantly infecting members of the Equidae family. EHVs primarily cause respiratory disease, however EHV-1 can produce cases of a neurological disease, abortion and neonatal death. Thus, these viruses represent a welfare issue for the equine industry and scientific focus for researchers. EHV...
Article
The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal coronavirus disease (COVID-19) outcomes is that the immune response to the SARS-CoV-2 spike protein is enr...
Preprint
Full-text available
The Omicron lineage of SARS-CoV-2, first described in November 2021, spread rapidly to become globally dominant and has split into a number of sub-lineages. BA.1 dominated the initial wave but has been replaced by BA.2 in many countries. Recent sequencing from South Africa's Gauteng region uncovered two new sub-lineages, BA.4 and BA.5 which are tak...
Article
Full-text available
A major challenge in coronavirus vaccination and treatment is to counteract rapid viral evolution and mutations. Here we demonstrate that CRISPR-Cas13d offers a broad-spectrum antiviral (BSA) to inhibit many SARS-CoV-2 variants and diverse human coronavirus strains with >99% reduction of the viral titer. We show that Cas13d-mediated coronavirus inh...
Preprint
Full-text available
Filoviruses encompass highly pathogenic viruses placing sporadic public health burden on countries affected. Efforts for improved diagnostics and surveillance are needed considering the recent Ebola outbreaks in Africa. The need for high containment facilities can be circumvented by the use of pseudotype viruses (PV), which can be handled in low co...
Article
Full-text available
RaTG13 is a close relative of SARS-CoV-2, the virus responsible for the COVID-19 pandemic, sharing 96% sequence similarity at the genome-wide level. The spike receptor binding domain (RBD) of RaTG13 contains a number of amino acid substitutions when compared to SARS-CoV-2, likely impacting affinity for the ACE2 receptor. Antigenic differences betwe...
Article
Full-text available
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-...
Article
Full-text available
The rise of SARS-CoV-2 variants has made the pursuit to define correlates of protection more troublesome, despite the availability of the World Health Organisation (WHO) International Standard for anti-SARS-CoV-2 Immunoglobulin sera, a key reagent used to standardise laboratory findings into an international unitage. Using pseudotyped virus, we exa...
Article
Full-text available
Background Currently, evaluation of the IgG antibodies specific for the SARS-CoV-2 Spike protein following vaccination is used worldwide to estimate vaccine response. Limited data are available on vaccine-elicited IgM antibodies and their potential implication in immunity to SARS-CoV-2. Methods We performed a longitudinal study to quantify anti-S...
Article
Full-text available
Background Neutralizing antibodies are important for protection against the pandemic SARS-CoV-2 virus, and long-term memory responses determine the risk of re-infection or boosting after vaccination. T-cellular responses are considered important for partial protection against novel variants of concern. Methods A prospective cohort of hospitalized...
Article
Full-text available
Background The COVID-19 pandemic continues to be a worldwide threat and effective antiviral drugs and vaccines are being developed in a joint global effort. However, some elderly and immune-compromised populations are unable to raise an effective immune response against traditional vaccines. Aims We hypothesised that passive immunity engineered by...
Article
Full-text available
The emergence of COVID-19 has emphasised that biological assay data must be analysed quickly to develop safe, effective and timely vaccines/therapeutics. For viruses such as SARS-CoV-2, the primary way of measuring immune correlates of protection is through assays such as the pseudotype microneutralisation (pMN) assay, thanks to its safety and vers...
Article
Full-text available
Background COVID-19 vaccines have demonstrated effectiveness in reducing SARS-CoV-2 mild and severe outcomes. In vaccinated subjects with SARS-CoV-2 history, RBD-specific IgG and pseudovirus neutralization titers were rapidly recalled by a single BTN162b2 vaccine dose to higher levels than those in naïve recipients after the second dose, irrespecti...
Article
Full-text available
Individuals with potential exposure to SARS-CoV-2 do not necessarily develop PCR or antibody positivity, suggesting some may clear sub-clinical infection before seroconversion. T-cells can contribute to the rapid clearance of SARS-CoV-2 and other coronavirus infections1–3. We hypothesised that pre-existing memory T-cell responses, with cross-protec...
Preprint
Full-text available
On the 24th November 2021 the sequence of a new SARS CoV-2 viral isolate spreading rapidly in Southern Africa was announced. Omicron contains a total of 30 substitutions plus deletions and an insertion in Spike, far more than any previously reported variant. The mutations include those previously identified by In-vitro evolution to contribute to hi...
Preprint
Full-text available
On the 24th November 2021 the sequence of a new SARS CoV-2 viral isolate spreading rapidly in Southern Africa was announced. Omicron contains a total of 30 substitutions plus deletions and an insertion in Spike, far more than any previously reported variant. The mutations include those previously identified by In-vitro evolution to contribute to hi...
Article
Full-text available
Precision monitoring of antibody responses during the COVID-19 pandemic is increasingly important during large scale vaccine rollout and rise in prevalence of Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV-2) variants of concern (VOC). Equally important is defining Correlates of Protection (CoP) for SARS-CoV-2 infection and COVID...
Article
Full-text available
This contribution explores in a new statistical perspective the antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 141 coronavirus disease 2019 (COVID-19) patients exhibiting a broad range of clinical manifestations. This cohort accurately reflects the characteristics of the first wave of the SARS-CoV-2 pandemic i...
Article
Full-text available
This protocol details a rapid and reliable method for the production and titration of high-titer viral pseudotype particles with the SARS-CoV-2 spike protein (and D614G variant) on a lentiviral vector core, and use for neutralization assays in target cells expressing ACE2 and TMPRSS2. It additionally provides detailed instruction on substituting in...
Article
Full-text available
Highly pathogenic H5N1 avian influenza viruses cause devastating outbreaks in farmed poultry with serious consequences for animal welfare and economic losses. Zoonotic infection of humans through close contact with H5N1 infected birds is often severe and fatal. England experienced an outbreak of H5N1 in turkeys in 1991 that led to thousands of farm...
Article
Full-text available
Alpha-B.1.1.7, Beta-B.1.351, Gamma-P.1 and Delta-B.1.617.2 variants of SARS-CoV-2 express multiple mutations in the spike protein (S). These may alter the antigenic structure of S, causing escape from natural or vaccine-induced immunity. Beta is particularly difficult to neutralize using serum induced by early pandemic SARS-CoV-2 strains and is mos...
Preprint
Of the coronaviruses that have caused zoonotic spill overs in past two decades, the diverse group of beta-coronaviruses (β-CoVs) represent the greatest threats. Towards achieving broad vaccine protection from these viruses, vaccines composed of multiple antigens, each capable of eliciting broad neutralising responses across a subgroup will be requi...
Preprint
Full-text available
The virus SARS-CoV-2, responsible for the global COVID-19 pandemic, spread rapidly around the world causing high morbidity and mortality because humans have no pre-existing immunity. However, there are four known, endemic seasonal coronaviruses in humans (HCoVs) and whether antibodies for these HCoVs play a role in severity of COVID-19 disease has...
Preprint
Full-text available
To better understand how inhibition of the influenza neuraminidase (NA) protein contributes to protection against influenza, and to investigate its breadth and cross-neutralizing activity, we have produced lentiviral vectors pseudotyped with an avian H11 hemagglutinin (HA) and the NA (N1- N9) of all influenza A and (B/Victoria and B/Yamagata) influ...
Preprint
Full-text available
Background The rise of SARS-CoV-2 variants has made the pursuit to define correlates of protection more troublesome, despite the availability of the World Health Organisation (WHO) International Standard for anti-SARS-CoV-2 Immunoglobulin sera, a key reagent used to standardise laboratory findings into an international unitage. Methods Using pseud...
Article
Full-text available
The novel coronavirus SARS-CoV-2 is the seventh identified human coronavirus. Understanding the extent of pre-existing immunity induced by seropositivity to endemic seasonal coronaviruses and the impact of cross-reactivity on COVID-19 disease progression remains a key research question in immunity to SARS-CoV-2 and the immunopathology of COVID-2019...
Preprint
Full-text available
Filoviruses are prime examples of emerging human pathogens that are transmitted to humans by zoonotic spillover events. Since their initial discovery, filovirus outbreaks have occured with increasing frequency and intensity. There is an urgent need to better understand their enzootic ecology and pathogenic potential, given recent zoonotic virus spi...
Article
Full-text available
We demonstrated pre-existing cross-reactive anti-SARS-CoV-2 antibodies in pre-pandemic serum samples from children and young adults, which were likely derived from previous infection with common endemic -coronaviruses. Promoting this cross-reactive immunity may be an effective strategy against SARS-COV-2 and future novel coronaviruses.
Article
Full-text available
Background: A notable feature of COVID-19 is that children are less susceptible to severe disease. Children are known to experience more infections with endemic human coronaviruses (HCoVs) compared to adults. Little is known whether HCoV infections lead to cross-reactive anti-SARS-CoV-2 antibodies. Methods: We investigated the presence of cross-...
Preprint
Full-text available
Approximately 75% of the UK population has received only one dose of a 2-dose COVID-19 vaccine regime in the face of circulating SARS-CoV-2 Variants of Concern (VOCs). We aimed to determine the levels of vaccine-induced neutralising antibodies to SARS-CoV-2 variants B.1.1.7, B.1.351 and P.1. To do so, we undertook a single-centre cross-sectional st...
Preprint
Full-text available
The novel coronavirus SARS-CoV-2 is the seventh identified human coronavirus. Understanding the extent of pre-existing immunity induced by seropositivity to endemic seasonal coronaviruses and the impact of cross-reactivity on COVID-19 disease progression remains a key research question in immunity to SARS-CoV-2 and the immunopathology of COVID-2019...
Article
Full-text available
SARS-CoV-2 has undergone progressive change with variants conferring advantage rapidly becoming dominant lineages e.g. B.1.617. With apparent increased transmissibility variant B.1.617.2 has contributed to the current wave of infection ravaging the Indian subcontinent and has been designated a variant of concern in the UK. Here we study the ability...
Preprint
Full-text available
Background The rise of SARS-CoV-2 variants has made the pursuit to define correlates of protection more troublesome, despite the availability of the World Health Organisation (WHO) International Standard for anti-SARS-CoV-2 Immunoglobulin sera, a key reagent used to standardise laboratory findings into an international unitage. Methods Using pseud...
Preprint
Full-text available
Precision monitoring of antibody responses during the COVID-19 pandemic is increasingly important during large scale vaccine rollout and rise in prevalence of Severe Acute Respiratory Syndrome- related Coronavirus-2 (SARS-CoV-2) variants of concern (VOC). Equally important is defining Correlates of Protection (CoP) for SARS-CoV-2 infection and COVI...
Preprint
Full-text available
We have developed an influenza hemagglutinin (HA) pseudotype library encompassing Influenza A subtypes HA1-18, and Influenza B subtypes (both lineages) to be employed in influenza pseudotype microneutralization (pMN) assays. The pMN is highly sensitive and specific for de-tecting virus-specific neutralizing antibodies against influenza viruses and...
Preprint
Full-text available
It is unclear whether prior endemic coronavirus infections affect COVID-19 severity. Here, we show that in cases of fatal COVID-19, antibody responses to the SARS-COV-2 spike are directed against epitopes shared with endemic beta-coronaviruses in the S2 subunit of the SARS-CoV-2 spike protein. This immune response is associated with the compromised...
Article
Full-text available
SARS-CoV-2 transmission is uncontrolled in many parts of the world, compounded in some areas by higher transmission potential of the B1.1.7 variant¹ now reported in 94 countries. It is unclear whether responses to SARS-CoV-2 vaccines based on the prototypic strain will be impacted by mutations found in B.1.1.7. Here we assessed immune responses fol...
Article
Full-text available
Influenza B viruses (IBV) cause respiratory disease epidemics in humans and are therefore components of seasonal influenza vaccines. Serological methods are employed to evaluate vaccine immunogenicity prior to licensure. However, classical methods to assess influenza vaccine immunogenicity such as the hemagglutination inhibition assay (HI) and the...
Article
Full-text available
SARS-CoV-2 vaccine rollout has coincided with the spread of variants of concern. We investigated if single dose vaccination, with or without prior infection, confers cross protective immunity to variants. We analyzed T and B cell responses after first dose vaccination with the Pfizer/BioNTech mRNA vaccine BNT162b2 in healthcare workers (HCW) follow...
Article
Full-text available
SARS-CoV-2 virus was first detected in late 2019 and circulated globally, causing COVID-19, which is characterised by sub-clinical to severe disease in humans. Here, we investigate the serological antibody responses to SARS-CoV-2 infection during acute and convalescent infection using a cohort of (i) COVID-19 patients admitted to hospital, (ii) hea...
Article
Full-text available
SARS-CoV-2 virus was first detected in late 2019 and circulated globally, causing COVID19, which is characterised by sub-clinical to severe disease in humans. Here, we investigate the serological antibody responses to SARS-CoV-2 infection during acute and convalescent infection using a cohort of (i) COVID-19 patients admitted to hospital, (ii) heal...