Holly E. Humphries
A5026408068- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Bacterial Infections and Vaccines
- Pneumonia and Respiratory Infections
- Animal Virus Infections Studies
- Immunotherapy and Immune Responses
- Respiratory viral infections research
- Neonatal and Maternal Infections
- Immune Response and Inflammation
- Virus-based gene therapy research
- Monoclonal and Polyclonal Antibodies Research
- Escherichia coli research studies
- Complement system in diseases
- COVID-19 epidemiological studies
- Bacteriophages and microbial interactions
- Infection Control and Ventilation
- Viral gastroenteritis research and epidemiology
- Influenza Virus Research Studies
- Neonatal Respiratory Health Research
- Immune responses and vaccinations
- Streptococcal Infections and Treatments
- COVID-19 diagnosis using AI
- Infant Nutrition and Health
- RNA and protein synthesis mechanisms
- Amoebic Infections and Treatments
Public Health England
2015-2023
University of Southampton
2002-2006
Southampton General Hospital
2002-2006
University of Manchester
2002
Abstract The global supply of COVID-19 vaccines remains limited. An understanding the immune response that is predictive protection could facilitate rapid licensure new vaccines. Data from a randomized efficacy trial ChAdOx1 nCoV-19 (AZD1222) vaccine in United Kingdom was analyzed to determine antibody levels associated with against SARS-CoV-2. Binding and neutralizing antibodies at 28 days after second dose were measured infected noninfected recipients. Higher all markers correlated reduced...
SARS-CoV-2 has caused over 2 million deaths in little a year. Vaccines are being deployed at scale, aiming to generate responses against the virus spike. The scale of pandemic and error-prone replication is leading appearance mutant viruses potentially escape from antibody responses. Variant B.1.1.7, now dominant UK, with increased transmission, harbors 9 amino acid changes spike, including N501Y ACE2 interacting surface. We examine ability B.1.1.7 evade elicited by natural infection or...
There is a vital need for authentic COVID-19 animal models to enable the pre-clinical evaluation of candidate vaccines and therapeutics. Here we report dose titration study SARS-CoV-2 in ferret model. After high (5 × 106 pfu) medium 104 virus delivered, intranasally, viral RNA shedding upper respiratory tract (URT) observed 6/6 animals, however, only 1/6 ferrets show similar signs after low 102 challenge. Following sequential culls pathological mild multifocal bronchopneumonia approximately...
Abstract Background Although 6 COVID-19 vaccines have been approved by the World Health Organisation as of 16 th June 2021, global supply remains limited. An understanding immune response associated with protection could facilitate rapid licensure new vaccines. Methods Data from a randomised efficacy trial ChAdOx1 nCoV-19 (AZD1222) vaccine in UK was analysed to determine antibody levels against SARS-CoV-2. Anti-spike and anti-RBD IgG multiplex immunoassay, pseudovirus live neutralising at 28...
A novel coronavirus, SARS-CoV-2, has been identified as the causative agent of current COVID-19 pandemic. Animal models, and in particular non-human primates, are essential to understand pathogenesis emerging diseases assess safety efficacy vaccines therapeutics. Here, we show that SARS-CoV-2 replicates upper lower respiratory tract causes pulmonary lesions both rhesus cynomolgus macaques. Immune responses against also similar species equivalent those reported milder infections convalescent...
Abstract The ongoing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic necessitates the fast development of vaccines to meet a worldwide need. mRNA-based are most promising technology for rapid and safe SARS-CoV-2 vaccine production. We have designed CVnCoV, lipid-nanoparticle (LNP) encapsulated, sequence optimised that encodes full length, pre-fusion stabilised Spike protein. Unlike other approaches, CVnCoV exclusively consists non-chemically modified nucleotides can be...
Abstract In December 2019 an outbreak of coronavirus disease (COVID-19) emerged in Wuhan, China. The causative agent was subsequently identified and named severe acute respiratory syndrome 2 (SARS-CoV-2) which rapidly spread worldwide causing a pandemic. Currently there are no licensed vaccines or therapeutics available against SARS-CoV-2 but numerous candidate development repurposed drugs being tested the clinic. There is vital need for authentic COVID-19 animal models to further our...
The tuberculosis vaccine, Bacille Calmette-Guerin (BCG), also affords protection against non-tuberculous diseases attributable to heterologous immune mechanisms such as trained innate immunity, activation of non-conventional T-cells, and cross-reactive adaptive immunity. Aerosol vaccine delivery can target responses toward the primary site infection for a respiratory pathogen. Therefore, we hypothesised that aerosol BCG would enhance cross-protective action severe acute syndrome...
ABSTRACT Current experimental vaccines against serogroup B Neisseria meningitidis are based on meningococcal outer membrane (OM) proteins present in vesicles (OMV) which toxic lipopolysaccharide is depleted by detergent extraction. Knowledge of the composition OM and OMV essential for developing new defined antigens. In current study, sodium dodecyl sulfate-polyacrylamide gel electrophoresis nanocapillary liquid chromatography-tandem mass spectrometry were used to investigate proteomes from...
There is an urgent requirement for safe and effective vaccines to prevent COVID-19. A concern the development of new viral potential induce vaccine-enhanced disease (VED). This was reported in several preclinical studies with both SARS-CoV-1 MERS but has not been SARS-CoV-2 vaccines. We have used ferrets rhesus macaques challenged assess VED animals vaccinated formaldehyde-inactivated (FIV) formulated Alhydrogel, compared a negative control vaccine. showed no evidence enhanced or given FIV...
Abstract The trajectory of immune responses following the primary dose series determines decline in vaccine effectiveness over time. Here we report on maintenance during year a two-dose schedule ChAdOx1 nCoV-19/AZD1222, absence infection, and also explore decay antibody after infection. Total spike-specific IgG titres were lower with two low doses nCoV-19 vaccines (two doses) (P = 0.0006) than 2 standard (the approved dose) or followed by regimens. Longer intervals between first second...
The interactions of Neisseria meningitidis with cells the meninges are critical to progression acute, compartmentalized intracranial inflammatory response that is characteristic meningococcal meningitis. An important virulence mechanism bacteria ability shed outer membrane (OM) blebs containing lipopolysaccharide (LPS), which has been assumed be major pro-inflammatory molecule produced during Comparison cytokine induction by human meningeal following infection wild-type meningococci,...
Abstract Vaccines against SARS-CoV-2 are urgently required, but early development of vaccines SARS-CoV-1 resulted in enhanced disease after vaccination. Careful assessment this phenomena is warranted for vaccine SARS CoV-2. Here we report detailed immune profiling ChAdOx1 nCoV-19 (AZD1222) and subsequent high dose challenge two animal models mediated disease. We demonstrate rhesus macaques the lung pathology caused by pneumonia reduced prior vaccination with which induced neutralising...
Safe and effective vaccines will provide essential medical countermeasures to tackle the COVID-19 pandemic. Here, we assessed safety, immunogenicity efficacy of intradermal delivery INO-4800, a synthetic DNA vaccine candidate encoding SARS-CoV-2 spike protein in rhesus macaque model. Single 2 dose vaccination regimens were evaluated. Vaccination induced both binding neutralizing antibodies, along with IFN-γ-producing T cells against SARS-CoV-2. Upon administration high viral (5 × 10
Vertical transmission of Group B Streptococcus (GBS) is a prerequisite for early-onset disease and consequence maternal GBS colonization. Disease protection associated with maternally-derived anti-GBS antibody. Using novel antibody-mediated C3b/iC3b deposition flow cytometry assay which correlates opsonic killing we developed model to assess the impact functional antibody on infant colonization from birth day 60–89 life. Rectovaginal swabs cord blood (birth) nasopharyngeal/rectal (birth, 6...
Background: Group B Streptococcus is a major cause of mortality and morbidity in infants associated with transmission from colonised mother at birth via infected breastmilk. Although maternal/infant colonisation (GBS) common, the majority exposed to GBS remain unaffected. The association between breastmilk immune factors infant disease prevention has not been elucidated. Objectives: We have investigated SIgA cytokines clearance. Methods: Mother/infant was determined prospective cohort 750...
The major porin proteins present in the outer membrane of Neisseria meningitidis, causative agent life-threatening meningitis and septicaemia, are believed to have potent immunostimulatory effects. In this study, interactions between human monocyte-derived dendritic cells (mo-DC) PorA were investigated, order reveal role protein promoting innate adaptive immune responses. Recombinant (r)PorA induced mo-DC maturation, as reflected by reduced receptor-mediated endocytosis, increased production...
The rationale for the present study was to determine how different species of bacteria interact with cells human meninges in order gain information that would have broad relevance understanding aspects innate immune response brain. Neisseria lactamica is an occasional cause meningitis humans, and this we investigated vitro interactions between N. derived from leptomeninges comparison closely related organism meningitidis, a major worldwide. adhered specifically meningioma cells, but levels...
The human nasopharynx contains a stable microbial ecosystem of commensal and potentially pathogenic bacteria, which can elicit protective primary secondary immune responses. Experimental intranasal infection adults with the Neisseria lactamica produced safe, sustained pharyngeal colonization. This has potential utility as vehicle for release antigen to mucosa, but commensals in general are thought be immunologically tolerated. Here, we show that engineered N. lactamica, chromosomally...
LicA encodes the enzyme phosphorylcholine kinase which catalyses incorporation of (ChoP) into H. influenzae LPS. Expression this gene is subject to phase variation, resulting in spontaneous loss, or gain (ChoP)-decorated LPS structures. To investigate role phenomenon pathogenesis invasive disease an mutant was constructed lacked ability vary licA. This achieved by introducing in-frame deletion 5′-CAAT-3′ repeats licA using polymerase chain reaction. The resultant mutant, licAΔ5′-CAAT-3′,...
The correlate of protection for the licensure meningococcal vaccines is serum bactericidal activity. However, evidence indicates that a complex situation and other mechanisms, such as antibody-mediated, complement-dependent opsonophagocytosis (OP), may play role in should be investigated order to understand immunity this disease. In study, high-throughput flow cytometric opsonophagocytic assay (OPA) was optimized. measures presence killed fluorescently labeled Neisseria meningitidis within...