Miles P Davenport

Miles P Davenport
UNSW Sydney | UNSW · Kirby Institute

MB BS D.Phil

About

379
Publications
31,246
Reads
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12,381
Citations
Introduction
Professor Davenport is an MD-PhD (MB BS, DPhil) who leads a team of mathematicians to understand host control of infection.
Additional affiliations
May 2020 - present
eLife
Position
  • Editor
July 2019 - May 2020
eLife
Position
  • Editor
January 2019 - present
Immunology and Cell Biology
Position
  • Editor
Education
January 1993 - November 1995
University of Oxford
Field of study
  • Clinical Medicine (Immunology)
January 1990 - December 1990
The University of Sydney
Field of study
  • Immunology
January 1987 - December 1996
The University of Sydney
Field of study
  • Medicine

Publications

Publications (379)
Article
Full-text available
There is currently a need for proxy measures of the HIV rebound competent reservoir (RCR) that can predict viral rebound after combined antiretroviral treatment (cART) interruption. In this study, macaques infected with a barcoded SIVmac239 virus received cART beginning between 4- and 27-days post-infection, leading to the establishment of differen...
Article
We are just beginning to understand the diversity of the peripheral T cell compartment, which arises from the specialization of different T cell subsets and the plasticity of individual naive T cells to adopt different fates. Although the progeny of a single T cell can differentiate into many phenotypes following infection, individual T cells are b...
Article
Full-text available
Predictive models of immune protection from COVID-19 are urgently needed to identify correlates of protection to assist in the future deployment of vaccines. To address this, we analyzed the relationship between in vitro neutralization levels and the observed protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection usi...
Article
Full-text available
Background Several SARS-CoV-2 variants of concern have been identified that partly escape serum neutralisation elicited by current vaccines. Studies have also shown that vaccines demonstrate reduced protection against symptomatic infection with SARS-CoV-2 variants. We explored whether in-vitro neutralisation titres remain predictive of vaccine prot...
Preprint
Full-text available
Vaccination against SARS-CoV-2 results in protection from acquisition of infection as well as improved clinical outcomes even if infection occurs, likely reflecting a combination of residual vaccine-elicited immunity and the recall of immunological memory. Here, we define the early kinetics of spike-specific humoral and T cell immunity after vaccin...
Preprint
Full-text available
As a result of the emergence and circulation of antigenically distinct SARS-CoV-2 variants, a number of variant-modified COVID-19 vaccines have been developed. Here we perform a meta-analysis of the available data on neutralisation titres from clinical studies comparing booster vaccination with either the current ancestral-based vaccines or variant...
Article
Full-text available
The rate at which parasitemia declines in a host after treatment with an antimalarial drug is a major metric for assessment of antimalarial drug activity in preclinical models and in early clinical trials. However, this metric does not distinguish between viable and nonviable parasites. Thus, enumeration of parasites may result in underestimation o...
Preprint
Background: Vaccine protection from COVID-19 has been shown to decline with time-since-vaccination and against SARS-CoV-2 variants. Protection against severe COVID-19 is higher than against symptomatic infection, and also appears relatively preserved over time and against variants. Although Protection protection from symptomatic SARS-CoV-2 infectio...
Preprint
Several studies show neutralizing antibody levels are an important correlate of immune protection from COVID-19 and have estimated the relationship between neutralizing antibodies and protection. However, a number of these studies appear to yield quite different estimates of the level of neutralizing antibodies required for protection. Here we show...
Article
Full-text available
Genetically distinct variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged since the start of the COVID-19 pandemic. Over this period, we developed a rapid platform (R-20) for viral isolation and characterization using primary remnant diagnostic swabs. This, combined with quarantine testing and genomics surveillance,...
Article
Vaccination against SARS-CoV-2 protects from infection and improves clinical outcomes in breakthrough infections, likely reflecting residual vaccine-elicited immunity and recall of immunological memory. Here, we define the early kinetics of spike-specific humoral and cellular immunity after vaccination of seropositive individuals and after Delta or...
Preprint
A key characteristic of Plasmodium vivax parasites is their ability to adopt a latent liver-stage form called hypnozoites, able to cause relapse of infection months or years after a primary infection. Relapses of infection through hypnozoite activation are a major contributor to blood-stage infections in P vivax endemic regions and are thought to b...
Preprint
In malaria endemic regions, transmission of Plasmodium falciparum parasites is often seasonal with very low transmission during the dry season and high transmission in the wet season. Parasites survive the dry season within some individuals who experience prolonged carriage of parasites and are thought to 'seed' infection in the next transmission s...
Article
Full-text available
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination elicit CD4+ T cell responses to the spike protein, including circulating follicular helper T (cTFH) cells that correlate with neutralizing antibodies. Using a novel HLA-DRB1*15:01/S751 tetramer to track spike-specific CD4+ T cells, we show that primary infection...
Article
We examined antibody and memory B cell responses longitudinally for ∼9-10 months after primary 2-dose SARS-CoV-2 mRNA vaccination and 3 months after a 3rd dose. Antibody decay stabilized between 6 to 9 months and antibody quality continued to improve for at least 9 months after 2-dose vaccination. Spike- and RBD-specific memory B cells remained dur...
Article
The rapid development of multiple vaccines providing strong protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been a major achievement. There is now compelling evidence for the role of neutralizing antibodies in protective immunity. T cells may play a role in resolution of primary SARS-CoV-2 infection, and t...
Preprint
Background A large number of studies have been carried out involving passive antibody administration for the treatment and prophylaxis of COVID-19 and have shown variable efficacy. However, the determinants of treatment effectiveness have not been identified. Here we aimed to aggregate all available data on randomised controlled trials of passive a...
Article
Full-text available
The emergence of Omicron (Pango lineage B.1.1.529), first identified in Botswana and South Africa, may compromise vaccine effectiveness and lead to re-infections¹. We investigated whether Omicron escapes antibody neutralization in South Africans vaccinated with Pfizer BNT162b2. We also investigated if Omicron requires the ACE2 receptor to infect ce...
Preprint
Despite a clear role in protective immunity, the durability and quality of antibody and memory B cell responses induced by mRNA vaccination, particularly by a 3 rd dose of vaccine, remains unclear. Here, we examined antibody and memory B cell responses in a cohort of individuals sampled longitudinally for ∼9-10 months after the primary 2-dose mRNA...
Article
Full-text available
Background Artemisinin-based combination therapy (ACT) has been a mainstay for malaria prevention and treatment. However, emergence of drug resistance has incentivised development of new drugs. Defining the kinetics with which circulating parasitized red blood cells (pRBC) are lost after drug treatment, referred to as the “parasite clearance curve”...
Preprint
The immune system is stratified into layers of specialized cells with distinct functions. Recently, Lin28b was shown to serve as a master regulator of fetal lymphopoiesis, programming the development of more innate-like lymphocytes in early life. However, it remains unclear whether Lin28b specifies innate functions in more conventional adaptive lym...
Article
Full-text available
Background: Analytical treatment interruptions (ATI) are pauses of antiretroviral therapy (ART) in the context of HIV cure trials. They are the gold standard in determining if interventions being tested can achieve sustained virological control in the absence ART. However, withholding ART comes with risks and discomforts to the trial participant....
Article
The vaccine candidate CVnCoV (CUREVAC) showed surprisingly low efficacy in a recent phase 3 trial compared with other mRNA vaccines. Here we show that the low efficacy follows from the dose used and the presence of SARS-CoV-2 variants, and is predicted by the neutralising antibody response induced by the vaccine.
Preprint
Full-text available
Genetically distinct viral variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been recorded since January 2020. Over this time global vaccine programs have been introduced, contributing to lowered COVID-19 hospitalisation and mortality rates, particularly in the first world. In late 2021, the Omicron (B.1.1.529) virus var...
Article
Full-text available
The emergence of Omicron (Pango lineage B.1.1.529), first identified in Botswana and South Africa, may compromise vaccine effectiveness and lead to re-infections1. We investigated whether Omicron escapes antibody neutralization in South Africans vaccinated with Pfizer BNT162b2. We also investigated if Omicron requires the ACE2 receptor to infect ce...
Preprint
From late 2020 the world observed the rapid emergence of many distinct SARS-CoV-2 variants. At the same time, pandemic responses resulted in significant global vaccine rollouts that have now significantly lowered Covid-19 hospitalisation and mortality rates in the developed world. Unfortunately, in late 2021, the variant Omicron (B.1.1.529) emerged...
Preprint
In the studies to date, the estimated fold-drop in neutralisation titre against Omicron ranges from 2- to over 20-fold depending on the study and serum tested. Collating data from the se results in a combined estimate of the fold drop in neutralisation titre against Omicron of 9.7 (95%CI 5.5-17.1). We use our previously established model to predict...
Preprint
Full-text available
The emergence of the SARS-CoV-2 Omicron variant, first identified in South Africa, may compromise the ability of vaccine and previous infection (1) elicited immunity to protect against new infection. Here we investigated whether Omicron escapes antibody neutralization elicited by the Pfizer BNT162b2 mRNA vaccine in people who were vaccinated only o...
Article
Full-text available
Little is known about how specific individual viral lineages replicating systemically during acute Human Immunodeficiency Virus or Simian Immunodeficiency Virus (HIV/SIV) infection persist into chronic infection. In this study, we use molecularly barcoded SIV (SIVmac239M) to track distinct viral lineages for 12 weeks after intravenous (IV) or intra...
Article
Full-text available
Broadly neutralising antibodies (bNAbs) may play an important role in future strategies for HIV control. The development of anti-drug antibody (ADA) responses can reduce the efficacy of passively transferred bNAbs but the impact of ADA is imperfectly understood. We previously showed that therapeutic administration of the anti-HIV bNAb PGT121 (eithe...
Article
Full-text available
Objectives SARS-CoV-2 can be transmitted by aerosols, and the ocular surface may be an important route of transmission. Little is known about protective antibody responses to SARS-CoV-2 in tears after infection or vaccination. We analysed the SARS-CoV-2-specific IgG and IgA responses in human tears after either COVID-19 infection or vaccination. M...
Article
Background Circadian transcription factors that regulate cell-autonomous circadian clocks can also increase HIV transcription in vitro. We aimed to determine if circadian variation in HIV transcription exists in people living with HIV (PLHIV) on antiretroviral therapy (ART). Methods We performed a prospective observational study of male PLHIV on A...
Article
Full-text available
Immune memory after vaccination Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has proven highly effective at preventing severe COVID-19. However, the evolution of viral variants, and waning antibody levels over time, raise questions regarding the longevity of vaccine-induced immune protection. Goel et al . examine...
Preprint
Full-text available
CD4+ T cells play a critical role in the immune response to viral infection. SARS-CoV-2 infection and vaccination elicit strong CD4+ T cell responses to the viral spike protein, including circulating T follicular helper (cTFH) cells that correlate with the development of neutralising antibodies. Here we use a novel HLA-DRB1*15:01/S751 tetramer to p...
Article
Reformulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines with variant strains is being pursued to combat the global surge in infections. We hypothesize that this may be suboptimal due to immune imprinting from earlier vaccination or infection with the original SARS-CoV-2 strain. New strategies may be needed to improve eff...
Article
Full-text available
Potent neutralising monoclonal antibodies are one of the few agents currently available to treat COVID-19. SARS-CoV-2 variants of concern (VOC) that carry multiple mutations in the viral spike protein can exhibit neutralisation resistance, potentially impacting the effectiveness of some antibody-based therapeutics. Here, generation of a diverse pan...
Preprint
Full-text available
SARS-CoV-2 mRNA vaccines have shown remarkable efficacy, especially in preventing severe illness and hospitalization. However, the emergence of several variants of concern and reports of declining antibody levels have raised uncertainty about the durability of immune memory following vaccination. In this study, we longitudinally profiled both antib...
Preprint
Maturation rate of malaria parasites within red blood cells (RBC) can be influenced by host nutrient status or circadian rhythm. Here, we observed in mice that systemic host inflammation, induced by lipopolysaccharide (LPS) conditioning or ongoing acute malaria infection, slowed the progression of a single cohort of parasites from one generation of...
Preprint
A number of SARS-CoV-2 variants of concern (VOC) have been identified that partially escape serum neutralisation activity elicited by current vaccines. Recent studies have also shown that vaccines demonstrate reduced protection against symptomatic infection with SARS-CoV-2 variants. Here we integrate published data on in vitro neutralisation and cl...
Preprint
Full-text available
Objectives SARS-CoV-2 can be transmitted by aerosols and the ocular surface may be an important route of transmission. Little is known about protective antibody responses to SARS-CoV-2 in tears after infection or vaccination. We analysed SARS-CoV-2 specific IgG and IgA responses in human tears after either COVID-19 infection or vaccination. Methods...
Preprint
A recent study analysed the relationship between neutralising antibody response and protection from SARS-CoV-2 infection across eight vaccines platforms. The efficacy results from a phase 2b/3 trial of a ninth vaccine candidate, CVnCoV (CUREVAC), was announced on 16 June 2021. The low efficacy of this new mRNA vaccine, which showed only 47% protect...
Article
Full-text available
Analytical treatment interruptions (ATIs) of antiretroviral therapy (ART) play a central role in evaluating the efficacy of HIV-1 treatment strategies targeting virus that persists despite ART. However, it remains unclear if ATIs alter the rebound-competent viral reservoir (RCVR), the virus population that persists during ART and from which viral r...
Article
Full-text available
Significance Neutralizing antibodies are important for immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and as therapeutics for the prevention and treatment of COVID-19. We identified high-affinity nanobodies against SARS-CoV-2 receptor-binding domain and found that nanobody cocktails consisting of two noncompeting nano...
Preprint
Little is known about how individual virus lineages replicating during acute Human Immunodeficiency Virus or Simian Immunodeficiency Virus (HIV/SIV) infection persist into chronic infection. In this study, we use molecularly barcoded SIV (SIVmac239M) to track distinct viral lineages for 12 weeks after intravenous and intrarectal challenge in macaqu...
Article
Full-text available
The capacity of antibodies to engage with immune cells via the Fc region is important in preventing and controlling many infectious diseases. The evolution of such antibodies during convalescence from COVID-19 is largely unknown. We develop assays to measure Fc-dependent antibody functions against SARS-CoV-2 spike (S)-expressing cells in serial sam...
Article
Immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is central to long-term control of the current pandemic. Despite our rapidly advancing knowledge of immune memory to SARS-CoV-2, understanding how these responses translate into protection against reinfection at both the individual and population levels remains a maj...
Preprint
Full-text available
Both previous infection and vaccination have been shown to provide potent protection from COVID-19. However, there are concerns that waning immunity and viral variation may lead to a loss of protection over time. Predictive models of immune protection are urgently needed to identify immune correlates of protection to assist in the future deployment...
Article
To define the contribution of CD8+ T cell responses to control of SIV reactivation during and following antiretroviral therapy (ART), we determined the effect of long-term CD8+ T cell depletion using a rhesusized anti-CD8β monoclonal antibody (mAb) on barcoded SIVmac239 dynamics on stable ART and after ART cessation in Rhesus Macaques (RMs). Among...
Article
Full-text available
The durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with individual...
Article
Full-text available
Background The generation of accurate and reproducible viral sequence data is necessary to understand the diversity present in populations of RNA viruses isolated from clinical samples. While various sequencing methods are available, they often require high quality templates and high viral titer to ensure reliable data. Methods We modified a multi...
Preprint
Full-text available
The capacity of antibodies to engage with innate and adaptive immune cells via the Fc region is important in preventing and controlling many infectious diseases, and is likely critical in SARS-CoV-2 infection. The evolution of such antibodies during convalescence from COVID-19 is largely unknown. We developed novel assays to measure Fc-dependent an...
Article
Full-text available
The dynamics of CD4⁺ T cell memory development remain to be examined at genome scale. In malaria-endemic regions, antimalarial chemoprevention protects long after its cessation and associates with effects on CD4⁺ T cells. We applied single-cell RNA sequencing and computational modelling to track memory development during Plasmodium infection and tr...
Article
When nanoparticles interact with human blood, a multitude of plasma components adsorb onto the surface of the nanoparticles, forming a biomolecular corona. Corona composition is known to be influenced by the chemical composition of nanoparticles. In contrast, the possible effects of variations in the human blood proteome between healthy individuals...
Article
The rapid scale-up of research on coronavirus disease 2019 (COVID-19) has spawned a large number of potential vaccines and immunotherapies, accompanied by a commensurately large number of in vitro assays and in vivo models to measure their effectiveness. These assays broadly have the same end-goal — to predict the clinical efficacy of prophylactic...
Article
Background Artemisinin derivatives are the leading class of antimalarial drugs due to their rapid onset of action and rapid clearance of circulating parasites. The parasite clearance (PC) half-life measures the rate of loss of parasites from blood after treatment, and this is currently used to assess antimalarial activity of novel agents and to mon...
Preprint
The durability of infection-induced SARS-CoV-2 immunity has major implications for public health mitigation and vaccine development. Animal studies and the scarcity of confirmed re-infection suggests immune protection is likely, although the durability of this protection is debated. Lasting immunity following acute viral infection requires maintena...
Article
Full-text available
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has dramatically expedited global vaccine development efforts1,2,3, most targeting the viral ‘spike’ glycoprotein (S). S localizes on the virion surface and mediates recognition of cellular receptor angiotensin-converting enzyme 2 (ACE2)4,5,6. Eliciting neutralizing antibodie...
Article
Antiretroviral therapy (ART) provides effective control of human immunodeficiency virus (HIV) replication and maintains viral loads of HIV at undetectable levels. Interruption of ART causes rapid recrudescence of HIV plasma viremia due to reactivation of latently HIV-infected cells. Here, we characterize the timing of both the initial and subsequen...
Article
Full-text available
Resistance to the artemisinin derivatives, our most effective antimalarial drugs, has not manifest as a classical resistance phenotype in which parasites can tolerate higher drug concentrations. Instead, resistant parasites have an altered maturation. We hypothesize that the short half-life of artemisinin concentrations is an unanticipated driver o...
Article
Full-text available
Each year, 4.3 million pregnant women are exposed to malaria risk in Latin America and the Caribbean. Plasmodium vivax causes 76% of the regional malaria burden and appears to be less affected than P. falciparum by current elimination efforts. This is in part due to the parasite's ability to stay dormant in the liver and originate relapses within m...
Preprint
Full-text available
Background: The generation of accurate and reproducible viral sequence data is necessary to understand the diversity present in populations of RNA viruses isolated from clinical samples. While various sequencing methods are available, they often require high quality templates and high viral titer to ensure reliable data. Methods: We modified a mult...
Preprint
Full-text available
Background: The generation of accurate and reproducible viral sequence data is necessary to understand the diversity present in populations of RNA viruses isolated from clinical samples. While various sequencing methods are available, they often require high quality templates and high viral titer to ensure reliable data. Methods: We modified a mult...