Miles P Davenport

Kirby Institute

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...

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...

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...

Multiple monoclonal antibodies have been shown to be effective for both prophylaxis and therapy for SARS-CoV-2 infection. Here we aggregate data from randomized controlled trials assessing the use of monoclonal antibodies (mAb) in preventing symptomatic SARS-CoV-2 infection. We use data on the in vivo concentration of mAb and the associated protect...

Background Surrogates of antiviral efficacy are needed for COVID-19. We investigated the relationship between the virological effect of treatment and clinical efficacy as measured by progression to severe disease in unvaccinated outpatients treated for mild to moderate COVID-19. Methods We searched PubMed, Scopus and medRxiv from inception to 27 t...

Mpox outbreaks in Central Africa have been declared a public health emergency of international concern by the World Health Organization. Fortunately, real-world effectiveness studies of the MVA-BN vaccine indicate that it has an effectiveness of 74% after one dose, and 82% after two doses against mpox. However, given the very limited supply of vacc...

The ongoing evolution of the SARS-CoV-2 virus has led to a move to update vaccine antigens in 2022 and 2023. These updated antigens were chosen and approved based largely on in vitro neutralisation titres against recent SARS-CoV-2 variants. However, unavoidable delays in vaccine manufacture and distribution meant that the updated booster vaccine wa...

Lipid nanoparticle mRNA vaccines are an exciting but emerging technology used in humans. There is limited understanding of the factors that influence their biodistribution and immunogenicity. Antibodies to poly(ethylene glycol) (PEG), which is on the surface of the lipid nanoparticle, are detectable in humans and boosted by human mRNA vaccination....

A multiplexed, lentivirus-based pseudovirus neutralisation assay (pVNT) was developed for high-throughput measurement of neutralising antibodies (nAbs) against three distinct SARS-CoV-2 spike variants. Intra-assay variability was minimised by optimising the plate layout and determining an optimal percentage transduction for the pseudovirus inoculum...

Persistence of the rebound-competent viral reservoir (RCVR) within the CD4⁺ T cell compartment of people living with HIV remains a major barrier to HIV cure. Here, we determined the effects of the pan-lymphocyte-depleting monoclonal antibody (mAb) alemtuzumab on the RCVR in SIVmac239-infected rhesus macaques (RM) receiving antiretroviral therapy (A...

Lipid nanoparticle mRNA vaccines are an exciting but new technology used in humans. There is limited understanding of factors that influence their biodistribution and immunogenicity. Antibodies to polyethylene glycol (PEG), which is on the surface of the lipid nanoparticle, are detectable in humans and boosted by human mRNA vaccination. We hypothes...

Background: There is uncertainty around the timing of booster vaccination against COVID-19 in highly vaccinated populations during the present endemic phase of COVID-19. Studies focused on primary vaccination have previously suggested improved immunity after delaying immunisation. Methods: We conducted a randomised controlled trial (Nov 2022 - A...

Lymphopenia is a common feature of acute COVID-19 and is associated with increased disease severity and 30-day mortality. Here we aim to define the demographic and clinical characteristics that correlate with lymphopenia in COVID-19 and determine if lymphopenia is an independent predictor of poor clinical outcome. We analysed the ENTER-COVID (Epide...

Population-level waning of protection following immunising exposures is an important determinant of susceptibility to COVID-19 outbreaks. This work outlines an individual-based model (IBM) for the transmission and clinical impact of SARS-CoV-2 that explicitly represents the immunological response to vaccination and infection of each individual. The...

The Modified Vaccinia Ankara vaccine developed by Bavarian Nordic (MVA-BN) was widely deployed to prevent mpox during the 2022 global outbreak. This vaccine was initially approved for mpox based on its reported immunogenicity (from phase I/II trials) and effectiveness in animal models, rather than evidence of clinical efficacy. However, no validate...

The rebound competent viral reservoir (RCVR)–virus that persists during antiretroviral treatment (ART) and can reignite systemic infection when treatment is stopped–is the primary barrier to eradicating HIV. We used time to initiation of ART during primary infection of rhesus macaques (RMs) after intravenous challenge with barcoded SIVmac239 as a m...

Background Surrogates of antiviral efficacy are needed for COVID-19. We aimed to investigate the relationship between the virological effect of treatment and clinical efficacy as measured by progression to severe disease in outpatients treated for mild-to-moderate COVID-19. Methods In this systematic review and meta-analysis, we searched PubMed, Sc...

Objectives Amino acid variations across more than 30 immunoglobulin (Ig) allotypes may introduce structural changes that influence recognition by anti‐Ig detection reagents, consequently confounding interpretation of antibody responses, particularly in genetically diverse cohorts. Here, we assessed a panel of commercial monoclonal anti‐IgG1 clones...

CD8 ⁺ T cells are classically recognized as adaptive lymphocytes based on their ability to recognize specific foreign antigens and mount memory responses. However, recent studies indicate that some antigen-inexperienced CD8 ⁺ T cells can respond to innate cytokines alone in the absence of cognate T cell receptor stimulation, a phenomenon referred t...

Human infection challenge permits in-depth, early, and pre-symptomatic characterization of the immune response, enabling the identification of factors that are important for viral clearance. Here, we performed intranasal inoculation of 34 young adult, seronegative volunteers with a pre-Alpha severe acute respiratory syndrome coronavirus 2 (SARS-CoV...

The ongoing evolution of the SARS-CoV-2 virus has led to a move to update vaccine antigens in 2022 and 2023. These updated antigens were chosen and approved based on in vitro neutralisation titres against recent SARS-CoV-2 variants. However, unavoidable delays in viral manufacture and distribution meant that the updated booster vaccine was no longe...

HIV rapidly rebounds after interruption of antiretroviral therapy (ART). HIV-specific CD8⁺ T cells may act to prevent early events in viral reactivation. However, the presence of viral immune escape mutations may limit the effect of CD8⁺ T cells on viral rebound. Here, we studied the impact of CD8 immune pressure on post-treatment rebound of barcod...

The Modified Vaccinia Ankara vaccine developed by Bavarian Nordic (MVA-BN) was widely deployed to prevent Mpox during the 2022 global outbreak. This vaccine was initially approved for Mpox based on its reported immunogenicity and effectiveness in animal models, rather than evidence of clinical efficacy. However no validated correlate of protection...

One approach to ‘functional cure’ of HIV infection is to induce durable control of HIV replication after the interruption of antiretroviral therapy (ART). However, the major factors that determine the viral ‘setpoint’ level after treatment interruption are not well understood. Here we combine data on ART interruption following SIV infection for 124...

Understanding mucosal antibody responses from SARS-CoV-2 infection and/or vaccination is crucial to develop strategies for longer term immunity, especially against emerging viral variants. We profiled serial paired mucosal and plasma antibodies from COVID-19 vaccinated only vaccinees (vaccinated, uninfected), COVID-19-recovered vaccinees (recovered...

Mucosal antibodies play a key role in protection against breakthrough COVID-19 infections and emerging viral variants. Intramuscular adenovirus-based vaccination (Vaxzevria) only weakly induces nasal IgG and IgA responses, unless vaccinees have been previously infected. However, little is known about how Vaxzevria vaccination impacts the ability of...

Human infection challenge permits characterisation of the associated immune response in unparalleled depth, enabling evaluation of early pre-symptomatic immune changes and the dynamic immune factors important for viral clearance. Here, 34 healthy young adult volunteers, seronegative to SARS-CoV-2, were inoculated with a D614G-containing pre-Alpha S...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection of vaccinated individuals is increasingly common with the circulation of highly immune evasive and transmissible Omicron variants. Here, we report the dynamics and durability of recalled spike-specific humoral immunity following Omicron BA.1 or BA.2 breakthrough inf...

Maturation rates of malaria parasites within red blood cells (RBCs) can be influenced by host nutrient status and circadian rhythm; whether host inflammatory responses can also influence maturation remains less clear. Here, we observed that systemic host inflammation induced in mice by an innate immune stimulus, lipopolysaccharide (LPS), or by ongo...

Transmitted/founder (TF) simian-human immunodeficiency viruses (SHIVs) express HIV-1 envelopes modified at position 375 to efficiently infect rhesus macaques while preserving authentic HIV-1 Env biology. SHIV.C.CH505 is an extensively characterized virus encoding the TF HIV-1 Env CH505 mutated at position 375 shown to recapitulate key features of H...

High-risk groups, including Indigenous people, are at risk of severe COVID-19. Here we found that Australian First Nations peoples elicit effective immune responses to COVID-19 BNT162b2 vaccination, including neutralizing antibodies, receptor-binding domain (RBD) antibodies, SARS-CoV-2 spike-specific B cells, and CD4⁺ and CD8⁺ T cells. In First Nat...

Pregnancy poses a greater risk for severe COVID-19; however, underlying immunological changes associated with SARS-CoV-2 during pregnancy are poorly understood. We defined immune responses to SARS-CoV-2 in unvaccinated pregnant and nonpregnant women with acute and convalescent COVID-19, quantifying 217 immunological parameters. Humoral responses to...

Understanding mucosal antibody responses from SARS-CoV-2 infection and/or vaccination is crucial to develop strategies for longer term immunity, especially against emerging viral variants. We profiled serial paired mucosal and plasma antibodies from: COVID-19 vaccinated only vaccinees (vaccinated, uninfected), COVID-19 recovered vaccinees (convales...

Vaccine protection from symptomatic SARS-CoV-2 infection has been shown to be strongly correlated with neutralising antibody titres; however, this has not yet been demonstrated for severe COVID-19. To explore whether this relationship also holds for severe COVID-19, we performed a systematic search for studies reporting on protection against differ...

Booster vaccination for the prevention of Coronavirus Disease 2019 (COVID-19) is required to overcome loss of protection due to waning immunity and the spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Studies have assessed the ability of existing ancestral-based vaccines as well as novel variant-modified vaccin...

SARS-CoV-2 breakthrough infection of vaccinated individuals is increasingly common with the circulation of highly immune evasive and transmissible Omicron variants. Here, we report the dynamics and durability of recalled spike-specific humoral immunity following BA.1 or BA.2 breakthrough infection, with longitudinal sampling up to 8 months post-inf...

Background 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 tra...

Several studies have shown that neutralizing antibody levels correlate with immune protection from COVID-19 and have estimated the relationship between neutralizing antibodies and protection. However, results of these studies vary in terms of estimates of the level of neutralizing antibodies required for protection. By normalizing antibody titers,...

Although the protective role of neutralizing antibodies against COVID-19 is well established, questions remain about the relative importance of cellular immunity. Using 6 pMHC multimers in a cohort with early and frequent sampling, we define the phenotype and kinetics of recalled and primary T cell responses following Delta or Omicron breakthrough...

Persistence of the human immunodeficiency virus type-1 (HIV-1) latent reservoir in infected individuals remains a problem despite fully suppressive antiretroviral therapy (ART). While reservoir formation begins during acute infection, the mechanisms responsible for its establishment remain unclear. CD8 ⁺ T cells are important during the initial con...

While the protective role of neutralising antibodies against COVID-19 is well-established, questions remain about the relative importance of cellular immunity. Using 6 pMHC-multimers in a cohort with early and frequent sampling we define the phenotype and kinetics of recalled and primary T cell responses following Delta or Omicron breakthrough infe...

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...

Transmitted/founder (TF) simian-human immunodeficiency viruses (SHIVs) express HIV-1 envelopes modified at position 375 to efficiently infect rhesus macaques while preserving authentic HIV-1 Env biology. TF SHIV.C.CH505 is an extensively characterized virus shown to recapitulate key features of HIV-1 immunobiology, including CCR5-tropism, a tier 2...

Multiple monoclonal antibodies have been shown to be effective for both prophylaxis and therapy for SARS-CoV-2 infection. Here we aggregate data from randomized controlled trials assessing the use of monoclonal antibodies in preventing symptomatic SARS-CoV-2 infection. We use data on changes in the in vivo concentration of monoclonal antibodies, an...

A recently published article has confirmed that a novel immunization method of sustained and escalating antigen delivery augments the magnitude, quality and durability of humoral immune responses.

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...

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...

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...

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...

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,...

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...

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...

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...

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...

Although pregnancy poses a greater risk for severe COVID-19, the underlying immunological changes associated with SARS-CoV-2 infection during pregnancy are poorly understood. We defined immune responses to SARS-CoV-2 in pregnant and non-pregnant women during acute and convalescent COVID-19 up to 258 days post symptom onset, quantifying 217 immunolo...

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...

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...

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...