Adam Wheatley

• PhD
• University of Melbourne

This study investigates the humoral and cellular immune responses and health-related quality of life measures in individuals with mild to moderate long COVID (LC) compared to age and gender matched recovered COVID-19 controls (MC) over 24 months. LC participants show elevated nucleocapsid IgG levels at 3 months, and higher neutralizing capacity up...

This study investigated the humoral and cellular immune responses in individuals with long COVID (LC) compared to age and gender matched recovered COVID-19 controls (MC) over 24-months. LC participants showed elevated spike and nucleocapsid IgG levels, higher neutralizing capacity, and increased spike- and nucleocapsid-specific CD4+ T cells, PD-1,...

Plasma samples taken at different time points from donors who received either AstraZeneca (Vaxzevria) or Pfizer (Comirnaty) or Moderna (Spikevax) coronavirus disease-19 (COVID-19) vaccine were assessed in virus neutralization assays against Delta and Omicron variants of concern and a reference isolate (VIC31). With the Pfizer vaccine there was 6-8-...

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...

Understanding the generation of immunity to SARS-CoV-2 in lymphoid tissues draining the site of infection has implications for immunity to SARS-CoV-2. We performed tonsil biopsies under local anesthesia in 19 subjects who had recovered from SARS-CoV-2 infection 24-225 d previously. The biopsies yielded >3 million cells for flow cytometric analysis...

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...

Influenza viruses circulate globally, causing seasonal influenza outbreaks. Although antibody-inducing vaccines are the most effective way to combat seasonal infections, current vaccines can have poor efficacy, especially in children and immunocompromised individuals. We investigated the immunogenicity and efficacy of monovalent and quadrivalent fo...

Plasma samples taken at different time points from donors who received either AstraZeneca (Vaxzevria) or Pfizer (Comirnaty) or Moderna (Spikevax) coronavirus disease-19 (COVID-19) vaccine were assessed in virus neutralization assays against Delta and Omicron variants of concern and a reference isolate (VIC31). With the Pfizer vaccine there was 6-8...

Following infection with SARS-CoV-2, virus-specific antibodies are generated which can both neutralise virions and clear infection via Fc effector functions. The importance of IgG antibodies for protection and control of SARS-CoV-2 has been extensively reported. In comparison, other antibody isotypes including IgA have been poorly characterized. He...

Recent studies have established that memory B cells, largely thought to be circulatory in the blood, can take up long-term residency in inflamed tissues, analogous to widely described tissue-resident T cells. The dynamics of recruitment and retention of memory B cells to tissues and their immunological purpose remains unclear. Here, we characterize...

Humans commonly have low level antibodies to poly(ethylene) glycol (PEG) due to environmental exposure. Lipid nanoparticle mRNA vaccines for SARS-CoV-2 contain small amounts of PEG but it is not known if PEG antibodies are enhanced by vaccination and if there are any consequences. We studied plasma from 55 people receiving the Comirnaty (Pfizer-Bio...

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...

COVID-19 has become a major cause of global mortality and driven massive health and economic disruptions. Mass global vaccination offers the most efficient pathway towards ending the pandemic. The development and deployment of first-generation COVID-19 vaccines, encompassing mRNA or viral vectors, has proceeded at a phenomenal pace. Going forward,...

Background As vaccines against SARS-CoV-2 are now being rolled out, a better understanding of immunity to the virus, whether from infection, or passive or active immunisation, and the durability of this protection is required. This will benefit from the ability to measure antibody-based protection to SARS-CoV-2, ideally with rapid turnaround and wi...

New studies highlight the immunological benefits of COVID-19 vaccine boosters, but questions remain over how to best make use of a limited global supply.

Vaccination remains the most effective mechanism to reduce the impact of COVID‐19. Induction of neutralizing antibodies is a strong correlate of protection from infection and severe disease. An understanding of the cellular events that underpin the generation of effective neutralizing antibodies is therefore key to the development of efficacious va...

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...

Significance Indigenous populations worldwide are highly susceptible to influenza virus infections. Vaccination with inactivated virus is highly recommended to protect Indigenous populations, including Indigenous Australians. There is no study to date that assessed immune responses induced by the inactivated seasonal influenza vaccine in the Indige...

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...

Humans are exposed to influenza virus through periodic infections. Due to these repeated exposures, human populations commonly have elevated antibody titres targeting the conserved internal influenza virus nucleoprotein (NP). Despite the presence of anti‐NP antibodies, humans are acutely susceptible to drifted influenza viruses with antigenically d...

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...

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...

The SARS-CoV-2 pandemic has seen a notable global reduction in influenza cases of both influenza A and B viruses. In particular, the B/Yamagata lineage has not been isolated from April 2020 to August 2021, suggesting that this influenza lineage may have become extinct, which may provide opportunities for improving availability and effectiveness of...

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...

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...

Background HIV-1 infections occur following viral exposure at anogenital mucosal surfaces in the presence of semen. Semen contains immunosuppressive and pro-inflammatory factors. Semen from HIV-1-infected donors contains anti-HIV-1 antibodies. We assessed if passively infused anti-HIV-1 neutralizing antibody conferred protection from rectal SHIVSF1...

CD8⁺ T cells play an important role in vaccination and immunity against SARS-CoV-2 infection. Although numerous SARS-CoV-2 CD8⁺ T cell epitopes have been identified, the molecular basis underpinning T cell receptor (TCR) recognition of SARS-CoV-2-specific T cells remains unknown. The T cell response directed towards SARS-CoV-2 spike protein-derived...

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...

The SARS-CoV-2 Receptor Binding Domain (RBD) is both the principal target of neutralizing antibodies, and one of the most rapidly evolving domains, which can result in the emergence of immune escape mutations limiting the effectiveness of vaccines and antibody therapeutics. To facilitate surveillance, we developed a rapid, high-throughput, multiple...

Characterization of germinal center B and T cell responses yields critical insights into vaccine immunogenicity. Nonhuman primates are a key preclinical animal model for human vaccine development, allowing both lymph node (LN) and circulating immune responses to be longitudinally sampled for correlates of vaccine efficacy. However, patterns of vacc...

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...

In‐depth understanding of human T cell‐mediated immunity in COVID‐19 is needed if we are to optimize vaccine strategies and immunotherapies. Identification of SARS‐CoV‐2 T cell epitopes and generation of peptide‐HLA tetramers facilitates direct ex vivo analyses of SARS‐CoV‐2‐specific T cells and their T cell receptor (TCR) repertoires. We utilized...

Vaccination represents the best line of defense against infectious diseases and is crucial in curtailing pandemic spread of emerging pathogens to which a population has limited immunity. In recent years, mRNA vaccines have been proposed as the new frontier in vaccination, owing to their facile and rapid development while providing a safer alternati...

How innate and adaptive immune responses work in concert to resolve influenza disease is yet to be fully investigated in one single study. Here, we utilize longitudinal samples from patients hospitalized with acute influenza to understand these immune responses. We report the dynamics of 18 important immune parameters, related to clinical, genetic...

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...

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...

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...

As vaccines against SARS-CoV-2 are now being rolled out, a better understanding of immunity to the virus; whether through infection, or passive or active immunisation, and the durability of this protection is required. This will benefit from the ability to measure SARS-CoV-2 immunity, ideally with rapid turnaround and without the need for laborator...

The emergence of SARS-CoV-2 and subsequent COVID-19 pandemic has resulted in a significant global public health burden, leading to an urgent need for effective therapeutic strategies. In this article, we review the role of SARS-CoV-2 neutralizing antibodies (nAbs) in the clinical management of COVID-19 and provide an overview of recent randomized c...

The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pande...

To better understand primary and recall T cell responses during COVID-19, it is important to examine unmanipulated SARS-CoV-2-specific T cells. Using peptide-HLA tetramers for direct ex vivo analysis, we characterized CD8⁺ T cells specific for SARS-CoV-2 epitopes in COVID-19 patients and unexposed individuals. Unlike CD8⁺ T cells directed towards s...

Objectives Endemic human coronaviruses (hCoVs) circulate worldwide but cause minimal mortality. Although seroconversion to hCoV is near ubiquitous during childhood, little is known about hCoV‐specific T‐cell memory in adults. Methods We quantified CD4 T‐cell and antibody responses to hCoV spike antigens in 42 SARS‐CoV‐2‐uninfected individuals. Ant...

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...

Influenza imparts an age-related increase in mortality and morbidity. The most effective countermeasure is vaccination; however, vaccines offer modest protection in older adults. To investigate how ageing impacts the memory B cell response we tracked haemagglutinin specific B cells by indexed flow sorting and single cell RNA sequencing in twenty he...

SARS-CoV-2 vaccines are advancing into human clinical trials, with emphasis on eliciting high titres of neutralising antibodies against the viral spike (S). However, the merits of broadly targeting S versus focusing antibody onto the smaller receptor binding domain (RBD) are unclear. Here we assess prototypic S and RBD subunit vaccines in homologou...

Despite remarkable successes of immunization in protecting public health, safe and effective vaccines against a number of life‐threatening pathogens such as HIV, ebola, influenza, and SARS‐CoV‐2 remain urgently needed. Subunit vaccines can avoid potential toxicity associated with traditional whole virion‐inactivated and live‐attenuated vaccines; ho...

Objectives As the world transitions into a new era of the COVID‐19 pandemic in which vaccines become available, there is an increasing demand for rapid reliable serological testing to identify individuals with levels of immunity considered protective by infection or vaccination. Methods We used 34 SARS‐CoV‐2 samples to perform a rapid surrogate vi...

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...

SARS-CoV-2 causes a spectrum of COVID-19 disease, the immunological basis of which remains ill-defined. We analysed 85 SARS-CoV-2-infected individuals at acute and/or convalescent timepoints, up to 102 days post-symptom onset, quantifying 184 immunological parameters. Acute COVID-19 presented with high levels of IL-6, IL-18 and IL-10 and broad acti...

The diversity of circulating human B cells is unknown. We use single-cell RNA sequencing (RNA-seq) to examine the diversity of both antigen-specific and total B cells in healthy subjects and malaria-exposed individuals. This reveals two B cell lineages: a classical lineage of activated and resting memory B cells and an alternative lineage, which in...

Endemic human coronaviruses (hCoV) circulate worldwide but cause minimal mortality. Although seroconversion to hCoV is near ubiquitous during childhood, little is known about hCoV-specific T cell memory in adults. We quantified CD4 T cell and antibody responses to hCoV spike antigens in 42 SARS-CoV-2 uninfected individuals. T cell responses were wi...

The ferret is a key animal model for investigating the pathogenicity and transmissibility of important human viruses, and for the pre‐clinical assessment of vaccines. However, relatively little is known about the ferret immune system, due in part to a paucity of ferret‐reactive reagents. In particular, T follicular helper (Tfh) cells are critical i...

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...

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...

Vaccine development has been hampered by the long lead times and the high cost required to reach the market. The 2020 pandemic, caused by a new coronavirus (SARS-CoV-2) that was first reported in late 2019, has seen unprecedented rapid activity to generate a vaccine, which belies the traditional vaccine development cycle. Critically, much of this p...

Influenza virus infection is a global public health threat. Current seasonal influenza vaccines are efficacious only when vaccine strains are matched with circulating strains. There is a critical need for developing “universal” vaccines that protect against all influenza viruses. HA stem is a promising target for developing broad-spectrum influenza...

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...

We report in-concert dynamics of 18 key immune parameters, related to clinical, genetic and virological factors, in patients hospitalized with influenza across different severity levels. Influenza disease was associated with correlated increases in IL6/IL-8/MIP-1; cytokines and lower antibody responses. Robust activation of circulating T follicular...

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...

Significance As the recall of CD8 ⁺ T cell memory promotes rapid recovery in, for example, influenza, we investigated circulating SARS-CoV-2−specific CD8 ⁺ T cells from COVID-19 patients. For two HLA-A*02:01 SARS-CoV-2−specific CD8 ⁺ T cell epitopes, we found that, while ex vivo frequencies of responding T cells were approximately fivefold higher t...

Antibody-based drugs and vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being expedited through preclinical and clinical development. Data from the study of SARS-CoV and other respiratory viruses suggest that anti-SARS-CoV-2 antibodies could exacerbate COVID-19 through antibody-dependent enhancement (ADE). Previou...

SARS-CoV-2 vaccines are advancing into human clinical trials, with emphasis on eliciting high titres of neutralising antibodies against the viral spike (S). However, the merits of broadly targeting S versus focusing antibody onto the smaller receptor binding domain (RBD) are unclear. Here we assessed prototypic S and RBD subunit vaccines in homolog...

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 antibod...

Characterisation of germinal centre B and T cell responses yields critical insights into vaccine immunogenicity. Non-human primates are a key pre-clinical animal model for human vaccine development, allowing both lymph node and circulating immune responses to be longitudinally sampled for correlates of vaccine efficacy. However, patterns of vaccine...

An improved understanding of human T-cell-mediated immunity in COVID-19 is important if we are to optimize therapeutic and vaccine strategies. Experience with influenza shows that infection primes CD8+ T-cell memory to shared peptides presented by common HLA types like HLA-A2. Following re-infection, cross-reactive CD8+ T-cells enhance recovery and...

Influenza remains a significant global public health burden, despite substantial annual vaccination efforts against circulating virus strains. As a result, novel vaccine approaches are needed to generate long‐lasting and universal broadly cross‐reactive immunity against distinct influenza virus strains and subtypes. Several new vaccine candidates a...

In article number 2002861, Thomas P. Davis, Stephen J. Kent, Nghia P. Truong, and co‐workers introduce an artificial microvascular network to characterize cellular interactions of nanomaterials under human blood flow conditions. This innovative platform is easy to set up in any lab and can be applied to future studies of any type of nanoparticles,...

The emergence of SARS-CoV-2 has driven a global research effort to identify medical countermeasures at an unprecedented pace. In this issue of Cell, Cao et al. identify thousands of SARS-CoV-2 neutralizing antibodies from convalescent donors. The authors improve our understanding of immunity against the coronavirus spike glycoprotein and detail nov...

A key concept in nanomedicine is encapsulating therapeutic or diagnostic agents inside nanoparticles to prolong blood circulation time and to enhance interactions with targeted cells. During circulation and depending on the selected application (e.g., cancer drug delivery or immune modulators), nanoparticles are required to possess low or high inte...

Vδ2⁺ T cells play a critical role in immunity to micro-organisms and cancer but exhibit substantial heterogeneity in humans. Here, we demonstrate that CD26 and CD94 define transcriptionally, phenotypically, and functionally distinct Vδ2⁺ T cell subsets. Despite distinct antigen specificities, CD26hiCD94lo Vδ2⁺ cells exhibit substantial similarities...

The domestic ferret (Mustela putorius furo) provides a critical animal model to study human respiratory diseases. However immunological insights are restricted due to a lack of ferret-specific reagents and limited genetic information about ferret B and T cell receptors. Here, variable, diversity and joining genes within the ferret kappa, lambda and...

The full diversity of the circulating human B cell compartment is unknown. Flow cytometry analysis suggests that in addition to naive and memory B cells, there exists a population of CD11c+, CD27- CD21- atypical B cells, that are associated with chronic or recurrent infection and autoimmunity. We used single cell RNA-seq approaches to examine the d...

Protein-based, self-assembling nanoparticles elicit superior immunity compared with soluble protein vaccines, but the immune mechanisms underpinning this effect remain poorly defined. Here, we investigated the immunogenicity of a prototypic ferritin-based nanoparticle displaying influenza hemagglutinin (HA) in mice and macaques. Vaccination of mice...

The rapid global spread of SARS-CoV-2 and resultant mortality and social disruption have highlighted the need to better understand coronavirus immunity to expedite vaccine development efforts. Multiple candidate vaccines, designed to elicit protective neutralising antibodies targeting the viral spike glycoprotein, are rapidly advancing to clinical...

SARS-CoV-2, the pandemic coronavirus that causes COVID-19, has infected millions worldwide, causing unparalleled social and economic disruptions. COVID-19 results in higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive coronavirus immunological responses, induced by circulating human c...

Indigenous Australians are highly susceptible to severe influenza disease during seasonal and pandemic infections. Current antibody-based vaccines targeting humoral immunity are the most effective way to combat influenza infections but show reduced efficacy in Indigenous Australians. The underlying mechanisms are still unknown. We recruited 166 Ind...

Background The Vaxxas high-density microarray patch (HD-MAP) consists of a high density of microprojections coated with vaccine for delivery into the skin. Microarray patches (MAPs) offer the possibility of improved vaccine thermostability as well as the potential to be safer, more acceptable, easier to use, and more cost-effective for the administ...

Background: Seasonal influenza vaccination with a standard trivalent influenza vaccine (TIV) induces a modest, and cross-reactive, Fc functional antibody response in older adults. Recent improvements to influenza vaccines include a quadrivalent influenza vaccine (QIV) and a TIV adjuvanted with the squalene-based oil-in-water emulsion MF59. Method...

A weird way to recognize phosphoantigens In contrast to the well-studied αβ T cells, which recognize peptide antigens presented by major histocompatibility complex (MHC) and MHC-like molecules, how γδ T cells recognize antigens remains largely a mystery. One major class of γδ T cells, designated Vγ9Vδ2 ⁺ , is activated by small, phosphorylated nonp...

Broadly neutralizing Abs targeting the HA stem can provide broad protection against different influenza subtypes, raising the question of how best to elicit such Abs. We have previously demonstrated that vaccination with pandemic live-attenuated influenza vaccine (pLAIV) establishes immune memory for HA head-specific Abs. Here, we determine the ext...

Evaluating the biophysical and functional nature of IgG is key to defining correlates of protection in infectious disease, and autoimmunity research cohorts, as well as vaccine efficacy trials. These studies often require small quantities of IgG to be purified from plasma for downstream analysis with high throughput immunoaffinity formats which elu...

Ferrets are a well‐established model for studying both the pathogenesis and transmission of human respiratory viruses and evaluation of antiviral vaccines. Advanced immunological studies would add substantial value to the ferret models of disease but are hindered by the low number of ferret‐reactive reagents available for flow cytometry and immunoh...

In the version of this article initially published, the labels (50 Å) above the scale bars in Fig. 1b were incorrect. The correct size is 50 nm. The error has been corrected in the HTML and PDF versions of the article.