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1.
Lancet Microbe ; 3(1): e52-e61, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1915217

ABSTRACT

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 protection from infection with SARS-CoV-2 variants. METHODS: In this meta-analysis, we analysed published data from 24 identified studies on in-vitro neutralisation and clinical protection to understand the loss of neutralisation to existing SARS-CoV-2 variants of concern. We integrated the results of this analysis into our existing statistical model relating in-vitro neutralisation to protection (parameterised on data from ancestral virus infection) to estimate vaccine efficacy against SARS-CoV-2 variants. We also analysed data on boosting of vaccine responses and use the model to predict the impact of booster vaccination on protection against SARS-CoV-2 variants. FINDINGS: The neutralising activity against the ancestral SARS-CoV-2 was highly predictive of neutralisation of variants of concern. Decreases in neutralisation titre to the alpha (1·6-fold), beta (8·8-fold), gamma (3·5-fold), and delta (3·9-fold) variants (compared to the ancestral virus) were not significantly different between different vaccines. Neutralisation remained strongly correlated with protection from symptomatic infection with SARS-CoV-2 variants of concern (r S=0·81, p=0·0005) and the existing model remained predictive of vaccine efficacy against variants of concern once decreases in neutralisation to the variants of concern were incorporated. Modelling of predicted vaccine efficacy against variants over time suggested that protection against symptomatic infection might decrease below 50% within the first year after vaccination for some vaccines. Boosting of previously infected individuals with existing vaccines (which target ancestral virus) is predicted to provide a higher degree of protection from infection with variants of concern than primary vaccination schedules alone. INTERPRETATION: In-vitro neutralisation titres remain a correlate of protection from SARS-CoV-2 variants and modelling of the effects of waning immunity predicts a loss of protection to the variants after vaccination. However, booster vaccination with current vaccines should enable higher neutralisation to SARS-CoV-2 variants than is achieved with primary vaccination, which is predicted to provide robust protection from severe infection outcomes with the current SARS-CoV-2 variants of concern, at least in the medium term. FUNDING: The National Health and Medical Research Council (Australia), the Medical Research Future Fund (Australia), and the Victorian Government.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/epidemiology , COVID-19 Vaccines , Humans , SARS-CoV-2/genetics
2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-338387

ABSTRACT

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 infection has been shown to be strongly correlated with neutralising antibody titres, however, this relationship has been is less well described for severe COVID-19. Protection against severe COVID-19 is higher than against symptomatic infection, and also appears relatively preserved over time and against variants. Here we analyse whether neutralising antibody titre remains predictive of protection against severe COVID-19 in the face of waning neutralising antibody levels and emerging variants. Methods: We extracted data from 15 studies reporting on protection against a range of SARS-CoV-2 clinical endpoints ("any infection", "symptomatic infection" and "severe COVID-19"). We then estimated the concurrent neutralising antibody titres using existing parameters on vaccine potency, neutralising antibody decay, and loss of recognition of variants and investigated the relationship between neutralising antibody titre and vaccine effectiveness against severe COVID-19. Findings: Predicted neutralising antibody titres are strongly correlated with vaccine effectiveness against symptomatic and severe COVID-19 (Spearman rho = .94 and 0.63 respectively, p<.001 for both), consistent with previous estimates of the relationship between neutralisation and protection. Indeed 82% (137 of 167) of reported values of protection against severe COVID-19 across a range of vaccines and variants lie within the 95% confidence intervals of the published model. Interpretation: Neutralising antibody titres are predictive of vaccine effectiveness against severe COVID-19 including in realistic scenarios of waning immunity and viral variants. Funding: National Health and Medical Research Council (Australia), Medical Research Future Fund (Australia).

3.
Nat Microbiol ; 7(6): 896-908, 2022 06.
Article in English | MEDLINE | ID: covidwho-1873507

ABSTRACT

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, enabled the rapid isolation and characterization of all major SARS-CoV-2 variants circulating in Australia in 2021. Our platform facilitated viral variant isolation, rapid resolution of variant fitness using nasopharyngeal swabs and ranking of evasion of neutralizing antibodies. In late 2021, variant of concern Omicron (B1.1.529) emerged. Using our platform, we detected and characterized SARS-CoV-2 VOC Omicron. We show that Omicron effectively evades neutralization antibodies and has a different entry route that is TMPRSS2-independent. Our low-cost platform is available to all and can detect all variants of SARS-CoV-2 studied so far, with the main limitation being that our platform still requires appropriate biocontainment.


Subject(s)
COVID-19 , SARS-CoV-2 , Australia , COVID-19/diagnosis , Humans , Pandemics , SARS-CoV-2/genetics
4.
Immunity ; 55(7): 1316-1326.e4, 2022 07 12.
Article in English | MEDLINE | ID: covidwho-1867266

ABSTRACT

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 Omicron breakthrough infection in vaccinated individuals. Early longitudinal sampling revealed the timing and magnitude of recall, with the phenotypic activation of B cells preceding an increase in neutralizing antibody titers. While vaccination of seropositive individuals resulted in robust recall of humoral and T cell immunity, recall of vaccine-elicited responses was delayed and variable in magnitude during breakthrough infections and depended on the infecting variant of concern. While the delayed kinetics of immune recall provides a potential mechanism for the lack of early control of viral replication, the recall of antibodies coincided with viral clearance and likely underpins the protective effects of vaccination against severe COVID-19.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Neutralizing , Antibodies, Viral , Humans , SARS-CoV-2 , Vaccination
5.
Nat Rev Immunol ; 22(6): 387-397, 2022 06.
Article in English | MEDLINE | ID: covidwho-1815552

ABSTRACT

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 there is a widely expressed view that T cell-mediated immunity also plays an important role in vaccine-mediated protection. Here we discuss the role of vaccine-induced T cells in two distinct stages of infection: firstly, in protection from acquisition of symptomatic SARS-CoV-2 infection following exposure; secondly, if infection does occur, the potential for T cells to reduce the risk of developing severe COVID-19. We describe several lines of evidence that argue against a direct impact of vaccine-induced memory T cells in preventing symptomatic SARS-CoV-2 infection. However, the contribution of T cell immunity in reducing the severity of infection, particularly in infection with SARS-CoV-2 variants, remains to be determined. A detailed understanding of the role of T cells in COVID-19 is critical for next-generation vaccine design and development. Here we discuss the challenges in determining a causal relationship between vaccine-induced T cell immunity and protection from COVID-19 and propose an approach to gather the necessary evidence to clarify any role for vaccine-induced T cell memory in protection from severe COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , COVID-19 Vaccines , Humans
6.
Clin Infect Dis ; 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1769230

ABSTRACT

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.

7.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331041

ABSTRACT

Neutralising antibodies are an important correlate of protection from SARS-CoV-2 infection. Multiple studies have investigated the effectiveness of passively administered antibodies (either monoclonal antibodies, convalescent plasma or hyperimmune immunoglobulin) in preventing acquisition of or improving the outcome of infection. Comparing the results between studies is challenging due to different study characteristics including disease stage, trial enrolment and outcome criteria, and different product factors, including administration of polyclonal or monoclonal antibody, and antibody targets and doses. Here we integrate data from 37 randomised controlled trials to investigate how the timing and dose of passive antibodies predicts protection from SARS-CoV-2 infection. We find that both prophylactic and early therapeutic administration (to symptomatic ambulant subjects) have significant efficacy in preventing infection or progression to hospitalisation respectively. However, we find that effectiveness of passive antibody therapy in preventing clinical progression is significantly reduced with administration at later clinical stages (p<0.0001). To compare the dose-response relationship between different treatments, we normalise the administered antibody dose to the predicted neutralisation titre (after dilution) compared to the mean titre observed in early convalescent subjects. We use a logistic model to analyse the dose-response curve of passive antibody administration in preventing progression from symptomatic infection to hospitalisation. We estimate a maximal protection from progression to hospitalisation of 70.2% (95% CI: 62.1 - 78.3%). The dose required to achieve 50% of the maximal effect (EC-50) for prevention of progression to hospitalisation was 0.19-fold (95% CI: 0.087 - 0.395) of the mean early convalescent titre. This suggests that for current monoclonal antibody regimes, doses between 7- and >1000-fold lower than currently used could still achieve around 90% of the current effectiveness (depending on the variant) and allow much more widespread use at lower cost. For convalescent plasma, most current doses are lower than required for high levels of protection. This work provides a framework for the rational design of future passive antibody prophylaxis and treatment strategies for COVID-19.

8.
Nature ; 602(7898): 654-656, 2022 02.
Article in English | MEDLINE | ID: covidwho-1616992

ABSTRACT

The emergence of the SARS-CoV-2 variant of concern Omicron (Pango lineage B.1.1.529), first identified in Botswana and South Africa, may compromise vaccine effectiveness and lead to re-infections1. Here we investigated Omicron escape from neutralization by antibodies from South African individuals vaccinated with Pfizer BNT162b2. We used blood samples taken soon after vaccination from individuals who were vaccinated and previously infected with SARS-CoV-2 or vaccinated with no evidence of previous infection. We isolated and sequence-confirmed live Omicron virus from an infected person and observed that Omicron requires the angiotensin-converting enzyme 2 (ACE2) receptor to infect cells. We compared plasma neutralization of Omicron relative to an ancestral SARS-CoV-2 strain and found that neutralization of ancestral virus was much higher in infected and vaccinated individuals compared with the vaccinated-only participants. However, both groups showed a 22-fold reduction in vaccine-elicited neutralization by the Omicron variant. Participants who were vaccinated and had previously been infected exhibited residual neutralization of Omicron similar to the level of neutralization of the ancestral virus observed in the vaccination-only group. These data support the notion that reasonable protection against Omicron may be maintained using vaccination approaches.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Immune Evasion/immunology , Neutralization Tests , SARS-CoV-2/immunology , Angiotensin-Converting Enzyme 2/metabolism , Animals , Cell Line , Chlorocebus aethiops , Humans , Mutation , SARS-CoV-2/classification , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism
9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296508

ABSTRACT

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 and it eclipsed the other variants of concern (VOC) in its number of Spike polymorphisms, and its ability to compete with and displacement of the dominant VOC Delta. Herein we accessed the impact of Omicron to humoral neutralisation in vaccinated, convalescent cohorts, in concentrated human IgG from thousands of plasma donors and also alongside many clinically used monoclonal antibodies. Overall, we observed a 17 to 22 fold drop in neutralisation titres across all donors that reached a titre to Omicron. Concentrated pooled human IgG from convalescent and vaccinated donors had greater breadth but was still reduced by 16-fold. In all therapeutic antibodies tested, significant neutralization was only observed for Sotrovimab, with other monoclonals unable to neutralize B.1.1.529.

10.
Lancet Microbe ; 3(1): e52-e61, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1517553

ABSTRACT

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 protection from infection with SARS-CoV-2 variants. METHODS: In this meta-analysis, we analysed published data from 24 identified studies on in-vitro neutralisation and clinical protection to understand the loss of neutralisation to existing SARS-CoV-2 variants of concern. We integrated the results of this analysis into our existing statistical model relating in-vitro neutralisation to protection (parameterised on data from ancestral virus infection) to estimate vaccine efficacy against SARS-CoV-2 variants. We also analysed data on boosting of vaccine responses and use the model to predict the impact of booster vaccination on protection against SARS-CoV-2 variants. FINDINGS: The neutralising activity against the ancestral SARS-CoV-2 was highly predictive of neutralisation of variants of concern. Decreases in neutralisation titre to the alpha (1·6-fold), beta (8·8-fold), gamma (3·5-fold), and delta (3·9-fold) variants (compared to the ancestral virus) were not significantly different between different vaccines. Neutralisation remained strongly correlated with protection from symptomatic infection with SARS-CoV-2 variants of concern (r S=0·81, p=0·0005) and the existing model remained predictive of vaccine efficacy against variants of concern once decreases in neutralisation to the variants of concern were incorporated. Modelling of predicted vaccine efficacy against variants over time suggested that protection against symptomatic infection might decrease below 50% within the first year after vaccination for some vaccines. Boosting of previously infected individuals with existing vaccines (which target ancestral virus) is predicted to provide a higher degree of protection from infection with variants of concern than primary vaccination schedules alone. INTERPRETATION: In-vitro neutralisation titres remain a correlate of protection from SARS-CoV-2 variants and modelling of the effects of waning immunity predicts a loss of protection to the variants after vaccination. However, booster vaccination with current vaccines should enable higher neutralisation to SARS-CoV-2 variants than is achieved with primary vaccination, which is predicted to provide robust protection from severe infection outcomes with the current SARS-CoV-2 variants of concern, at least in the medium term. FUNDING: The National Health and Medical Research Council (Australia), the Medical Research Future Fund (Australia), and the Victorian Government.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/epidemiology , COVID-19 Vaccines , Humans , SARS-CoV-2/genetics
11.
Cell Rep ; 37(2): 109822, 2021 10 12.
Article in English | MEDLINE | ID: covidwho-1433046

ABSTRACT

Potent neutralizing monoclonal antibodies are one of the few agents currently available to treat COVID-19. SARS-CoV-2 variants of concern (VOCs) that carry multiple mutations in the viral spike protein can exhibit neutralization resistance, potentially affecting the effectiveness of some antibody-based therapeutics. Here, the generation of a diverse panel of 91 human, neutralizing monoclonal antibodies provides an in-depth structural and phenotypic definition of receptor binding domain (RBD) antigenic sites on the viral spike. These RBD antibodies ameliorate SARS-CoV-2 infection in mice and hamster models in a dose-dependent manner and in proportion to in vitro, neutralizing potency. Assessing the effect of mutations in the spike protein on antibody recognition and neutralization highlights both potent single antibodies and stereotypic classes of antibodies that are unaffected by currently circulating VOCs, such as B.1.351 and P.1. These neutralizing monoclonal antibodies and others that bind analogous epitopes represent potentially useful future anti-SARS-CoV-2 therapeutics.


Subject(s)
Angiotensin-Converting Enzyme 2/immunology , Antibodies, Neutralizing/immunology , SARS-CoV-2/immunology , Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme 2/ultrastructure , Animals , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/therapeutic use , Antibodies, Neutralizing/ultrastructure , Antibodies, Viral/immunology , COVID-19/immunology , Cricetinae , Cryoelectron Microscopy/methods , Epitopes/immunology , Female , Humans , Male , Mice , Mice, Inbred C57BL , Middle Aged , Neutralization Tests , Protein Binding/physiology , Receptors, Virus/metabolism , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
12.
Nat Med ; 27(7): 1205-1211, 2021 07.
Article in English | MEDLINE | ID: covidwho-1232070

ABSTRACT

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 using data from seven current vaccines and from convalescent cohorts. We estimated the neutralization level for 50% protection against detectable SARS-CoV-2 infection to be 20.2% of the mean convalescent level (95% confidence interval (CI) = 14.4-28.4%). The estimated neutralization level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level; 95% CI = 0.7-13%, P = 0.0004). Modeling of the decay of the neutralization titer over the first 250 d after immunization predicts that a significant loss in protection from SARS-CoV-2 infection will occur, although protection from severe disease should be largely retained. Neutralization titers against some SARS-CoV-2 variants of concern are reduced compared with the vaccine strain, and our model predicts the relationship between neutralization and efficacy against viral variants. Here, we show that neutralization level is highly predictive of immune protection, and provide an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , SARS-CoV-2/immunology , COVID-19/immunology , Humans , Logistic Models , Severity of Illness Index
13.
Cell Rep Med ; 2(6): 100296, 2021 06 15.
Article in English | MEDLINE | ID: covidwho-1225428

ABSTRACT

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 coronavirus disease 2019 (COVID-19) is largely unknown. We develop assays to measure Fc-dependent antibody functions against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S)-expressing cells in serial samples from subjects primarily with mild-moderate COVID-19 up to 149 days post-infection. We find that S-specific antibodies capable of engaging Fcγ receptors decay over time, with S-specific antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent phagocytosis (ADP) activity within plasma declining accordingly. Although there is significant decay in ADCC and ADP activity, they remain readily detectable in almost all subjects at the last time point studied (94%) in contrast with neutralization activity (70%). Although it remains unclear the degree to which Fc effector functions contribute to protection against SARS-CoV-2 re-infection, our results indicate that antibodies with Fc effector functions persist longer than neutralizing antibodies.


Subject(s)
Antibodies, Viral/metabolism , COVID-19/immunology , Immunoglobulin Fc Fragments/metabolism , Antibodies, Viral/blood , Antibody-Dependent Cell Cytotoxicity/immunology , COVID-19/pathology , COVID-19/virology , Cell Line, Tumor , Dimerization , Humans , Immunoglobulin Fc Fragments/genetics , Immunoglobulin Fc Fragments/immunology , Kinetics , Neutralization Tests , Phagocytosis , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Severity of Illness Index , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism
14.
Proc Natl Acad Sci U S A ; 118(19)2021 05 11.
Article in English | MEDLINE | ID: covidwho-1203483

ABSTRACT

Neutralizing antibodies are important for immunity against SARS-CoV-2 and as therapeutics for the prevention and treatment of COVID-19. Here, we identified high-affinity nanobodies from alpacas immunized with coronavirus spike and receptor-binding domains (RBD) that disrupted RBD engagement with the human receptor angiotensin-converting enzyme 2 (ACE2) and potently neutralized SARS-CoV-2. Epitope mapping, X-ray crystallography, and cryo-electron microscopy revealed two distinct antigenic sites and showed two neutralizing nanobodies from different epitope classes bound simultaneously to the spike trimer. Nanobody-Fc fusions of the four most potent nanobodies blocked ACE2 engagement with RBD variants present in human populations and potently neutralized both wild-type SARS-CoV-2 and the N501Y D614G variant at concentrations as low as 0.1 nM. Prophylactic administration of either single nanobody-Fc or as mixtures reduced viral loads by up to 104-fold in mice infected with the N501Y D614G SARS-CoV-2 virus. These results suggest a role for nanobody-Fc fusions as prophylactic agents against SARS-CoV-2.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , SARS-CoV-2/immunology , Single-Domain Antibodies , Angiotensin-Converting Enzyme 2/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/pharmacology , Antibodies, Viral/immunology , Antibodies, Viral/pharmacology , COVID-19/drug therapy , COVID-19/immunology , Camelids, New World , Humans , Mice , Single-Domain Antibodies/immunology , Single-Domain Antibodies/pharmacology
15.
Nat Commun ; 12(1): 1162, 2021 02 19.
Article in English | MEDLINE | ID: covidwho-1091489

ABSTRACT

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 serum clonotypes, decay over the first 4 months post-infection. A similar decline in Spike-specific CD4+ and circulating T follicular helper frequencies occurs. By contrast, S-specific IgG+ memory B cells consistently accumulate over time, eventually comprising a substantial fraction of circulating the memory B cell pool. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent participants to 74 days, although there is probably additive protection from B cell and T cell immunity. This study indicates that SARS-CoV-2 immunity after infection might be transiently protective at a population level. Therefore, SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long-term protection.


Subject(s)
Antibodies, Viral/immunology , Antibody Formation , COVID-19/immunology , Immunity, Cellular , Immunologic Memory , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , Humans , Immunoglobulin G/immunology , Longitudinal Studies , Models, Theoretical , Neutralization Tests , T-Lymphocytes, Helper-Inducer/immunology
16.
Nat Rev Immunol ; 20(12): 727-738, 2020 12.
Article in English | MEDLINE | ID: covidwho-899931

ABSTRACT

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 and therapeutic interventions in humans. However, the apparent potency of different interventions can vary considerably between assays and animal models, leading to very different predictions of clinical efficacy. Complete harmonization of experimental methods may be intractable at the current pace of research. However, here we analyse a selection of existing assays for measuring antibody-mediated virus neutralization and animal models of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and provide a framework for comparing results between studies and reconciling observed differences in the effects of interventions. Finally, we propose how we might optimize these assays for better comparison of results from in vitro and animal studies to accelerate progress.


Subject(s)
COVID-19 Serological Testing/methods , COVID-19/immunology , Immunoassay/methods , Animals , COVID-19/drug therapy , COVID-19/prevention & control , Disease Models, Animal , Humans , Neutralization Tests , Pre-Exposure Prophylaxis
17.
Elife ; 92020 08 13.
Article in English | MEDLINE | ID: covidwho-714074

ABSTRACT

As of 1 May 2020, there had been 6808 confirmed cases of COVID-19 in Australia. Of these, 98 had died from the disease. The epidemic had been in decline since mid-March, with 308 cases confirmed nationally since 14 April. This suggests that the collective actions of the Australian public and government authorities in response to COVID-19 were sufficiently early and assiduous to avert a public health crisis - for now. Analysing factors that contribute to individual country experiences of COVID-19, such as the intensity and timing of public health interventions, will assist in the next stage of response planning globally. We describe how the epidemic and public health response unfolded in Australia up to 13 April. We estimate that the effective reproduction number was likely below one in each Australian state since mid-March and forecast that clinical demand would remain below capacity thresholds over the forecast period (from mid-to-late April).


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Australia/epidemiology , COVID-19 , Child , Child, Preschool , Communicable Disease Control/methods , Communicable Disease Control/organization & administration , Communicable Disease Control/statistics & numerical data , Coronavirus Infections/prevention & control , Female , Forecasting , Geography, Medical , Hospitalization/statistics & numerical data , Humans , Infant , Infant, Newborn , Male , Middle Aged , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Public Health , Quarantine , SARS-CoV-2 , Travel , Young Adult
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