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A Multiplex Serological Assay for the Detection of Antibody Responses to Arboviruses

Arthropod borne viruses (arboviruses) are a group of mosquito-borne pathogens that are globally distributed. Since the 2016 outbreak of Zika virus (ZIKV) ...

Institut Pasteur, Université Paris-Cité, INSERM U1347

In malaria endemic populations, complex patterns of Plasmodium vivax and Plasmodium falciparum blood-stage infection dynamics may be observed. Genotyping samples from longitudinal cohort studies for merozoite surface protein (msp) variants increases the information available in the data, allowing multiple infecting parasite clones in a single individual to be identified. msp genotyped samples from two longitudinal cohorts in Papua New Guinea (PNG) and Thailand were analysed using a statistical model where the times of acquisition and clearance of each clone in every individual were estimated using a process of data augmentation.

Plasmodium vivax and Plasmodium falciparum infection dynamics: re-infections, recrudescences and relapses.

Plasmodium vivax poses unique challenges for malaria control and elimination, notably the potential for relapses to maintain transmission in the face of drug-based treatment and vector control strategies. We developed an individual-based mathematical model of P. vivax transmission calibrated to epidemiological data from Papua New Guinea (PNG). In many settings in PNG, increasing bed net coverage is predicted to reduce transmission to less than 0.1% prevalence by light microscopy, however there is substantial risk of rebounds in transmission if interventions are removed prematurely. In several high transmission settings, model simulations predict that combinations of existing interventions are not sufficient to interrupt P. vivax transmission. This analysis highlights the potential options for the future of P. vivax control: maintaining existing public health gains by keeping transmission suppressed through indefinite distribution of interventions; or continued development of strategies based on existing and new interventions to push for further reduction and towards elimination.

Mathematical modelling of the impact of expanding levels of malaria control interventions on Plasmodium vivax.

A meningococcal group A conjugate vaccine, PsA-TT (also known as MenAfriVac), was developed with the support of the Meningitis Vaccine Project. Around 280 million individuals aged 1-29 years have been immunised across the African meningitis belt. We analysed the kinetics of vaccine-induced antibody response and assessed the possible implications for duration of protection.

Antibody kinetics following vaccination with MenAfriVac: an analysis of serological data from randomised trials.

As malaria endemic countries strive towards elimination, intensified spatial heterogeneities of local transmission could undermine the effectiveness of traditional intervention policy.

The top 1%: quantifying the unequal distribution of malaria in Brazil.

Children are underrepresented in the COVID-19 pandemic and often experience milder disease than adolescents and adults. Reduced severity is possibly due to recent and more frequent seasonal human coronaviruses (HCoV) infections. We assessed the seroprevalence of SARS-CoV-2 and seasonal HCoV specific antibodies in a large cohort in north-eastern France.

Humoral immunity to SARS-CoV-2 and seasonal coronaviruses in children and adults in north-eastern France.

Over the last decades, the number of malaria cases has drastically reduced in Cambodia. As the overall prevalence of malaria in Cambodia declines, residual malaria transmission becomes increasingly fragmented over smaller remote regions. The aim of this study was to get an insight into the burden and epidemiological parameters of Plasmodium infections on the forest-fringe of Cambodia.

Using serological diagnostics to characterize remaining high-incidence pockets of malaria in forest-fringe Cambodia.

Plasmodium vivax forms dormant liver stages (hypnozoites) that can reactivate weeks to months after primary infection. Radical cure requires a combination of antimalarial drugs to kill both the blood-stage and liver-stage parasites. Hypnozoiticidal efficacy of the liver-stage drugs primaquine and tafenoquine cannot be estimated directly because hypnozoites are undetectable. We aimed to estimate hypnozoiticidal efficacy from clinical trial data, and quantify the community-level impact of implementing case management with radical cure.

Quantifying Plasmodium vivax radical cure efficacy: a modelling study integrating clinical trial data and transmission dynamics.

SARS-CoV-2 remains a significant health threat due to its high infection and mutation rates. The emergence of new variants of concern poses challenges as they can lead to immune escape mutations, potentially reducing the efficacy of vaccines and antibody therapeutics. The receptor binding domain (RBD) of SARS-CoV-2 is particularly noteworthy as it is both the most rapidly evolving domain and the principal target of neutralizing antibodies. As an alternative to time-consuming and expensive neutralization assays, we have developed a bead-based multiplex surrogate virus neutralization test based on ACE2-RBD binding inhibition. We demonstrated how our high-throughput assay allows us to simultaneously assess anti-RBD neutralizing antibodies levels against multiple SARS-CoV-2 variants, providing data that is consistent with the gold-standard live virus neutralization assay. The utility of this assay was demonstrated by applying it to a large French population cohort to demonstrate that hybrid immunity (generated by a combination of vaccination and infection) is associated with protection against infection with the Omicron BA.1 and BA.2 lineages of SARS-COV-2.

Multiplex ACE2-RBD binding inhibition assay: An integrated tool for assessing neutralizing antibodies to SARS-CoV-2 variants and protection against breakthrough infections.

The precise diagnosis of a prior COVID-19 infection remains challenging. This study aimed to evaluate the efficacy of T-SPOT assays for diagnosing prior SARS-CoV-2 infections by using frozen peripheral blood mononuclear cells (PBMCs) combined with antibody tests.

Improving the diagnostic performance for prior COVID-19 with T-SPOT, an interferon-gamma release assay.

Serological assays are key tools in infectious disease surveillance, enabling detection of past infections by measuring antibody responses. Determining appropriate sero-positivity cut-offs, thresholds distinguishing between positive and negative antibody responses, remains a critical methodological challenge.

Article	Year
Plasmodium vivax and Plasmodium falciparum infection dynamics: re-infections, recrudescences and relapses. Malaria journal\| PubMed ID: 29665803	2018
Mathematical modelling of the impact of expanding levels of malaria control interventions on Plasmodium vivax. Nature communications\| PubMed ID: 30120250	2018
Antibody kinetics following vaccination with MenAfriVac: an analysis of serological data from randomised trials. The Lancet. Infectious diseases\| PubMed ID: 30745277	2019
The top 1%: quantifying the unequal distribution of malaria in Brazil. Malaria journal\| PubMed ID: 33579298	2021
Humoral immunity to SARS-CoV-2 and seasonal coronaviruses in children and adults in north-eastern France. EBioMedicine\| PubMed ID: 34304047	2021
Using serological diagnostics to characterize remaining high-incidence pockets of malaria in forest-fringe Cambodia. Malaria journal\| PubMed ID: 38360625	2024
Quantifying Plasmodium vivax radical cure efficacy: a modelling study integrating clinical trial data and transmission dynamics. The Lancet. Infectious diseases\| PubMed ID: 39818221	2025
Multiplex ACE2-RBD binding inhibition assay: An integrated tool for assessing neutralizing antibodies to SARS-CoV-2 variants and protection against breakthrough infections. Journal of immunological methods\| PubMed ID: 40447072	2025
Improving the diagnostic performance for prior COVID-19 with T-SPOT, an interferon-gamma release assay. Frontiers in microbiology\| PubMed ID: 41070127	2025
Whose line is it anyway? Defining sero-positivity cut-offs for infectious disease surveillance. The Journal of infectious diseases\| PubMed ID: 41108092	2025

Michael White

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