Optimising dengue pre-vaccination screening

Wilder‐Smith, Annelies; Peeling, Rosanna W.

doi:10.1016/s1473-3099(20)30722-2

Cited by 9 publications

(5 citation statements)

References 9 publications

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“…Collectively, these studies outline the importance of an early identification of the causative agent of a suspected arboviral case and the need for discerning naïve from experienced flavivirus individuals due to their relevance in a prompt case management and for vaccination strategies (16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Dynamics of the Magnitude, Breadth and Depth of the Antibody Response at Epitope Level Following Dengue Infection

et al. 2021

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Dengue is a major public health problem in tropical and sub-tropical regions worldwide. Since the Zika epidemic and the increased co-circulation of other arboviruses, the serology-based diagnosis of dengue has become more problematic due to the high antigenic resemblance, especially among the flavivirus family. Therefore, a more comprehensive understanding of the diversity, specificity and temporal evolution of the antibody response following dengue infection is needed. In order to close this knowledge gap, we used a high-density peptide microarray of 9,072 linear peptides covering the entire proteome diversity of dengue, Zika, yellow fever and chikungunya viruses. The IgM and IgG antibody responses were measured against the designed microarray in symptomatic dengue infected individuals from an arbovirus endemic area in Peru and in overseas travelers returning to Belgium, as representatives of multiple-exposed and primary infections, respectively. Serum samples were collected longitudinally across four time points over the period of six months in Peru and over two time points in travelers. We show that epitopes eliciting the strongest flavivirus cross-reactive antibodies, in both primary and secondary infections were concentrated in the capsid, E, NS1, NS3 and NS5 proteins. The IgG antibody responses against NS1 and NS3 followed a rise-and-fall pattern, with peak titers between two to four weeks after onset of illness. The response to the E and NS5 proteins increased rapidly in the acute phase and was maintained at stable levels until at least 6 months after illness. A more scattered IgM antibody reactivity across the viral proteome was observed in the acute phase of the disease and that persisted through the 6-month window. The magnitude, breadth (i.e. number of unique epitopes targeted) and depth (i.e. number of epitope variants recognized) of the IgG response was higher in secondary infections compared to primary infections. For IgM antibodies, the magnitude of the response was higher in primary infected individuals whereas the breadth and depth of the response was lower in this group compared with the endemic subjects. Finally, through this arboviral proteome-wide epitope mapping, we were able to identify IgM and IgG dengue-specific epitopes which can be useful serological markers for dengue diagnosis and serostatus determination.

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Section: Introductionmentioning

confidence: 99%

Dynamics of the Magnitude, Breadth and Depth of the Antibody Response at Epitope Level Following Dengue Infection

et al. 2021

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“…This is to ensure dengue-naïve recipients are not primed for a subsequent severe secondary infection by vaccination [ 45 , 46 ]. However, current screening methods are unable to distinguish those with one or multiple previous infection(s) [ 47 ]. Consequently, numerous individuals could be targeted, at cost, for vaccination yet would not benefit from the protection as they may have experienced multiple dengue infections beforehand.…”

Section: Discussionmentioning

confidence: 99%

Combining rapid diagnostic tests to estimate primary and post-primary dengue immune status at the point of care

Biggs

Ashall

et al. 2022

PLoS Negl Trop Dis

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Background Characterising dengue virus (DENV) infection history at the point of care is challenging as it relies on intensive laboratory techniques. We investigated how combining different rapid diagnostic tests (RDTs) can be used to accurately determine the primary and post-primary DENV immune status of reporting patients during diagnosis. Methods and findings Serum from cross-sectional surveys of acute suspected dengue patients in Indonesia (N:200) and Vietnam (N: 1,217) were assayed using dengue laboratory assays and RDTs. Using logistic regression modelling, we determined the probability of being DENV NS1, IgM and IgG RDT positive according to corresponding laboratory viremia, IgM and IgG ELISA metrics. Laboratory test thresholds for RDT positivity/negativity were calculated using Youden’s J index and were utilized to estimate the RDT outcomes in patients from the Philippines, where only data for viremia, IgM and IgG were available (N:28,326). Lastly, the probabilities of being primary or post-primary according to every outcome using all RDTs, by day of fever, were calculated. Combining NS1, IgM and IgG RDTs captured 94.6% (52/55) and 95.4% (104/109) of laboratory-confirmed primary and post-primary DENV cases, respectively, during the first 5 days of fever. Laboratory test predicted, and actual, RDT outcomes had high agreement (79.5% (159/200)). Among patients from the Philippines, different combinations of estimated RDT outcomes were indicative of post-primary and primary immune status. Overall, IgG RDT positive results were confirmatory of post-primary infections. In contrast, IgG RDT negative results were suggestive of both primary and post-primary infections on days 1–2 of fever, yet were confirmatory of primary infections on days 3–5 of fever. Conclusion We demonstrate how the primary and post-primary DENV immune status of reporting patients can be estimated at the point of care by combining NS1, IgM and IgG RDTs and considering the days since symptoms onset. This framework has the potential to strengthen surveillance operations and dengue prognosis, particularly in low resource settings.

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“…Cross-reactivity to other flaviviruses was low. The final choice of RDTs in each country will depend on the performance of the RDT, dengue seroprevalence in the target population, tolerance of risk, and cost-effectiveness [59]. New data have emerged that support the shortening of the primary schedule from a three-dose to two-dose schedule, extending the age range below 9-6 years of age, and expanding the indication from endemic populations to also include travellers to endemic areas [60].…”

Section: Tetravalent Live-attenuated Recombinant Dengue Vaccine (Cyd-...mentioning

confidence: 99%

Dengue vaccine development: challenges and prospects

Wilder‐Smith

2022

Current Opinion in Infectious Diseases

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Purpose of reviewDengue vaccine development is a high public health priority. To date, no dengue vaccine is in widespread use. Here we review the challenges in dengue development and the latest results for the second-generation dengue vaccines.Recent findingsThe biggest hurdle is the immunological interaction between the four antigenically distinct dengue serotypes. The advantages of second-generation dengue vaccines are the inclusion of nonstructural proteins of the dengue backbone and a more convenient dosing with reduced numbers of doses needed.SummaryAlthough dengue-primed individuals can already benefit from vaccination with the first licensed dengue vaccine CYD-TDV, the public health need for the dengue-naive population has not yet been met. The urgent need remains to identify correlates of both protection and enhancement; until such correlates have been identified, all second-generation dengue vaccines still need to go through full phase 3 trials. The 5-year efficacy and safety data for both second-generation dengue vaccines are imminent.

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Optimising dengue pre-vaccination screening

Cited by 9 publications

References 9 publications

Dynamics of the Magnitude, Breadth and Depth of the Antibody Response at Epitope Level Following Dengue Infection

Dynamics of the Magnitude, Breadth and Depth of the Antibody Response at Epitope Level Following Dengue Infection

Combining rapid diagnostic tests to estimate primary and post-primary dengue immune status at the point of care

Dengue vaccine development: challenges and prospects

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