Low antibody titers 5 years after vaccination with the CYD-TDV dengue vaccine in both pre-immune and naïve vaccinees

Velumani, Sumathy; Toh, Ying Xiu; Balasingam, Shobana; Archuleta, Sophia; Leo, Yee Sin; Gan, Victor C.; Thein, Tun-Linn; Wilder‐Smith, Annelies; Fink, Katja

doi:10.1080/21645515.2015.1126012

Cited by 20 publications

(10 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While there is a reason to suspect that healthy individuals living in dengue endemic areas might have high or equal level of activated B cells when compare to acute infected patients as a result of previous exposure or an inapparent dengue infection, low levels of plamablasts, plasma cells and activated memory B cells in healthy subjects as observed in this study suggests that dengue exposure must reach a certain threshold in order to induce B cell responses. The natural infection might be required to maintain sufficient levels of antigen exposure as suggested by a study showing that a long term dengue immune memory after vaccination with a chimeric tetravalent DENV vaccine appears relatively low when compare to individuals with a history of natural infection [ 21 ]. As reported earlier, the activated B cells proliferate and differentiate into substantial numbers of antibody-secreting cells to produce soluble antibodies against a wide variety of dengue viral epitopes, some of which specifically recognize and neutralize the dengue virus [ 14 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

B cell subset alteration and the expression of tissue homing molecules in dengue infected patients

et al. 2018

View full text Add to dashboard Cite

BackgroundB cells play an essential role during dengue viral infection. While a major expansion of antibody secreting cells (ASCs) was observed, the importance of these increased frequencies of ASCs remains unclear. The alteration of B cell subsets may result from the expression of tissue specific homing molecules leading to their mobilization and distribution to different target organs during acute dengue viral infection.MethodsIn this study, whole blood samples were obtained from thirty pediatric dengue-infected patients and ten healthy children and then stained with fluorochrome-conjugated monoclonal antibodies against CD3, CD14, CD19, CD20, CD21, CD27, CD38, CD45, CD138 and homing molecules of interest before analyzed by polychromatic flow cytometry. B cell subsets were characterized throughout acute infection period.ResultsData shows that there were no detectable differences in frequencies of resting, activated and tissue memory cells, whereas the frequency of ASCs was significantly increased and associated with the lower frequency of naïve cells. These results were found from patients with both dengue fever and dengue hemorrhagic fever, suggesting that such change or alteration of B cells was not associated with disease severity. Moreover, several homing molecules (e.g., CXCR3 and CCR2) were found in ASCs, indicating that ASCs may distribute to inflamed tissues and various organs.ConclusionsFindings from this study provide insight into B cell subset distribution. Furthermore, organ mobilization according to homing molecule expression on different B cell subsets during the course of dengue viral infection also suggests they are distributed to inflamed tissues and various organs.

show abstract

Section: Discussionmentioning

confidence: 99%

B cell subset alteration and the expression of tissue homing molecules in dengue infected patients

et al. 2018

View full text Add to dashboard Cite

show abstract

“…For binding to recombinant E (rE), MaxiSorp plates were coated with 150 ng of purified rE protein in 100 μl coating buffer at 4°C overnight. rE protein was produced in S2 cells as described previously (17). Antibodies were added at 1 μg/ml, and binding was detected by adding anti-human IgG-horseradish peroxidase (HRP).…”

Section: Methodsmentioning

confidence: 99%

Protective Capacity of the Human Anamnestic Antibody Response during Acute Dengue Virus Infection

Züst

Toh

et al. 2016

J Virol

Self Cite

View full text Add to dashboard Cite

Half of the world's population is exposed to the risk of dengue virus infection. Although a vaccine for dengue virus is now available in a few countries, its reported overall efficacy of about 60% is not ideal. Protective immune correlates following natural dengue virus infection remain undefined, which makes it difficult to predict the efficacy of new vaccines. In this study, we address the protective capacity of dengue virus-specific antibodies that are produced by plasmablasts a few days after natural secondary infection. Among a panel of 18 dengue virus-reactive human monoclonal antibodies, four groups of antibodies were identified based on their binding properties. While antibodies targeting the fusion loop of the glycoprotein of dengue virus dominated the antibody response, two smaller groups of antibodies bound to previously undescribed epitopes in domain II of the E protein. The latter, largely serotype-cross-reactive antibodies, demonstrated increased stability of binding at pH 5. These antibodies possessed weak to moderate neutralization capacity in vitro but were the most efficacious in promoting the survival of infected mice. Our data suggest that the cross-reactive anamnestic antibody response has a protective capacity despite moderate neutralization in vitro and a moderate decrease of viremia in vivo.IMPORTANCE Antibodies can protect from symptomatic dengue virus infection. However, it is not easy to assess which classes of antibodies provide protection because in vitro assays are not always predictive of in vivo protection. During a repeat infection, dengue virus-specific immune memory cells are reactivated and large amounts of antibodies are produced. By studying antibodies cloned from patients with heterologous secondary infection, we tested the protective value of the serotype-cross-reactive “recall” or “anamnestic” response. We found that results from in vitro neutralization assays did not always correlate with the ability of the antibodies to reduce viremia in a mouse model. In addition, a decrease of viremia in mice did not necessarily improve survival. The most protective antibodies were stable at pH 5, suggesting that antibody binding in the endosomes, after the antibody-virus complex is internalized, might be important to block virus spread in the organism.

show abstract

“…The circulating Abs showed low titers 5 years after vaccination, and these Abs from vaccinated individuals had limited in vivo efficacy against DENV2. Although the sample size was too small for definite conclusions, immune memory after vaccination with CYD-TDV appears relatively low ( 105 ).…”

Section: Long-term (Memory) B Cell Responses and Memory Abs During Dementioning

confidence: 99%

The Cellular Bases of Antibody Responses during Dengue Virus Infection

et al. 2016

View full text Add to dashboard Cite

Dengue virus (DENV) is one of the most significant human viral pathogens transmitted by mosquitoes and can cause from an asymptomatic disease to mild undifferentiated fever, classical dengue, and severe dengue. Neutralizing memory antibody (Ab) responses are one of the most important mechanisms that counteract reinfections and are therefore the main aim of vaccination. However, it has also been proposed that in dengue, some of these class-switched (IgG) memory Abs might worsen the disease. Although these memory Abs derive from B cells by T-cell-dependent processes, we know rather little about the (acute, chronic, or memory) B cell responses and the complex cellular mechanisms generating these Abs during DENV infections. This review aims to provide an updated and comprehensive perspective of the B cell responses during DENV infection, starting since the very early events such as the cutaneous DENV entrance and the arrival into draining lymph nodes, to the putative B cell activation, proliferation, and germinal centers (GCs) formation (the source of affinity-matured class-switched memory Abs), till the outcome of GC reactions such as the generation of plasmablasts, Ab-secreting plasma cells, and memory B cells. We discuss topics very poorly explored such as the possibility of B cell infection by DENV or even activation-induced B cell death. The current information about the nature of the Ab responses to DENV is also illustrated.

show abstract

Low antibody titers 5 years after vaccination with the CYD-TDV dengue vaccine in both pre-immune and naïve vaccinees

Cited by 20 publications

References 36 publications

B cell subset alteration and the expression of tissue homing molecules in dengue infected patients

B cell subset alteration and the expression of tissue homing molecules in dengue infected patients

Protective Capacity of the Human Anamnestic Antibody Response during Acute Dengue Virus Infection

The Cellular Bases of Antibody Responses during Dengue Virus Infection

Contact Info

Product

Resources

About