V180 / National Institute of Allergy and Infectious Diseases, Merck (MSD) - LARVOL DELTA

Lymph Node Fine Needle Aspirations on Individuals Receiving a Monovalent Live Attenuated Dengue Vaccine (ASTMH 2024) - P1 | "Future work will utilize high-dimensional flow cytometry and single-cell RNA sequencing to evaluate how prior DENV exposure influences the phenotype and kinetics of antigen-specific responses. This work will aid in rational vaccine design."

Clinical • Late-breaking abstract • Anesthesia • Dengue Fever • Infectious Disease • Pain

Phase 1 trial to model primary, secondary, and tertiary dengue infection using a monovalent vaccine (ASTMH 2024) - P1 | "We are conducting a partially blinded phase I vaccine trial (NCT05691530) to examine how natural immunity influences the signs and symptoms, viremia, and immune responses to a dengue vaccine...Ongoing work will evaluate neutrophil and T cell responses, and germinal center changes using sequential fine needle lymph node aspirates. This study will elucidate the immunological factors driving the induction of cross-serotypic protective immunity, inform correlates of protection, and highlight potential therapeutic targets."

P1 data • Dengue Fever • Infectious Disease

Characterization of Aedes aegypti infection with the naturally attenuated DENV-2D30-7169 virus (ASTMH 2024) - "Several dengue virus (DENV) challenge human infection models (CHIMs) have been used to assess the safety and efficacy of dengue vaccines and therapies...Finally, we detected virus in mosquito saliva by PCR and confirmed its infectivity by salivary gland titration in Vero cell. In summary, we show that DENV-2Δ30-7169 can infect and disseminate within Aedes aegypti mosquitoes following intrathoracic inoculation, making this a suitable model to develop a “natural CHIM” using dengue infected mosquitoes."

Dengue Fever • Infectious Disease

Immunity to Non-Dengue Flaviviruses Impacts Dengue Virus Immunoglobulin G Enzyme-Linked Immunosorbent Assay Specificity in Cambodia. (PubMed, J Infect Dis) - P | "Physicians and public health authorities should be alert for West Nile in Cambodia. Immunity to non-dengue flaviviruses can impact dengue surveillance."

Journal • CNS Disorders • Dengue Fever • Infectious Disease

Efficacy and safety of Butantan-DV in participants aged 2-59 years through an extended follow-up: results from a double-blind, randomised, placebo-controlled, phase 3, multicentre trial in Brazil. (PubMed, Lancet Infect Dis) - P3 | "A single dose of Butantan-DV was generally well tolerated and efficacious against symptomatic VCD (caused by DENV-1 and DENV-2) for a mean of 3·7 years. These findings support the continued development of Butantan-DV to prevent dengue disease in children, adolescents, and adults regardless of dengue serostatus."

Journal • P3 data • Dengue Fever

Antibodies to Aedes aegypti D7L salivary proteins as a new serological tool to estimate human exposure to Aedes mosquitoes. (PubMed, Front Immunol) - "The lack of widely available dengue vaccines accentuates the importance of targeted vector control strategies to reduce the dengue burden...The baseline median AeD7L1+2 IgG responses for young children were higher in those who developed asymptomatic versus symptomatic dengue. The IgG response against AeD7L1+2 recombinant proteins is a highly sensitive and Aedes specific marker of human exposure to Aedes bites that can facilitate standardization of future serosurveys and epidemiological studies by its ability to provide a robust estimation of human-mosquito contact in a high-throughput fashion."

Journal • Dengue Fever • Pediatrics

Effect of single-dose, live, attenuated dengue vaccine in children with or without previous dengue on risk of subsequent, virologically confirmed dengue in Cebu, the Philippines: a longitudinal, prospective, population-based cohort study. (PubMed, Lancet Infect Dis) - "The risk of developing virologically confirmed dengue after a single dose of CYD-TDV varied by baseline DENV serostatus. Since the study assessed the effect of only a single dose, the findings cannot inform decisions on vaccination by public health officers. However, the findings have implications for children who receive an incomplete vaccination regimen and these results should prompt more detailed analyses in future trials on dengue vaccines."

Journal • Allergy • Dengue Fever • Immunology • Infectious Disease

Live, Attenuated, Tetravalent Butantan-Dengue Vaccine in Children and Adults. (PubMed, N Engl J Med) - P3 | "A single dose of Butantan-DV prevented symptomatic DENV-1 and DENV-2, regardless of dengue serostatus at baseline, through 2 years of follow-up. (Funded by Instituto Butantan and others; DEN-03-IB ClinicalTrials.gov number, NCT02406729, and WHO ICTRP number, U1111-1168-8679.)."

Journal • Dengue Fever

TV005 dengue vaccine protects against dengue serotype 2 and 3 controlled human infection. (PubMed, J Clin Invest) - P1 | "TV005 is a leading tetravalent dengue vaccine candidate which fully protects against infection with DENV2 and DENV3 in an established controlled human infection model.CLINICAL TRIALS REGISTRATION NUMBERS. NCT02317900 and NCT02873260."

Clinical • Journal • Dengue Fever • Hematological Disorders • Human Immunodeficiency Virus • Infectious Disease • Neutropenia

Antibody Fc correlates of protection against severe dengue disease (ASTMH 2023) - "We found that virolysis of ZIKV virions mediated by samples from DENV-exposed, ZIKV-naïve individuals was most strongly associated with protection, suggesting that 1) anti-DENV antibodies that cross-react with ZIKV and 2) antibodies that target virion-specific epitopes are correlated with protection from severe dengue disease. In sum, our study provides important insights into the biophysical features and effector functions of cross-reactive antibodies that may inform the development of effective dengue vaccines."

Dengue Fever • Hematological Disorders • Infectious Disease • Pediatrics

Impact of dengue virus strain and maturation state on detection of neutralizing antibodies induced by natural infection and vaccination (ASTMH 2023) - "Dengue vaccine developers have relied on standard plaque or focus reduction neutralization tests (PRNT/FRNT) to assess immunogenicity of each of the 4 dengue virus (DENV) serotype components in tetravalent vaccines...Our results demonstrate that DENV NAbs detected using mature, low-passage clinical strains more accurately reflect the serotype responsible for infection compared to the current standard practice. We propose that using mature low passage clinical strains will also lead to more accurate determinations of the immunogenicity and protective potential of each serotype component in tetravalent DENV vaccines in comparison to the current standard."

Dengue Fever • Infectious Disease • FURIN

Safety and durable immunogenicity of the TV005 tetravalent dengue vaccine, across serotypes and age groups, in dengue-endemic Bangladesh: a randomised, controlled trial. (PubMed, Lancet Infect Dis) - P2 | "With 3 years of follow-up, the single-dose tetravalent dengue vaccine, TV005, was well tolerated and immunogenic for all four serotypes in young children to adults, including individuals with no previous dengue exposure."

Journal • Allergy • Dengue Fever • Immunology • Infectious Disease • Musculoskeletal Pain

Previous Dengue Infection among Children in Puerto Rico and Implications for Dengue Vaccine Implementation. (PubMed, Am J Trop Med Hyg) - "The highest force of infection occurred in 2007, 2010, and 2012-2013, with low levels of transmission from 2016 to 2018. A higher proportion of children had evidence of multitypic DENV infection than expected, suggesting high heterogeneity in DENV risk in this setting."

Journal • Dengue Fever • Infectious Disease

Phase 1 trial to model primary, secondary, and tertiary dengue using a monovalent vaccine. (PubMed, BMC Infect Dis) - P1 | "This trial will compare the immune responses after primary, secondary, and tertiary DENV exposure in naturally infected humans living in non-endemic areas. By evaluating dengue vaccines in a new population and modeling the induction of cross-serotypic immunity, this work may inform vaccine evaluation and broaden potential target populations."

Journal • P1 data • Dengue Fever • Infectious Disease

Antibody Fc biophysical features and effector functions are associated with protection from dengue severe disease (ASTMH 2022) - "We found that virolysis of ZIKV virions mediated by plasma/serum from DENV-exposed, ZIKV-naïve individuals was very strongly associated with protection, suggesting that anti-DENV antibodies that cross-react with ZIKV are correlates of protection from severe dengue disease. In sum, we identified protective Fc biophysical features and effector functions of DENV-ZIKV cross-reactive antibodies that may support the design and evaluation of dengue vaccines."

Late-breaking abstract • Dengue Fever • Hematological Disorders • Infectious Disease • Pediatrics

'Mix and Match' vaccination: Is dengue next? (PubMed, Vaccine) - "Heterologous sequential vaccination may be an effective approach for protecting against dengue, as this strategy would mimic the natural route to broad dengue protection and may overcome the imbalances in efficacy of the individual leading live attenuated dengue vaccines...Various heterologous regimens including different combinations and sequences should be trialed to optimize cellular and humoral immunity and the breadth of the response while limiting reactogenicity. A blossoming field dedicated to more accurate correlates of protection and enhancement will help confirm the safety and efficacy of these strategies."

Journal • Review • Dengue Fever • Human Immunodeficiency Virus • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Antibody Fc characteristics and effector functions correlate with protection from symptomatic dengue virus type 3 infection. (PubMed, Sci Transl Med) - "Furthermore, in vitro virological assays using these plasma samples revealed that protection mediated by antibody-dependent complement deposition was associated with both lysis of virions and DENV-infected cells. These data suggest that E- and NS1-specific Fc functions may serve as correlates of protection, which can be potentially applied toward the design and evaluation of dengue vaccines."

Journal • Dengue Fever • Hematological Disorders • Infectious Disease • Pediatrics

The innate immune response following multivalent dengue vaccination and implications for protection against dengue challenge. (PubMed, JCI Insight) - "Understanding the immune response to dengue virus (DENV) is essential for developing a dengue vaccine that is protective against all four DENV serotypes...In response to challenge, white participants elicit a stronger response than black participants. These results may explain why white participants may have a more vigorous DENV immune response than black participants reported in literature."

Journal • Dengue Fever • Immunology • Infectious Disease • CCL4 • IL1R1

Adapting Rapid Diagnostic Tests to Detect Historical Dengue Virus Infections. (PubMed, Front Immunol) - "The only licensed dengue vaccine, Dengvaxia, increases risk of severe dengue when given to individuals without prior dengue virus (DENV) infection but is protective against future disease in those with prior DENV immunity...The Excivion Zika RDT had high specificity (>98%) and sensitivity (>93%) when evaluated quantitatively, suggesting it may be used alongside dengue RDTs to minimize misclassification due to cross-reactivity. Our findings demonstrate the potential of RDTs to be used for dengue pre-vaccination screening to reduce vaccine-induced priming for severe dengue and show how assay design adaptations as well quantitative evaluation can further improve RDTs for this purpose."

Journal • Dengue Fever • Infectious Disease