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Dengue is a rapidly emerging, mosquito-borne viral infection, with an estimated 400 million infections occurring annually. To gain insight into dengue immunity, we characterized 145 human monoclonal antibodies (mAbs) and identified a previously unknown epitope, the envelope dimer epitope (EDE), that bridges two envelope protein subunits that make up the 90 repeating dimers on the mature virion. The mAbs to EDE were broadly reactive across the dengue serocomplex and fully neutralized virus produced in either insect cells or primary human cells, with 50% neutralization in the low picomolar range. Our results provide a path to a subunit vaccine against dengue virus and have implications for the design and monitoring of future vaccine trials in which the induction of antibody to the EDE should be prioritized.

Serologic testing remains crucial for Zika virus diagnosis. We found that urea wash in a Zika virus nonstructural protein 1 IgG ELISA distinguishes secondary dengue virus infection from Zika virus infection with previous dengue (sensitivity 87.5%, specificity 93.8%). This test will aid serodiagnosis, serosurveillance, and monitoring of Zika complications in dengue-endemic regions. [ABSTRACT FROM AUTHOR]

Humans who experience a primary dengue virus (DENV) infection develop antibodies that preferentially neutralize the homologous serotype responsible for infection. Affected individuals also generate cross-reactive antibodies against heterologous DENV serotypes, which are non-neutralizing. Dengue cross-reactive, non-neutralizing antibodies can enhance infection of Fc receptor bearing cells and, potentially, exacerbate disease. The actual binding sites of human antibody on the DENV particle are not well defined. We characterized the specificity and neutralization potency of polyclonal serum antibodies and memory B-cell derived monoclonal antibodies (hMAbs) from 2 individuals exposed to primary DENV infections. Most DENV-specific hMAbs were serotype cross-reactive and weakly neutralizing. Moreover, many hMAbs bound to the viral pre-membrane protein and other sites on the virus that were not preserved when the viral envelope protein was produced as a soluble, recombinant antigen (rE protein). Nonetheless, by modifying the screening procedure to detect rare antibodies that bound to rE, we were able to isolate and map human antibodies that strongly neutralized the homologous serotype of DENV. Our MAbs results indicate that, in these two individuals exposed to primary DENV infections, a small fraction of the total antibody response was responsible for virus neutralization. [ABSTRACT FROM AUTHOR]

Although mRNA-based COVID-19 vaccines reduce the risk of severe disease, hospitalization and death, vaccine effectiveness (VE) against infection and disease from variants of concern (VOC) wanes over time. Neutralizing antibodies (NAb) are surrogates of protection and are enhanced by a booster dose, but their kinetics and durability remain understudied. Current recommendation of a booster dose does not consider the existing NAb in each individual. Here, we investigated 50% neutralization (NT 50 ) titers against VOC among COVID-19-naive participants receiving the Moderna ( n  = 26) or Pfizer ( n  = 25) vaccine for up to 7 months following the second dose, and determined their half-lives. We found that the time it took for NT 50 titers to decline to 24, equivalent to 50% inhibitory dilution of 10 international units/mL, was longer in the Moderna (325/324/235/274 days for the D614G/alpha/beta/delta variants) group than in the Pfizer (253/252/174/226 days) group, which may account for the slower decline in VE of the Moderna vaccine observed in real-world settings and supports our hypothesis that measuring the NT 50 titers against VOC, together with information on NAb half-lives, can be used to dictate the time of booster vaccination. Our study provides a framework to determine the optimal time of a booster dose against VOC at the individual level. In response to future VOC with high morbidity and mortality, a quick evaluation of NAb half-lives using longitudinal serum samples from clinical trials or research programs of different primary-series vaccinations and/or one or two boosters could provide references for determining the time of booster in different individuals. IMPORTANCE Despite improved understanding of the biology of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the evolutionary trajectory of the virus is uncertain, and the concern of future antigenically distinct variants remains. Current recommendations for a COVID-19 vaccine booster dose are primarily based on neutralization capacity, effectiveness against circulating variants of concern (VOC), and other host factors. We hypothesized that measuring neutralizing antibody titers against SARS-CoV-2 VOC together with half-life information can be used to dictate the time of booster vaccination. Through detailed analysis of neutralizing antibodies against VOC among COVID-19-naive vaccinees receiving either of two mRNA vaccines, we found that the time it took for 50% neutralization titers to decline to a reference level of protection was longer in the Moderna than in the Pfizer group, which supports our hypothesis. In response to future VOC with potentially high morbidity and mortality, our proof-of-concept study provides a framework to determine the optimal time of a booster dose at the individual level., Competing Interests: The authors declare no conflict of interest.

The four serotypes of dengue virus (DENV), belonging to the genus Flavivirus in the family Flaviviridae, are the leading cause of arboviral diseases in humans. The clinical presentations range from dengue fever to dengue hemorrhagic fever and dengue shock syndrome. Despite decades of efforts on developing intervention strategies against DENV, there is no licensed antiviral, and safe and effective vaccines remain challenging. Similar to other flaviviruses, the assembly of DENV particles occurs in the membranes derived from endoplasmic reticulum; immature virions bud into the lumen followed by maturation in the trans-Golgi and transport through the secretary pathway. A unique feature of flavivirus replication is the production of small and slowly sedimenting subviral particles, known as virus-like particles (VLPs). Co-expression of premembrane (prM) and envelope (E) proteins can generate recombinant VLPs, which are biophysically and antigenically similar to infectious virions and have been employed to study the function of prM and E proteins, assembly, serodiagnostic antigens, and vaccine candidates. Previously, we have developed several assays including sucrose cushion ultracentrifugation, sucrose gradient ultracentrifugation, membrane flotation, subcellular fractionation, and glycosidase digestion assay to exploit the interaction between DENV prM and E proteins, membrane association, subcellular localization, glycosylation pattern, and assembly of VLPs and replicon particles. The information derived from these assays have implications to further our understanding of DENV assembly, replication cycle, intervention strategies, and pathogenesis., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Zika virus (ZIKV) is spread among human populations primarily through the bite of Aedes mosquitoes. While most ZIKV infections are asymptomatic or cause self-limited symptoms, the major concerns are its association with Guillain-Barré Syndrome and fetal microcephaly together with other birth defects, known as congenital Zika syndrome (CZS). This article reviews the confirmed Zika cases in the continental United States (U.S.) and Hawai'i thus far, as well as literature of Zika research relevant to Hawai'i. The first case of CZS within the U.S. was reported in Hawai'i, highlighting the unique position of Hawai'i for emerging and re-emerging infectious diseases. Recent studies of the Zika outbreak in Florida demonstrate the key role of Ae. aegypti mosquito in transmission; continuous and proactive vector surveillance in Hawai'i is warranted. Additionally, an updated interim pregnancy guidance for pregnant women with possible ZIKV exposure was summarized. Due to recent decline of ZIKV transmission in the Americas, the risk of ZIKV importation to Hawai'i has been greatly reduced. However, given the presence of Aedes mosquitoes, climate condition, and status of Hawai'i as a travel destination and foreign import market, public health officials and healthcare providers should remain vigilant for a potential outbreak of mosquito-borne diseases in the future., Competing Interests: None of the authors identify any conflicts of interest.

The four serotypes of dengue virus (DENV) cause the most important and common arthropod-borne viral diseases in humans. There have been three major dengue outbreaks in Hawai'i since 1946. The most recent and largest outbreak occurred on Hawai'i Island in 2015-2016. This article reviews the public health response to dengue outbreaks over the period 2001-2016, as well as scientific literature on dengue outbreaks in Hawai'i. As summarized in the assessment by the Centers for Disease Control and Prevention in 2015, Hawaii's response to the dengue outbreak was timely, appropriate, and well-coordinated. All facets of a public health response to the outbreak were adequately addressed, but communications and medical entomologic capacities could be improved. The observations of Aedes aegypti on Hawai'i Island and of its co-localization with confirmed human cases highlight the importance of continuous vector surveillance and entomologic research. In-depth studies on the molecular epidemiology, entomology, and epidemiological investigation would provide new insights into the latest outbreak and into strategies to combat DENV and other arboviruses in the future., Competing Interests: None of the authors identify any conflicts of interest.