Zika virus (ZIKV) is a flavivirus that is responsible for an unprecedented current epidemic in Brazil and the Americas1,2. ZIKV has been causally associated with fetal microcephaly, intrauterine growth restriction, and other birth defects in both humans3–8 and mice9–11. The rapid development of a safe and effective ZIKV vaccine is a global health priority1,2, but very little is currently known about ZIKV immunology and mechanisms of immune protection. Here we show that a single immunization of a plasmid DNA vaccine or a purified inactivated virus vaccine provides complete protection in susceptible mice against challenge with a ZIKV outbreak strain from northeast Brazil. This ZIKV strain has recently been shown to cross the placenta and to induce fetal microcephaly and other congenital malformations in mice11. We produced DNA vaccines expressing full-length ZIKV pre-membrane and envelope (prM-Env) as well as a series of deletion mutants. The full-length prM-Env DNA vaccine, but not the deletion mutants, afforded complete protection against ZIKV as measured by absence of detectable viremia following challenge, and protective efficacy correlated with Env-specific antibody titers. Adoptive transfer of purified IgG from vaccinated mice conferred passive protection, and CD4 and CD8 T lymphocyte depletion in vaccinated mice did not abrogate protective efficacy. These data demonstrate that protection against ZIKV challenge can be achieved by single-shot subunit and inactivated virus vaccines in mice and that Env-specific antibody titers represent key immunologic correlates of protection. Our findings suggest that the development of a ZIKV vaccine for humans will likely be readily achievable.

Zika virus (ZIKV) is responsible for a major ongoing epidemic in the Americas and has been causally associated with fetal microcephaly. The development of a safe and effective ZIKV vaccine is therefore an urgent global health priority. Here we demonstrate that three different vaccine platforms protect against ZIKV challenge in rhesus monkeys. A purified inactivated virus vaccine induced ZIKV-specific neutralizing antibodies and completely protected monkeys against ZIKV strains from both Brazil and Puerto Rico. Purified immunoglobulin from vaccinated monkeys conferred passive protection in adoptive transfer studies. A plasmid DNA vaccine and a single-shot recombinant rhesus adenovirus serotype 52 vector expressing ZIKV prM-Env also elicited neutralizing antibodies and completely protected monkeys against ZIKV challenge. These data support the rapid clinical development of ZIKV vaccines for humans.

Zika virus (ZIKV) was identified as a cause of congenital disease during an explosive outbreak in the Americas and Caribbean in 2015. Because of the ongoing fetal risk from endemic disease and travel-related exposures, a vaccine to prevent viremia in women of child-bearing age and their partners is imperative. Vaccination with DNA expressing the prM and E proteins of ZIKV was immunogenic in mice and nonhuman primates, and protection against viremia after ZIKV challenge correlated with serum neutralizing activity. These data not only indicate DNA vaccination could be a successful approach to protect against ZIKV infection, but also suggest a protective threshold of vaccine-induced neutralizing activity that will prevent viremia following acute infection.

BackgroundTransmission of dengue viruses (DENV), the leading cause of arboviral disease worldwide, is known to vary through time and space, likely owing to a combination of factors related to the human host, virus, mosquito vector, and environment. An improved understanding of variation in transmission patterns is fundamental to conducting surveillance and implementing disease prevention strategies. To test the hypothesis that DENV transmission is spatially and temporally focal, we compared geographic and temporal characteristics within Thai villages where DENV are and are not being actively transmitted.Methods and FindingsCluster investigations were conducted within 100 m of homes where febrile index children with (positive clusters) and without (negative clusters) acute dengue lived during two seasons of peak DENV transmission. Data on human infection and mosquito infection/density were examined to precisely (1) define the spatial and temporal dimensions of DENV transmission, (2) correlate these factors with variation in DENV transmission, and (3) determine the burden of inapparent and symptomatic infections. Among 556 village children enrolled as neighbors of 12 dengue-positive and 22 dengue-negative index cases, all 27 DENV infections (4.9% of enrollees) occurred in positive clusters (p < 0.01; attributable risk [AR] = 10.4 per 100; 95% confidence interval 1–19.8 per 100]. In positive clusters, 12.4% of enrollees became infected in a 15-d period and DENV infections were aggregated centrally near homes of index cases. As only 1 of 217 pairs of serologic specimens tested in positive clusters revealed a recent DENV infection that occurred prior to cluster initiation, we attribute the observed DENV transmission subsequent to cluster investigation to recent DENV transmission activity. Of the 1,022 female adult Ae. aegypti collected, all eight (0.8%) dengue-infected mosquitoes came from houses in positive clusters; none from control clusters or schools. Distinguishing features between positive and negative clusters were greater availability of piped water in negative clusters (p < 0.01) and greater number of Ae. aegypti pupae per person in positive clusters (p = 0.04). During primarily DENV-4 transmission seasons, the ratio of inapparent to symptomatic infections was nearly 1:1 among child enrollees. Study limitations included inability to sample all children and mosquitoes within each cluster and our reliance on serologic rather than virologic evidence of interval infections in enrollees given restrictions on the frequency of blood collections in children.ConclusionsOur data reveal the remarkably focal nature of DENV transmission within a hyperendemic rural area of Thailand. These data suggest that active school-based dengue case detection prompting local spraying could contain recent virus introductions and reduce the longitudinal risk of virus spread within rural areas. Our results should prompt future cluster studies to explore how host immune and behavioral aspects may impact DENV transmission and prevention s...

As with many pathogens, most dengue infections are subclinical and therefore unobserved1. Coupled with limited understanding of the dynamical behavior of potential serological markers of infection, this observational problem has wide-ranging implications, including hampering our understanding of individual- and population-level correlates of infection and disease risk and how they change over time, assay interpretation and cohort design. We develop a framework that simultaneously characterizes antibody dynamics and identifies subclinical infections via Bayesian augmentation from detailed cohort data (3,451 individuals with blood draws every 91 days, 143,548 hemagglutination inhibition assay titer measurements)2,3. We identify 1,149 infections (95% CI: 1,135–1,163) that were not detected by active surveillance and estimate that 65% of infections are subclinical. Post infection, individuals develop a stable setpoint antibody load after 1y that places them within or outside a risk window. Individuals with pre-existing titers of ≤1:40 develop hemorrhagic fever 7.4 (95% CI: 2.5–8.2) times as often as naïve individuals compared to 0.0 times for individuals with titers >1:40 (95% CI: 0.0–1.3). PRNT titers ≤1:100 were similarly associated with severe disease. Across the population, variability in the force of infection results in large-scale temporal changes in infection and disease risk that correlate poorly with age.

Please cite this paper as: Simmerman et al. (2011) Findings from a household randomized controlled trial of hand washing and face masks to reduce influenza transmission in Bangkok, Thailand. Influenza and Other Respiratory Viruses 5(4), 256–267 Background  Evidence is needed on the effectiveness of non‐pharmaceutical interventions (NPIs) to reduce influenza transmission. Methodology  We studied NPIs in households with a febrile, influenza‐positive child. Households were randomized to control, hand washing (HW), or hand washing plus paper surgical face masks (HW + FM) arms. Study nurses conducted home visits within 24 hours of enrollment and on days 3, 7, and 21. Respiratory swabs and serum were collected from all household members and tested for influenza by RT‐PCR or serology. Principal Findings  Between April 2008 and August 2009, 991 (16·5%) of 5995 pediatric influenza‐like illness patients tested influenza positive. Four hundred and forty‐two index children with 1147 household members were enrolled, and 221 (50·0%) were aged <6 years. Three hundred and ninety‐seven (89·8%) households reported that the index patient slept in the parents’ bedroom. The secondary attack rate was 21·5%, and 56/345 (16·3%; 95% CI 12·4–20·2%) secondary cases were asymptomatic. Hand‐washing subjects reported 4·7 washing episodes/day, compared to 4·9 times/day in the HW + FM arm and 3·9 times/day in controls (P = 0·001). The odds ratios (ORs) for secondary influenza infection were not significantly different in the HW arm (OR = 1·20; 95% CI 0·76–1·88; P‐0.442), or the HW + FM arm (OR = 1·16; 95% CI .0·74–1·82; P = 0.525). Conclusions  Influenza transmission was not reduced by interventions to promote hand washing and face mask use. This may be attributable to transmission that occurred before the intervention, poor facemask compliance, little difference in hand‐washing frequency between study groups, and shared sleeping arrangements. A prospective study design and a careful analysis of sociocultural factors could improve future NPI studies.

Analyzing data from Thailand's 72 provinces, Derek Cummings and colleagues find that decreases in birth and death rates can explain the shift in age distribution of dengue hemorrhagic fever.

Immunity to a single dengue virus (DENV) infection does not provide heterologous immunity to subsequent infection. In fact, the greatest risk for dengue hemorrhagic fever (DHF) is with a second DENV serotype exposure. The risk for DHF with a third or fourth dengue infection relative to a first or second exposure is not known. An analysis of our database of children admitted to the Queen Sirikit National Institute of Child Health and Kamphaeng Phet Provincial Hospital with suspected dengue illness revealed that the number of dengue admissions caused by a third or fourth DENV infection was extremely low (0.08-0.8%). Once admitted, the risk for DHF relative to dengue fever was not different for those experiencing third or fourth DENV infections over those experiencing a second DENV infection. We document new dengue serotype infection sequences leading to DHF of 1-4, 2-3, 3-1, and 3-4.