Abstract. Humoral immune response against dengue virus (DENV) is an important component in dengue-endemic transmission. We conducted a cross-sectional nested cohort study to determine the seroprevalence and frequency of neutralizing antibodies against DENV serotypes in two endemic localities in the state of Morelos, Mexico. The cohort participants (N = 1,196) were screened to determine previous exposure to DENV. Overall seroprevalence was 76.6% (95% confidence interval [95% CI] = 73.6-79.2), and prevalence of neutralizing antibodies in the 5-to 9-year-old group was 82.5% (95% CI = 67.2-92.7), 45% (95% CI = 29.3-61.5), and 65% (95% CI = 48.3-79.4) for DENV-1, DENV-2, and DENV-3, respectively. For participants older than 10 years, the observed seroprevalence was above 60% for each serotype, except DENV-4 in the 10-to 25-year-old group (42.9%); 81% of humoral responses were multitypic. The outcomes of our study contribute to understanding the immune component of dengue transmission and provide focal information for the evaluation of vaccine candidates under development.

Sylvatic dengue viruses (DENV) are both evolutionarily and ecologically distinct from human DENV and are maintained in an enzootic transmission cycle. Evidence of sylvatic human infections from West Africa and Southeast Asia suggests that sylvatic DENV come into regular contact with humans. Thus, this potential of emergence into the human transmission cycle could limit the potential for eradicating this cycle with vaccines currently in late stages of development. We assessed the likelihood of sylvatic DENV-4 emergence in the face of natural immunity to current human strains and vaccination with two DENV-4 vaccine candidates. Our data indicate homotypic neutralization of sylvatic and human DENV-4 strains by human primary convalescent and vaccinee sera but limited heterotypic immunity. These results suggest that emergence of sylvatic strains into the human cycle would be limited by homotypic immunity mediated by virus neutralizing antibodies produced by natural infection or vaccination.

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BackgroundDengue is the most important arboviral disease in the world. Seroprevalence has been proposed as a marker of endemicity, however, studies are scarce.MethodsWe conducted a cross-sectional, stratified cluster, random sample study to measure the seroprevalence of antibodies to dengue virus (DENV) in Mexico. The target population was school children ages 6–17 y from 22 endemic states in Mexico, clustered in four regions: Pacific, South-Central, Southeast and Low.ResultsA total of 2134 subjects provided blood samples for immunoglobulin G antibody detection in serum by enzyme-linked immunosorbent assay. Overall, the seroprevalence of antibodies against DENV was 33.5% (95% confidence interval [CI] 27.5 to 40.1). The Southeast had the highest regional seroprevalence, reaching 70.9% (95% CI 60.3 to 79.7). Seroprevalence was higher in older children in the Southeast region: 62.1% (95% CI 46.9 to 75.2) in children 6–8 y and 82.6% (95% CI 73.8 to 88.9) in 13–17 years old (y). However, this was not consistent in all regions. Seroprevalence was associated with dengue incidence.ConclusionsDENV seroprevalence in Mexico was found to be heterogeneous at the country, regional and state levels. Seroprevalence was linked to long-term exposure and did not adequately reflect recent patterns of transmission, suggesting that utilization of a single epidemiological indicator to define endemic regions should be avoided.

The variability in the host immune response directed against dengue virus (DENV) has demonstrated the need to understand the immune response associated with protection in incident infection. The objective was to estimate the association between serostatus and the risk of incident DENV infection. We used a prospective study from 2014 to 2016 in the localities of Axochiapan and Tepalcingo, Morelos, Mexico. We recruited 966 participants, of which, according to their infection history registered were categorized in four groups. To accomplish the objectives of this study, we selected to 400 participants older than 5 years of age were followed for 2.5 years. Blood samples were taken every 6 months to measure serological status and infection by ELISA. In individuals with at least two previous infections the risk of new infection was lower compared to a seronegative group (hazard ratio adjusted 0.49, 95% CI 0.24–0.98), adjusted for age and locality. Therefore, individuals who have been exposed two times or more to a DENV infection have a lower risk of re-infection, thus showing the role of cross-immunity and its association with protection.