Homotypic antibodies target novel E glycoprotein domains after natural DENV 3 infection/vaccination.

The envelope (E) glycoprotein is the primary target of type-specific (TS) neutralizing antibodies (nAbs) after infection with any of the four distinct dengue virus serotypes (DENV1-4). nAbs can be elicited to distinct structural E domains (EDs) I, II, or III. However, the relative contribution of these domain-specific antibodies is unclear. To identify the primary DENV3 nAb targets in sera after natural infection or vaccination, chimeric DENV1 recombinant encoding DENV3 EDI, EDII, or EDIII were generated. DENV3 EDII is the principal target of TS polyclonal nAb responses and encodes two or more neutralizing epitopes. In contrast, some were individuals vaccinated with a DENV3 monovalent vaccine-elicited serum TS nAbs targeting each ED in a subject-dependent fashion, with an emphasis on EDI and EDIII. Vaccine responses were also sensitive to DENV3 genotypic variation. This DENV1/3 panel allows the measurement of serum ED TS nAbs, revealing differences in TS nAb immunity after natural infection or vaccination.

Identification of Dengue Virus Serotype 3 Specific Antigenic Sites Targeted by Neutralizing Human Antibodies.

The rational design of dengue virus (DENV) vaccines requires a detailed understanding of the molecular basis for antibody-mediated immunity. The durably protective antibody response to DENV after primary infection is serotype specific. However, there is an incomplete understanding of the antigenic determinants for DENV type-specific (TS) antibodies, especially for DENV serotype 3, which has only one well-studied, strongly neutralizing human monoclonal antibody (mAb). Here, we investigated the human B cell response in children after natural DENV infection in the endemic area of Nicaragua and isolated 15 DENV3 TS mAbs recognizing the envelope (E) glycoprotein. Functional epitope mapping of these mAbs and small animal prophylaxis studies revealed a complex landscape with protective epitopes clustering in at least 6-7 antigenic sites. Potently neutralizing TS mAbs recognized sites principally in E glycoprotein domains I and II, and patterns suggest frequent recognition of quaternary structures on the surface of viral particles.

The respiratory microbiota: associations with influenza symptomatology and viral shedding.

PURPOSE: Manifestations of infection and the degree of influenza virus vary. We hypothesized that the nose/throat microbiota modifies the duration of influenza symptoms and viral shedding. Exploring these relationships may help identify additional methods for reducing influenza severity and transmission. METHODS: Using a household transmission study in Nicaragua, we identified secondary cases of influenza virus infection, defined as contacts with detectable virus or a greater than 4-fold change in hemagglutinin inhibition antibody titer. We characterized the nose/throat microbiota of secondary cases before infection and explored whether the duration of symptoms and shedding differed by bacterial community characteristics. RESULTS: Among 124 secondary cases of influenza, higher bacterial community diversity before infection was associated with longer shedding duration (Shannon acceleration factor [AF]: 1.61, 95% confidence interval [CI]: 1.24, 2.10) and earlier time to infection (Shannon AF: 0.72, 95% CI: 0.53, 0.97; Chao1 AF: 0.992, 95% CI: 0.986, 0.998). Neisseria and multiple other oligotypes were significantly associated with symptom and shedding durations and time to infection. CONCLUSIONS: The nose/throat microbiota before influenza virus infection was associated with influenza symptoms and shedding durations. Further studies are needed to determine if the nose/throat microbiota is a viable target for reducing influenza symptoms and transmission.

Diagnostic accuracy of a rapid influenza test for pandemic influenza A H1N1.

BACKGROUND: With the current influenza A H1N1 pandemic (H1N1pdm), it is extremely important that clinicians can quickly and accurately identify influenza cases. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the performance of the QuickVue Influenza A+B rapid test, we conducted a prospective study of the diagnostic accuracy of the QuickVue Influenza A+B test compared to real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for influenza A H1N1pdm in Nicaraguan children aged 2 to 14 years. Rapid test sensitivity and specificity compared to real-time RT-PCR were 64.1% (95% CI 53.5, 73.9) and 98.3% (95.0, 99.6), respectively. Agreement between the two tests was 86.4% (95% CI 81.7, 90.3), and kappa was calculated to be 0.67 (95% CI 0.56, 0.76). Performance of the rapid test varied by day of presentation, with a sensitivity of 41.7% (95% CI 22.1, 63.4) for samples from children presenting on the day of symptom onset and a sensitivity of 72.1% (95% CI 59.9, 82.3) for samples from children presenting one or more days post-symptom onset. CONCLUSIONS/SIGNIFICANCE: We found that the rapid test performed with moderate sensitivity and high specificity. Test performance varied by day of onset, with lower sensitivity on the day of symptom onset.