Nanotechnologies are considered to be of growing importance to the vaccine field. Through decoration of immunogens on multivalent nanoparticles, designed nanovaccines can elicit improved humoral immunity. However, significant practical and monetary challenges in large‐scale production of nanovaccines have impeded their widespread clinical translation. Here, an alternative approach is illustrated integrating computational protein modeling and adaptive electroporation‐mediated synthetic DNA delivery, thus enabling direct in vivo production of nanovaccines. DNA‐launched nanoparticles are demonstrated displaying an HIV immunogen spontaneously self‐assembled in vivo. DNA‐launched nanovaccines induce stronger humoral responses than their monomeric counterparts in both mice and guinea pigs, and uniquely elicit CD8+ effector T‐cell immunity as compared to recombinant protein nanovaccines. Improvements in vaccine responses recapitulate when DNA‐launched nanovaccines with alternative scaffolds and decorated antigen are designed and evaluated. Finally, evaluation of functional immune responses induced by DLnanovaccines demonstrates that, in comparison to control mice or mice immunized with DNA‐encoded hemagglutinin monomer, mice immunized with a DNA‐launched hemagglutinin nanoparticle vaccine fully survive a lethal influenza challenge, and have substantially lower viral load, weight loss, and influenza‐induced lung pathology. Additional study of these next‐generation in vivo‐produced nanovaccines may offer advantages for immunization against multiple disease targets.
mAbs are a possible adjunct to vaccination and drugs in treatment of influenza virus infection. However, questions remain whether small animal models accurately predict efficacy in humans. We have established the pig, a large natural host animal for influenza, with many physiological similarities to humans, as a robust model for testing mAbs. We show that a strongly neutralizing mAb (2-12C) against the hemagglutinin head administered prophylactically at 15 mg/kg reduced viral load and lung pathology after pandemic H1N1 influenza challenge. A lower dose of 1 mg/kg of 2-12C or a DNA plasmid-encoded version of 2-12C reduced pathology and viral load in the lungs but not viral shedding in nasal swabs. We propose that the pig influenza model will be useful for testing candidate mAbs and emerging delivery platforms prior to human trials.
This study aimed to evaluate: the coverage of the Food and Nutritional Surveillance System (SISVAN) in the State of Rio Grande do Sul, Brazil, and it Regional Health Offices in 2006; the nutritional status of children 0-10 years of age; and the reliability of data on nutritional status recorded in the system. A cross-sectional descriptive study was conducted with secondary data on 63,320 children. Coverage was defined as the proportion of children younger than 10 years covered by the Family Health Strategy in the State's various municipalities (counties). Height-for-age (H/A) and body mass index for age (BMI/A) were classified according to World Health Organization (WHO) criteria. Agreement between the nutritional classifications recorded in the system and those calculated in this study was evaluated with the weighted kappa coefficient (at 5%). The system's coverage in the State of Rio Grande do Sul was 10.5%. Low height-for-age was found in 7.1% of children and overweight in 8.4%. Agreement between the classifications showed a kappa coefficient of 0.43. The system's coverage and agreement between classifications were both low, and the study showed the coexistence of high overweight and stunting rates in this age group.
Pharmaceuticals and, as such, receive salary and benefits, including ownership of stock and stock options. KM receives grants and consulting fees from Inovio Pharmaceuticals related to DNA vaccine development. DBW has received grant funding, participates in industry collaborations, has received speaking honoraria, and has received fees for consulting, including serving on scientific review committees and board series. Remuneration received by DBW includes direct payments, stock, or stock options, and, in the interest of disclosure, he notes potential conflicts associated with his work with Inovio Pharmaceuticals and possibly others. MCW and DBW have a pending US patent, 62750213.
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