Vaccine
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Observational Study
Vaccine-associated reduction in symptom severity among patients with influenza A/H3N2 disease.
The moderate level of protection conferred by influenza vaccines is well-known, but the vaccine's ability to attenuate symptom severity among vaccinated individuals (i.e., vaccine failures) has not been established. ⋯ Among patients with A/H3N2 infection, receipt of seasonal influenza vaccine was associated with reduced symptom severity. Patient-centered discussion about the benefits of influenza vaccination should be expanded to include the possibility that the vaccine could attenuate symptoms.
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Estimates of WHO and UNICEF vaccination coverage may provide little insight into the extent to which vaccinations are administered on time. Yet, lack of adherence to the recommended age to receive a specific vaccination may have detrimental health consequences. For example, delays in receiving vaccination will prolong the risk of lack of protection, often when disease risk is highest, such as during early infancy. We estimated the reported age at vaccination, and vaccine coverage at different ages in children from five sub-Saharan African countries. ⋯ In the context of new vaccine introduction, age of children at vaccination should be monitored to interpret data on vaccine-preventable disease burden, vaccine effectiveness, and vaccine safety, and to adapt targeted interventions and messages.
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Targeting immune checkpoint receptors has emerged as an effective strategy to induce immune-mediated cancer regression in the subset of patients who have significant pre-existing anti-tumor immunity. For the remainder, effective anti tumor responses may require vaccination. Radiotherapy, traditionally used to achieve local tumor control, has acquired a new role, that of a partner for immunotherapy. ⋯ Newly generated anti-tumor immune responses have been demonstrated post-radiation in both murine models and occasional patients, supporting the hypothesis that the irradiated tumor can become an in situ vaccine. It is in this role, that radiation can be applied to induce anti-tumor T cells in lymphocyte-poor tumors, and possibly benefit patients who would otherwise fail to respond to immune checkpoint inhibitors. This review summarizes preclinical and clinical data demonstrating that radiation acts in concert with antibodies targeting the immune checkpoint cytotoxic T-lymphocyte antigen-4 (CTLA-4), to induce therapeutically effective anti-tumor T cell responses in tumors otherwise non responsive to anti-CTLA-4 therapy.
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Sanofi Pasteur has developed a recombinant, live-attenuated, tetravalent dengue vaccine (CYD-TDV) that is in late-stage development. The present review summarizes the different steps in the development of this dengue vaccine, with a particular focus on the clinical data from three efficacy trials, which includes one proof-of-concept phase IIb (NCT00842530) and two pivotal phase III efficacy trials (NCT01373281 and NCT01374516). Earlier studies showed that the CYD-TDV candidate had a satisfactory safety profile and was immunogenic across the four vaccine serotypes in both in vitro and in vivo preclinical tests, as well as in initial phase I to phase II clinical trials in both flavivirus-naïve and seropositive individuals. ⋯ The end of the active phases in these studies completes more than a decade of development of CYD-TDV, but considerable activities and efforts remain to address outstanding scientific, clinical, and immunological questions, while preparing for the introduction and use of CYD-TDV. Additional safety observations were recently reported from the first complete year of hospital phase longer term surveillance for two phase 3 studies and the first and second completed years for one phase 2b study, demonstrating the optimal age for intervention from 9 years. Dengue is a complex disease, and both short-term and long-term safety and efficacy will continue to be addressed by ongoing long-term follow-up and future post-licensure studies.