ABSTRACT
Background. Benefit of COVID-19 vaccines is limited by need for freezing, high cost, requirement for multiple boosters, and waning immunity. An unmet need for safe and effective vaccines that can be quickly deployed worldwide during a pandemic exists. A barrier to developing scalable low-cost vaccines is the restricted access to vaccine- or adjuvant-formulations due to protection by intellectual property rights. This limits research to understand their mechanism of action and potential applicability towards vulnerable populations or emerging pathogens. Methods. We studied cellular and molecular mechanisms of action of adjuvant formulations developed for global open access in 4 distinct but complementary in vitro platforms that are human, age-specific, and enable the same individual to serve as control and test condition;generating data on adjuvant-induced responses in vitro that predict activity in vivo. Results. Whole blood assay that models magnitude of innate immune activation and identifies cell types activated showed that liposomal co-formulation of MPL +QS-21 activated monocytes and natural killer cells and induced cytokine production;tissue construct assay that models monocyte extravasation and autonomous differentiation into dendritic cells (DC) showed that only MPL+QS-21 co-formulation promoted CD14+ cells towards DC phenotype;monocyte-derived DC (MoDC) assay that interrogates immune activation type showed that MPL+QS-21 co-formulation in lipid nanoparticles promoted MoDC maturation by increasing CD40, CD86, CCR7 and HLA-DR expression and Th1-polarizing cytokine secretion;and dendritic cell-T cell interface assay that assesses potential of formulations to re-activate SARS-CoV-2 Spike antigen-specific T cells showed that only MPL+QS-21 coformulation enhanced activation of antigen-specific CD4+ and CD8+ T cells. Conclusion. Thus, human in vitro modeling provides new insight into the mechanism of action and synergistic effects of MPL+QS-21, and positions us to study them in vulnerable populations to assess potential age-specific application on vaccine development. Precision vaccinology coupled with global access may enable marked public health progress by accelerating, de-risking, and advancing affordable adjuvanted vaccines to the most vulnerable.
ABSTRACT
Due to the global conjuncture caused by SARS-CoV-2 (COVID 19), health centers and providers have been forced to take alternative measures to provide treatments while safeguarding the health of patients and professionals. In the area of Physical Therapy, telerehabilitation has been the chosen method that allows permanent contact with the patient and at the same time satisfies the requirements of social distancing, without interrupting the recovery process. To determine the effectiveness of the physiotherapeutic interventions applied through telerehabilitation to the patients of the Physical Therapy Laboratory of the Technical University of Ambato, is the purpose of the research, during the state of exception provided by the Government of Ecuador for the health emergency SARS-CoV-2. The study was non-experimental and retrospective, with a quali-quantitative approach, the medical records were classified according to age, sex and diagnosis. The SF-12 Health questionnaire and the Visual Analogue Scale (VAS) were applied to the patients;then the comparative statistical analysis between the SF-12 and VAS was performed before and after the treatment period, using the SPSS software. of the 38 initial participants, in 23.7% the pain disappeared completely;On average, the SF-12 score increased by 14 points (initial 29.9 vs final 43.7) while the T test found significant differences, since when examining the initial and final results of the VAS and the SF-12 questionnaire, A value of 0.00 was obtained, the reference being p = 0.05;thus confirming that the affirmative hypothesis is accepted. All participants showed improvement in quality of life and decrease in pain, concluding that physiotherapy through telerehabilitation is an effective alternative method, in situations in which physical contact with the patient must be avoided.