Biology subjects

de Oliveira, A. C.

Publications and source records attributed to de Oliveira, A. C..

2 recordsLinked to original sources

bioRxiv2021

Immunogenicity of trimetric spike protein associated to Poly(I:C) plus Alum

The SARS-CoV-2 pandemic has had a social and economic impact worldwide, and vaccination is an efficient strategy for diminishing those damages. New adjuvant formulations are required for the high vaccine demands, especially adjuvant formulations that induce a Th1 phenotype. Herein we assess a vaccination strategy using a combination of Alum and polyinosinic:polycytidylic acid (Poly(I:C)) adjuvants plus the SARS-CoV-2 spike protein in a prefusion trimeric conformation by an intradermal (ID) route. We found high levels of IgG anti-spike antibodies in the serum by enzyme linked immunosorbent assay (ELISA) and high neutralizing titers against SARS-CoV-2 in vitro by neutralization assay, after one or two boosts. By evaluating the production of IgG subtypes, as expected, we found that formulations containing Poly(I:C) induced IgG2a whereas Alum did not. The combination of these two adjuvants induced high levels of both IgG1 and IgG2a. In addition, cellular immune responses of CD4+ and CD8+ T cells producing interferon-gamma were equivalent, demonstrating that the Alum + Poly(I:C) combination supported a Th1 profile. Based on the high neutralizing titers, we evaluated B cells in the germinal centers, which are specific for receptor-binding domain (RBD) and spike, and observed that more positive B cells were induced upon the Alum + Poly(I:C) combination. Moreover, these B cells produced antibodies against both RBD and non-RBD sites. We also studied the impact of this vaccination preparation (spike protein with Alum + Poly(I:C)) in the lungs of mice challenged with inactivated SARS-CoV-2 virus. We found a production of IgG, but not IgA, and a reduction in neutrophil recruitment in the bronchoalveolar lavage fluid (BALF) of mice, suggesting that our immunization scheme reduced lung inflammation. Altogether, our data suggest that Alum and Poly(I:C) together is a possible adjuvant combination for vaccines against SARS-CoV-2 by the intradermal route.

immunology↗

bioRxiv2020

Preventive training interferes with mRNA-encoding myosin 7 and collagen I expression during pulmonary arterial hypertension

To gain insight on the impact of preventive exercise during pulmonary arterial hypertension (PAH), we evaluated the gene expression of myosins and gene-encoding proteins associated with the extracellular matrix remodeling of right hypertrophied ventricles. We used 32 male Wistar rats, separated in four groups: Sedentary Control (S; n=8); Control with Training (T; n=8); Sedentary with Pulmonary Arterial Hypertension (SPAH; n=8); and Pulmonary Arterial Hypertension with Training (TPAH; n=8). The rats trained for thirteen weeks on a treadmill. They had two weeks of adaptation training. The PAH was induced by application of monocrotaline 60 mg/kg. Consequential right ventricular dysfunction was observed after the 10th week of training. Rats in the control group received saline application. At the end of the 13th week, echocardiography analysis confirmed cardiac dysfunction. Collagen content and organization was assessed through picrosirius red staining and fractal dimension (FD) analysis, respectively. Transcript abundance was estimated through reverse transcription-quantitative PCR (RT-qPCR). Cardiac dysfunction was confirmed by the reduction in maximum pulmonary artery velocity and pulmonary artery acceleration time. Through histomorphometric assessment, we found no differences in the interstitial collagen FD between groups. Regarding gene expression, myh7 gene expression was upregulated in the TPAH group. However, this did not occur with the S group. PAH also increased the mRNA abundance of col1a1 in the SPAH and TPAH groups. Moreover, the TPAH group showed a higher abundance of this gene when compared to the S group. With these findings, we concluded that preventive exercise had a positive impact on compensated hypertrophy during pulmonary hypertension. This can be explained in part by the modulation of the extracellular matrix and myosin gene expression in trained rats.

molecular biology↗