We report on prime-boost vaccine regimens with two simian adenovirus (Ad) vectors (SAdV) or two human serotype Ad vectors (HAdV) expressing Gag and gp160 of simian immunodeficiency virus (SIV)mac239tested in HAdV-seropositive rhesus macaques (RMs) repeatedly challenged rectally with low doses of SIVmac251.Both vaccine regimens reduced set point and peak viral loads (PVL) and accelerated viral clearance. In SAdV-vaccinated controller genotype RMs resistance against infection correlated with levels of envelope (Env)-specific antibody (Ab) titers. In both vaccine groups CD8+T cells controlled viral loads (VL) upon infection. Circulating CD4+and CD8+T cells showed significant changes in their transcriptome over time following vaccination, which differed between the vaccine groups. T cells from SIV-resistant RMs had unique transcriptional profiles indicating that both follicular T helper (TFH) cell responses and highly activated CD8+T cells may play a role in protection.
by
Brian T. Costello;
Eric R. Silverman;
Rami Doukky;
Lynne T. Braun;
Neelum T. Aggarwal;
Youping Deng;
Yan Li;
Gina Lundberg;
Kim A. Williams;
Anabelle S. Volgman
Background: Approximately 20% of the population has elevated circulating levels of lipoprotein(a) (Lp[a]), one of the most robust predictors of cardiovascular disease risk. This is particularly true for women.
Hypothesis: Many female patients with "normal" traditional risk factors or low atherosclerotic cardiovascular disease (ASCVD) risk scores may harbor high risk related to elevated levels of Lp(a).
Methods: A retrospective, cross-sectional study of consecutive female patients presenting to Heart Centers for Women was performed. Discordance between low-density lipoprotein cholesterol (LDL-C) and Lp(a) was determined. The ASCVD risk and Reynolds Risk Score models A (RRS-A) and B (RRS-B) were calculated, and level of agreement in patients meeting treatment threshold (≥7.5% for ASCVD, ≥10% for RRS-A and RRS-B) were compared.
Results: Among 713 women, 290 (41%) had elevated Lp(a); however, LDL-C and Lp(a) were weakly correlated (r = 0.08). Significant discordance was observed between abnormal LDL-C and Lp(a) levels (McNemar P = 0.03). There was moderate correlation between RRS-A and ASCVD risk (r = 0.71, P < 0.001), and Bland-Altman plot showed diminished correlation with increased risk. More patients met treatment threshold by ASCVD risk estimation, but nearly 1 out of 20 patients met treatment threshold by RRS-A but not ASCVD score.
Conclusions: There is high prevalence of elevated Lp(a) among women presenting to Heart Centers for Women. Although traditional risk markers such as elevated LDL-C or high ASCVD risk may be absent in some women, elevated Lp(a) may identify patients who may benefit from aggressive risk-factor modification and pharmacologic therapy.