Dataset Information

A cVLP-Based Vaccine Displaying Full-Length PCSK9 Elicits a Higher Reduction in Plasma PCSK9 Than Similar Peptide-Based cVLP Vaccines.

ABSTRACT: Administration of PCSK9-specific monoclonal antibodies, as well as peptide-based PCSK9 vaccines, can lower plasma LDL cholesterol by blocking PCSK9. However, these treatments also cause an increase in plasma PCSK9 levels, presumably due to the formation of immune complexes. Here, we utilize a versatile capsid virus-like particle (cVLP)-based vaccine platform to deliver both full-length (FL) PCSK9 and PCSK9-derived peptide antigens, to investigate whether induction of a broader polyclonal anti-PCSK9 antibody response would mediate more efficient clearance of plasma PCSK9. This head-to-head immunization study reveals a significantly increased capacity of the FL PCSK9 cVLP vaccine to opsonize and clear plasma PCSK9. These findings may have implications for the design of PCSK9 and other vaccines that should effectively mediate opsonization and immune clearance of target antigens.

SUBMITTER: Goksoyr L

PROVIDER: S-EPMC9864010 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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A cVLP-Based Vaccine Displaying Full-Length PCSK9 Elicits a Higher Reduction in Plasma PCSK9 Than Similar Peptide-Based cVLP Vaccines.

Goksøyr Louise L Skrzypczak Magdalena M Sampson Maureen M Nielsen Morten A MA Salanti Ali A Theander Thor G TG Remaley Alan T AT De Jongh Willem A WA Sander Adam F AF

Vaccines 20221220 1

Administration of PCSK9-specific monoclonal antibodies, as well as peptide-based PCSK9 vaccines, can lower plasma LDL cholesterol by blocking PCSK9. However, these treatments also cause an increase in plasma PCSK9 levels, presumably due to the formation of immune complexes. Here, we utilize a versatile capsid virus-like particle (cVLP)-based vaccine platform to deliver both full-length (FL) PCSK9 and PCSK9-derived peptide antigens, to investigate whether induction of a broader polyclonal anti-PC ...[more]

PMID: 36679847

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Project description:PurposeTo assess whether continuous embryo culture involves better embryological and/or clinical outcomes than sequential.MethodsProspective study at a private IVF center. All consecutive IVF cycles (September 2013-2015) fulfilling the inclusion criteria underwent embryo culture in either Continuous-Single-Culture-Media (CSCM, n = 972) or sequential media (Quinn's Advantage, n = 514), respectively. ICSI, blastocyst culture in either standard (MINC) or undisturbed (Embryoscope) incubation, transfer (until September 2016), and pregnancy follow-up (until September 2017) were performed. When aneuploidy testing was required, trophectoderm biopsy and qPCR were performed. Sub-analyses and logistic regression corrected for confounders were performed. The primary outcomes were overall blastocyst rate per oocyte and mean blastocyst rate per cycle. The sample size was defined to reach 95 and 80% statistical power for the former and the latter outcome, respectively. Secondary outcomes were euploidy (if assessed), cumulative delivery rates, gestational age, and birthweight.ResultsContinuous embryo culture resulted into a higher overall blastocyst rate per inseminated oocyte than sequential (n = 2211/5841, 37.9% vs. 1073/3216, 33.4%; p < 0.01), confirmed also from a cycle-based analysis (mean blastocyst rate: 38.7% ± 29.7% vs. 34.3% ± 29.4%; p = 0.01). The continuous media (OR = 1.23), the undisturbed incubation system (OR = 1.22), the maternal age (OR = 0.92), and the sperm factor (OR = 0.85) were outlined as positive predictors of blastulation. However, the cumulative delivery rates per ended cycle (i.e., delivery achieved or no blastocyst produced or left; > 90%) were comparable in the two groups (n = 244/903, 27.0% vs. 129/475, 27.2%). The neonatal outcomes were similar.ConclusionsContinuous culture involves better embryological but similar clinical outcomes than sequential. This large prospective study supports the absence of clinical disparity among the two approaches.

Dataset Information

A cVLP-Based Vaccine Displaying Full-Length PCSK9 Elicits a Higher Reduction in Plasma PCSK9 Than Similar Peptide-Based cVLP Vaccines.

Publications

A cVLP-Based Vaccine Displaying Full-Length PCSK9 Elicits a Higher Reduction in Plasma PCSK9 Than Similar Peptide-Based cVLP Vaccines.

Similar Datasets

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