Journal: Vaccines

Article Title: Pre-Clinical Evaluation of the Nanoliposomal antiPCSK9 Vaccine in Healthy Non-Human Primates

doi: 10.3390/vaccines9070749

Figure Lengend Snippet: Sequence of the immunogenic peptides used in the present study.

Article Snippet: To determine the immunogenicity of the L-IFPTA vaccine, titers of antiPCSK9-specific IgG were measured by ELISA technique, using PCSK9 peptide (ChinaPeptides Co., Ltd., Shanghai, China) as the antigen [ ].

Techniques: Sequencing, Immunopeptidomics

Journal: Vaccines

Article Title: Pre-Clinical Evaluation of the Nanoliposomal antiPCSK9 Vaccine in Healthy Non-Human Primates

doi: 10.3390/vaccines9070749

Figure Lengend Snippet: ( A ) Antibody titer (ODmax/2) against PCSK9 in vaccinated monkeys at pre-vaccination (W0) and post-vaccination (W8) time-points. ( B ) The exponential increase in antiPCSK9 antibody titer (ODmax/2) over 8 weeks post prime vaccination, generated upon 4 vaccinations in a biweekly interval (signed by arrows). Values are means ± SD ( n = 5).

Article Snippet: To determine the immunogenicity of the L-IFPTA vaccine, titers of antiPCSK9-specific IgG were measured by ELISA technique, using PCSK9 peptide (ChinaPeptides Co., Ltd., Shanghai, China) as the antigen [ ].

Techniques: Generated

Journal: Vaccines

Article Title: Pre-Clinical Evaluation of the Nanoliposomal antiPCSK9 Vaccine in Healthy Non-Human Primates

doi: 10.3390/vaccines9070749

Figure Lengend Snippet: In vitro PCSK9/LDLR binding assay. Vaccine-produced antiPCSK9 antibodies suppress the interaction of PCSK9 and LDLR. A plasma sample of monkeys at post-vaccination time-point (W8) could reduce PCSK9 binding to LDLR by −33 ± 7%, when compared with a plasma sample of pre-vaccination ones (W0). Values are means ± SD; n = 3 replicates of the pooled samples of 5 monkeys. The significance compared to pre-vaccination values was analyzed by an unpaired two-tailed Student’s t -test. Statistical differences at p -values less than 0.05 were considered to be significant.

Article Snippet: To determine the immunogenicity of the L-IFPTA vaccine, titers of antiPCSK9-specific IgG were measured by ELISA technique, using PCSK9 peptide (ChinaPeptides Co., Ltd., Shanghai, China) as the antigen [ ].

Techniques: In Vitro, Binding Assay, Produced, Clinical Proteomics, Two Tailed Test

Journal: PLoS ONE

Article Title: Development of vaccine for dyslipidemia targeted to a proprotein convertase subtilisin/kexin type 9 (PCSK9) epitope in mice

doi: 10.1371/journal.pone.0191895

Figure Lengend Snippet: Two candidate vaccines (V1 and V2 vaccines) or control (KLH) was injected (5 μg peptide per mouse) (N = 4 per group). (A) The antibody titers against candidate PCSK9 peptides conjugated with bovine serum albumin were evaluated pre-immunization (pre) and post-immunization (4 or 8 weeks), and the results are expressed as half-maximal binding (optical density: OD50%). Significance values were obtained with a 2-factor repeated-measure ANOVA with subsequent Tukey’s multiple comparisons tests. (B) Mouse plasma PCSK9 levels were measured at pre-immunization (pre) and post-immunization (4 weeks) time points. Significance values were obtained using two-way ANOVA with subsequent Tukey’s multiple comparisons test. (C and D) Mean values of TC and TG levels (mg/dL) were measured post-immunization (4 weeks). Significance values relative to KLH (*P<0.05) were obtained with one-way ANOVA with subsequent Tukey’s multiple comparisons tests. All data in this Figure are expressed as the means ± SEM. *P<0.05, **P<0.01, and ****P<0.0001.

Article Snippet: Candidate PCSK9 peptides were conjugated with bovine serum albumin at its N-terminus via suberic acid bis (PEPTIDE INSTITUTE Inc., Osaka, Japan).

Techniques: Injection, Binding Assay

Journal: PLoS ONE

Article Title: Development of vaccine for dyslipidemia targeted to a proprotein convertase subtilisin/kexin type 9 (PCSK9) epitope in mice

doi: 10.1371/journal.pone.0191895

Figure Lengend Snippet: PCSK9 vaccine (V2 vaccine) or control (Saline) was injected at different doses (Low; 5 μg and High; 50 μg peptides per mouse) three times in biweekly intervals (0, 2, and 4 weeks). (A) Anti-PCSK9 antibody titers (OD50%) were evaluated at pre-immunization (pre) and post-immunization time points (2, 4, 6, 8, 12, 16, 20, and 24 weeks). Data are presented as the average of each groups; error bars indicate the SEM. **P<0.01 and ****P<0.0001 show significant changes between low dose group and saline group. ††††P<0.0001 shows significant changes between high dose group and saline group. (B) PCSK9 levels in plasma samples from pre-immunized (pre) and post-immunized (6 weeks) mice. Bars represent mean levels of detected mouse PCSK9 levels in plasma samples, and error bars represent ± SEM. Significance values relative to saline group (*P<0.05, ***P<0.001) were obtained using two-way ANOVA with subsequent Tukey's multiple comparisons tests. (C) Cell-surface LDLR levels in liver hepatocytes were measured in immunized mice at 6 weeks post-immunization via ELISA. The results are presented as a fold-increase relative to saline-treated groups. Significance values relative to saline (****P<0.0001) were obtained with one-way ANOVA with subsequent Tukey’s tests for multiple comparisons. All data in this Figure are expressed as the means ± SEM.

Article Snippet: Candidate PCSK9 peptides were conjugated with bovine serum albumin at its N-terminus via suberic acid bis (PEPTIDE INSTITUTE Inc., Osaka, Japan).

Techniques: Injection, Enzyme-linked Immunosorbent Assay

Journal: PLoS ONE

Article Title: Development of vaccine for dyslipidemia targeted to a proprotein convertase subtilisin/kexin type 9 (PCSK9) epitope in mice

doi: 10.1371/journal.pone.0191895

Figure Lengend Snippet: PCSK9 vaccine (V2 vaccine) was injected at a low dose (5 μg) or high dose (50 μg) peptide per mouse three times in biweekly intervals (0, 2, and 4 weeks), and mice were followed up until 24 weeks. Plasma TC levels (A), detailed cholesterol lipoprotein profile (B), and plasma TG levels (C) were measured at the particular time points (pre-immunization, 6 and 24 weeks after first immunization). Significance values were obtained with a 2-factor repeated-measure ANOVA with subsequent Tukey’s multiple comparisons tests. All data in this Figure are expressed as the means ± SEM. **P<0.01 ***P<0.001, and ****P<0.0001.

Article Snippet: Candidate PCSK9 peptides were conjugated with bovine serum albumin at its N-terminus via suberic acid bis (PEPTIDE INSTITUTE Inc., Osaka, Japan).

Techniques: Injection

Journal: PLoS ONE

Article Title: Development of vaccine for dyslipidemia targeted to a proprotein convertase subtilisin/kexin type 9 (PCSK9) epitope in mice

doi: 10.1371/journal.pone.0191895

Figure Lengend Snippet: Splenocytes (10 6 cells per well) from V2 vaccine-immunized mice were stimulated with a candidate PCSK9 peptide (V2 peptide), recombinant mouse PCSK9, KLH, or PHA at 10 μg/mL. (A) Representative images of black spots are shown detecting INF-γ and IL-4 in splenocytes. (B) Cytokine (IFN-γ and IL-4)–producing cells were quantified. All data are expressed as the means ± SEM. Significance values were obtained using two-way ANOVA with subsequent Tukey’s multiple comparisons tests.

Article Snippet: Candidate PCSK9 peptides were conjugated with bovine serum albumin at its N-terminus via suberic acid bis (PEPTIDE INSTITUTE Inc., Osaka, Japan).

Techniques: Recombinant