Reducing CVD Risk Using a Vaccine-Based Approach

T-cell receptors interact with MHC class II antigen complexes
T-cell receptors interact with MHC class II antigen complexes
In preclinical animal studies, vaccination against PSCK9 lowered serum lipids and vaccination against ApoC3 lowered serum triglyceride levels.

Vaccination against proprotein convertase subtilisin/kexin type 9 (PSCK9) and apolipoprotein C-III (ApoC3) lowers serum triglyceride levels and may serve as a means of reducing the risk of developing cardiovascular disease (CVD), according to research presented at the 66th Annual Scientific Session & Expo of the American College of Cardiology.

Because loss-of-function PCSK9 and ApoC3 mutations have been associated with low serum lipids and reduced rates of CVD without any evident medical complications, Ingrid E. Lindquist, from the University of New Mexico School of Medicine in Albuquerque, and colleagues, generated vaccines targeting PCSK9 and ApoC3 host proteins using a flexible virus-like particle-based vaccine platform technology.

“Display of antigens at high valency on the surface of virus-like particles is an effective technique for enhancing the immunogenicity of antigens, even self-antigens such as PSCK9 and ApoC3,” the researchers noted.

In preclinical studies, mice and non-human primates were immunized with virus-like particles and antibodies against PCSK9 or ApoC3. “Peptides derived from PCSK9 or ApoC3 were displayed on bacteriophage virus-like particles.”

Plasma lipid levels were measured in both mice and macaques, and researchers assessed the effectiveness of the vaccination along with statin therapy.

High titer antibody responses were effectively induced in both mice and macaques.  A reduction in total serum cholesterol (28%) and triglycerides (51%) was observed in mice immunized against PCSK9.  Furthermore, a 30% to 40% reduction in triglyceride levels relative to pre-vaccination levels was observed in mice immunized against ApoC3.

In macaques immunized against PCSK9 in addition to receiving a statin, low-density lipoprotein cholesterol (LDL-C) decreased 30% to 40% vs 5% in macaques that received only a statin.

“These data demonstrate that host-immunity to PCSK9 or ApoC3 and concomitant reduction in serum lipid levels can be achieved using virus-like particle-based vaccines,” the researchers concluded.

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Lindquist IE, Crossey E, Amar M, Remaley A, Chackerian B. A vaccine-based strategy for reducing cardiovascular disease risk factors. Abstract 1187-054. Presented at: the 66th Scientific Session & Expo of the American College of Cardiology. March 17-19, 2017; Washington, DC.