A vaccine candidate could improve obesity-related disorders

Dyslipidemia is a major risk factor for cardiovascular disease, which can dramatically shorten life expectancy. Recently, Professor Yuichi Oike and his team of scientists from Kumamoto University, Japan, successfully developed a peptide vaccine that can relieve dyslipidemia disorders and proven effective in mice. The new vaccine could become one of the most cost-effective treatments for obesity / cholesterol-related disorders like atherosclerosis and fatty liver disease.

Cardiovascular disease (CVD) is involved in almost 32% of all deaths worldwide. Increased levels of low density lipoprotein-cholesterol (LDL-C) and triglycerides (TG) characterize dyslipidemia, a major risk factor for CVD. These can speed up the progression of fatty liver disease, which can lead to long-term liver cancer. With the increase in the worldwide frequency of fatty liver disease, the market is soon expected to be flooded with expensive drugs known as “biopharmaceuticals” which are currently in clinical trials. These drugs, however, will require long-term treatment which can be a big barrier to global health care coverage. Therefore, scientists are currently focusing their efforts on the development of new therapeutic agents that are both effective and cost-effective.

In their new study, published in the Cellular Reports Medicine, Professor Yuichi Oike and his team developed a new peptide vaccine to fight dyslipidemia associated with obesity and studied its effects on obese mouse models. The article was published in Volume 2, Issue 11 of the journal on November 16, 2021.

To develop the vaccine, they chose to target the angiopoietin-like protein 3 (ANGPTL3), which has recently gained attention in strategies to reduce LDL-C and TG levels in the blood. The results of the ANGPTL3 peptide vaccine were validated in their trials in mice, which confirmed its efficacy for approximately 6 months without any reported toxicity, providing evidence that the new treatment is safe and without side effects.

Peptide vaccines are well known to be cheaper to manufacture than biopharmaceuticals, making them preferable in terms of medical economics. To meet this need, the team has developed vaccines targeting three peptides (or short chains of amino acids) of ANGPTL3, namely epitope 1 (E1), E2 and E3. The peptide vaccines were then injected into a mouse model of obesity-induced dyslipidemia. The researchers were delighted to see that the E3 peptide vaccine effectively reduced dyslipidemia in mice and produced antibodies that lasted 6 months. “Peptide vaccine selectively induces antibody-mediated immunity to produce neutralizing antibodies suppressing ANGPTL3 functionSays Professor Oike.

Because LDL-C is easily deposited in the walls of blood vessels and obstructs blood flow, it is commonly referred to as “bad cholesterol”. This obstruction can cause atherosclerosis and lead to heart failure. To see if their vaccine worked against the disease, the researchers gave E3 to model mice with severe familial hypercholesterolemia on a high-cholesterol diet and found that it improved dyslipidemia and atherosclerosis.

When asked how this vaccine works and whether similar benefits will also be seen in humans, Professor Oike says: “E3 vaccination in mice decreases circulating levels of LDL-C and TG in the blood. Because the mouse E3 sequence is identical to the corresponding human sequence, E3 could potentially be studied in clinical studies”.

Professor Oike and colleagues believe this vaccination will help patients in economically disadvantaged areas who require long-term treatment for dyslipidemia or related conditions. “Expensive antibody treatments for dyslipidemia require monthly injections, while our vaccination is effective for up to 6 months“, he explains. “Vaccine Expected to Become One of New Economical Therapeutic Choices for Dyslipidemia and Dyslipidemia-Related Disorders“, he adds.

The authors plan to conduct preclinical research to test the vaccine’s efficacy and safety, as well as to make improvements to prolong its efficacy. Professor Oike continues: “We will change the vaccine formulation and optimize dosage and administration for clinical trials. Re-vaccination every 5 or 6 months could maintain the therapeutic efficacy of E3 vaccine therapy, and further investigation is needed to see if a booster vaccination would prolong its durability. “

Reference: Fukami H, Morinaga J, Nakagami H, et al. The vaccine targeting ANGPTL3 improves dyslipidemia and associated diseases in mouse models of obese dyslipidemia and familial hypercholesterolemia. CR Med. 2021; 2 (11). do I: 10.1016 / j.xcrm.2021.100446

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