Your browser doesn't support javascript.
loading
Cholesterol reduction by immunization with a PCSK9 mimic.
Zhang, Baoshan; Chuang, Gwo-Yu; Biju, Andrea; Biner, Daniel; Cheng, Jiaxuan; Wang, Yiran; Bao, Saran; Chao, Cara W; Lei, Haotian; Liu, Tracy; Nazzari, Alexandra F; Yang, Yongping; Zhou, Tongqing; Chen, Steven J; Chen, Xuejun; Kong, Wing-Pui; Ou, Li; Parchment, Danealle K; Sarfo, Edward K; SiMa, HaoMin; Todd, John-Paul; Wang, Shuishu; Woodward, Ruth A; Cheng, Cheng; Rawi, Reda; Mascola, John R; Kwong, Peter D.
Afiliação
  • Zhang B; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Chuang GY; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Biju A; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Biner D; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Cheng J; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Wang Y; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Bao S; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Chao CW; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Lei H; Research Technologies Branch, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Liu T; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Nazzari AF; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Yang Y; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Zhou T; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Chen SJ; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Chen X; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Kong WP; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Ou L; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Parchment DK; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Sarfo EK; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • SiMa H; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Todd JP; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Wang S; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Woodward RA; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Cheng C; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Rawi R; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Mascola JR; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
  • Kwong PD; Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA. Electronic address: pdkwong@nih.gov.
Cell Rep ; 43(6): 114285, 2024 Jun 25.
Article em En | MEDLINE | ID: mdl-38819987
ABSTRACT
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a plasma protein that controls cholesterol homeostasis. Here, we design a human PCSK9 mimic, named HIT01, with no consecutive 9-residue stretch in common with any human protein as a potential heart attack vaccine. Murine immunizations with HIT01 reduce low-density lipoprotein (LDL) and cholesterol levels by 40% and 30%, respectively. Immunization of cynomolgus macaques with HIT01-K21Q-R218E, a cleavage-resistant variant, elicits high-titer PCSK9-directed antibody responses and significantly reduces serum levels of cholesterol 2 weeks after each immunization. However, HIT01-K21Q-R218E immunizations also increase serum PCSK9 levels by up to 5-fold, likely due to PCSK9-binding antibodies altering the half-life of PCSK9. While vaccination with a PCSK9 mimic can induce antibodies that block interactions of PCSK9 with the LDL receptor, PCSK9-binding antibodies appear to alter homeostatic levels of PCSK9, thereby confounding its vaccine impact. Our results nevertheless suggest a mechanism for increasing the half-life of soluble regulatory factors by vaccination.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Colesterol / Imunização / Pró-Proteína Convertase 9 / Macaca fascicularis Idioma: En Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Colesterol / Imunização / Pró-Proteína Convertase 9 / Macaca fascicularis Idioma: En Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos