• https://onlinelibrary.wiley.com/doi/full/10.1002/eji.201847584

    From Treon Verdery@21:1/5 to All on Wed Oct 12 09:23:50 2022
    Vaccination with MHC‐II‐restricted peptides from Apolipoprotein B (ApoB) with complete and incomplete Freund's adjuvant (CFA/IFA) is known to protect mice from atherosclerosis. This vaccination induces antigen‐specific IgG1 and IgG2c antibody
    responses and a robust CD4 T cell response in lymph nodes. However, CFA/IFA cannot be used in humans. To find a clinically applicable adjuvant, we tested the effect of vaccinating Apoe‐deficient mice with ApoB peptide P6 (TGAYSNASSTESASY). In a broad
    screening experiment, Addavax, a squalene‐based oil‐in‐water adjuvant similar to MF59, was the only adjuvant that showed similar efficacy as CFA/IFA. This was confirmed in a confirmation experiment for both the aortic arch and whole aorta analyzed
    by en face analysis after atherosclerotic lesion staining. Mechanistically, restimulated peritoneal cells from mice immunized with P6 in Addavax released significant amounts of IL‐10. Unlike P6 in CFA/IFA, vaccination with P6 in Addavax did not induce
    any detectable IgG1 or IgG2c antibodies to P6. These data suggest that squalene‐based adjuvants such as MF59 are good candidate adjuvants for developing a clinically effective atherosclerosis vaccine.

    “Recently, a squalene‐based adjuvant and monophosphoryl lipid A were approved in pandemic influenza virus vaccines 19, 20 and human papilloma virus vaccines for cervical cancer 21.”

    “Addavax is a squalene‐based adjuvant similar to MF59, which is FDA‐approved and licensed in Europe for a seasonal influenza vaccine for elderly people 30. Here, we report that vaccinating Apoe‐deficient (Apoe−/−) mice with ApoB P6 in Addavax
    was as atheroprotective as P6 in CFA/IFA.”

    “We first assessed atherosclerotic lesion size by en‐face analysis of pinned and Sudan‐IV‐stained aortas (Supporting Information Fig. 1B and 1C). The lesion area was 18% of the total area in the aortic arches of mice immunized with P6 alone. As
    expected, lesion area was significantly reduced by ∼50% when mice were immunized with P6 in CFA/IFA. A similar reduction was observed in mice immunized with P6 in Addavax (Supporting Information Fig. 1B and 1C).”

    Note: addavax is avaialble online for about $264/10ml. https://www.invivogen.com/addavax The antiatherosclerotic peptide can be ordered, and the protocol with mice has a subcutaneous injection every 2 weeks for 5 weeks.

    It is possible that this “P6” is the same as the v6 antiatherosclerotic vaccine in phase (something) human clinical trials. “Atherosclerosis vaccine, V6” https://clinicaltrials.gov/ct2/show/NCT03042741 an oral antiatherosclerosis vaccine. The
    human dose and frequency resource complements the mouse data, and the oral formulation suggests the possibility that after an injected version, surplus peptide could be used to make a nasal spray version dosed at the same frequency as the oral version.
    study will evaluate daily dose of one V6 pill [human] administered for one month in placebo-controlled, randomized, double-blind phase 3 trial”

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