A personalized antibody score for predicting individual COVID-19 vaccine-elicited antibody levels from basic demographic and health information

Antibody titers wane after two-dose COVID-19 vaccinations, but individual variation in vaccine-elicited antibody dynamics remains to be explored. Here, we created a personalized antibody score that enables individuals to infer their antibody status by use of a simple calculation. We recently developed a mathematical model of B cell differentiation to accurately interpolate the longitudinal data from a community-based cohort in Fukushima, Japan, which consists of 2,159 individuals who underwent serum sampling two or three times after a two-dose vaccination with either BNT162b2 or mRNA-1273. Using the individually reconstructed time course of the vaccine-elicited antibody response, we first elucidated individual background factors that contributed to the main features of antibody dynamics, i.e., the peak, the duration, and the area under the curve. We found that increasing age was a negative factor and a longer interval between the two doses was a positive factor for individual antibody level. We also found that the presence of underlying disease and the use of medication affected antibody levels negatively, whereas the presence of adverse reactions upon vaccination affected antibody levels positively. We then applied to these factors a recently proposed computational method to optimally fit clinical scores, which resulted in an integer-based score that can be used to evaluate the antibody status of individuals from their basic demographic and health information. This score can be easily calculated by individuals themselves or by medical practitioners. There is a potential usefulness of this score for identifying vulnerable populations and encouraging them to get booster vaccinations. Significance statementDifferent individuals show different antibody titers even after the same COVID-19 vaccinations, making some individuals more prone to breakthrough infections than others. Such variability remains to be clarified. Here we used mathematical modeling to reconstruct individual post-vaccination antibody dynamics from a cohort of 2,159 individuals in Fukushima, Japan. Machine learning identified several positive and negative factors affecting individual antibody titers. Positive factors included adverse reactions after vaccinations and a longer interval between two vaccinations. Negative factors included age, underlying medical conditions, and medications. We combined these factors and developed an "antibody score" to estimate individual antibody dynamics from basic demographic and health information. This score can help to guide individual decision-making about taking further precautions against COVID-19.

Stratifying elicited antibody dynamics after two doses of SARS-CoV-2 vaccine in a community-based cohort in Fukushima, Japan

Recent studies have provided insights into the effect of vaccine boosters on recall immunity. Given the limited global supply of COVID-19 vaccines, identifying vulnerable populations with lower sustained vaccine-elicited antibody titers is important for targeting individuals for booster vaccinations. Here we investigated longitudinal data in a cohort of 2,526 people in Fukushima, Japan, from April 2021 to December 2021. Antibody titers following two doses of a COVID-19 vaccine were repeatedly monitored and information on lifestyle habits, comorbidities, adverse reactions, and medication use was collected. Using mathematical modeling and machine learning, we stratified the time-course patterns of antibody titers and identified vulnerable populations with low sustained antibody titers. Moreover, we showed that only 5.7% of the participants in our cohort were part of the "durable" population with high sustained antibody titers, which suggests that this durable population might be overlooked in small cohorts. We also found large variation in antibody waning within our cohort. There is a potential usefulness of our approach for identifying the neglected vulnerable population.

The serological diversity of serum IgG/IgA/IgM against the SARS-CoV-2 nucleoprotein, spike, and receptor-binding domain and neutralizing antibodies in patients with COVID-19 in Japan

ObjectivesTo compare the temporal changes of IgM, IgG, and IgA antibodies against the SARS-CoV-2 nucleoprotein, S1 subunit, and receptor binding domain and neutralizing antibodies (NAbs) against SARS-CoV-2 in patients with COVID-19. MethodsA total of five patients in Nissan Tamagawa Hospital, Tokyo, Japan confirmed COVID-19 from August 8, 2020 to August 14, 2020 were investigated. Serum samples were acquired multiple times from 0 to 76 days after symptom onset. Using a fully automated CLIA analyzer, we measured the levels of IgG, IgA, and IgM against the SARS-CoV-2 N, S1, and RBD and NAbs against SARS-CoV-2. ResultsThe levels of IgG antibodies against SARS-CoV-2 structural proteins increased over time in all cases but IgM and IgA levels against SARS-CoV-2 showed different increasing trends among individuals in the early stage. In particular, we observed IgA antibodies increasing before IgG and IgM in 3/5 cases. The NAb levels against SARS-CoV-2 increased and kept above 10 AU/mL more than around 70 days after symptom onset in all cases. Furthermore, in the early stage, NAb levels were more than cut off value in 4/5 COVID-19 patients some of whose antibodies against RBD didnt exceed 10 AU/mL. ConclusionsOur findings indicate that patients with COVID-19 should be examined for IgG, IgA and IgM antibodies against SARS-CoV-2 structural proteins and NAbs against SARS-CoV-2 in addition to conventional antibody testing methods for SARS-CoV-2 (IgG and IgM kits) to analyze the diversity of patients immune mechanisms.

In vitro model of atherosclerosis using coculture of arterial wall cells and macrophage

In order to determine the precise mechanism of the interactions between different types of cells, which are common phenomena in tissues and organs, the importance of coculture techniques are becoming increasingly important. In the area of cardiology, artificial arteries have been developed, based on the understanding of physiological communication of the arterial smooth muscle cells (SMC), endothelial cells (EC), and the extracellular matrix (ECM). In the study of atherosclerosis, the modification of low-density lipoprotein (LDL), which result in the recruitment and accumulation of white blood cells, especially, monocytes/macrophages, and foam cell formation, are hypothesized. Although there are well known animal models, an in vitro model of atherogenesis with a precisely known atherogenesis mechanism has not yet been developed. In this paper, an arterial wall reconstruction model using rabbit primary cultivated aortic SMCs and ECs, was shown. In addition, human peripheral monocytes were used and the transmigration of monocytes was observed by scanning electron and laser confocal microscopy. Monocyte differentiation into macrophages was shown by immunohistochemistry and comprehensive gene expression analysis. With the modified form of LDL, the macrophages were observed to accumulate lipids with a foamy appearance and differentiate into the foam cells in the ECM between the ECs and SMCs in the area of our coculture model.

A Case of Thromboexclusion with Axillo-Bifemoral Bypass Grafting for Unresectable Abdominal Aortic Aneurysm / 日本心臓血管外科学会雑誌

We performed the thromboexclusion procedure with reconstruction by an axillo-bifemoral bypass for unresectable abdominal aortic aneurysm combined with chronic renal faliure, and obtained satisfactory postoperative result. The patient was a 68-year-old male who suffered from a huge abdominal aortic aneurysm (AAA) and had a history of hypertension and chronic renal failure. The AAA was accompanied with a saccular portion 10cm in diameter which compressed and eroded the vertebral body. Aortic cross-clamping above the bilateral renal arteries was inevitable for resection in spite of the renal dysfunction. We decided that direct manipulation of the aneurysm was impossible despite it being on the verge of rupture, considering the high operative mortality. We employed the exclusion-bypass method to stabilize the aneurysm, that is, we constructed axillo-bifemoral bypass using a knitted Dacron T-graft 8mm in diameter and then intercepted the bilateral common iliac arteries by suture closure. Postoperative intraaneurysmal thrombosis progressed rapidly from the distal side, then it halted just below the bilateral renal arteries on the 12th postoperative day. Renal arterial flow was maintained and renal function improved. Bleeding from the operative wound occurred suddenly on the 5th postoperative day. Although this appeared to be disseminated intravascular coagulation initially, it had resulted from augmentation of fibrinolysis due do acceleration of coagulation. The markers of fibrinolysis for example α₂ plasmin inhibitor (α₂PI) and plasmin-α₂ plasmin inhibitor complex (PIC) were useful for diagnosis, and tranexam acid and aprotinin were effective for therapy. Although the exclusion-bypass method is technically less invasive and useful for high-risk AAA, the postoperative management is not easy because of the acceleration of the coagulation-fibrinolysis system.