Variant Allele of ALDH2, rs671, Associates with Attenuated Post-Vaccination Response in Anti-SARS-CoV-2 Spike Protein IgG: A Prospective Study in the Japanese General Population

Uncovering the predictors of vaccine immunogenicity is essential for infection control. We have reported that the most prevalent polymorphism of the aldehyde dehydrogenase 2 gene (ALDH2), rs671, may be associated with an attenuated immune system. To test the inverse relationship between rs671 and antibody production after COVID-19 vaccination, the levels of anti-SARS-CoV-2 Spike protein S1 subunit (S1) IgG were repeatedly measured for four months before and after vaccination with BNT162b2 or mRNA-1273, in 88 Japanese workers and students (including 45 females, aged 21–56 years, with an rs671 variant allele frequency of 0.3). The mixed model including fixed effects of the vaccine type, weeks post vaccination (categorical variable), sex, age, height, smoking status, ethanol intake, exercise habit, perceived stress, steroid use, allergic diseases, and dyslipidemia, indicated an inverse association between log-transformed anti-S1 IgG levels and the number of rs671 variant alleles (partial regression coefficient = −0.15, p = 0.002). Our study indicated for the first time that the variant allele of ALDH2, rs671, is associated with the attenuated immunogenicity of COVID-19 mRNA vaccines. Our finding may provide a basis for personalized disease prevention based on a genetic polymorphism that is prevalent among East Asians

Preventive effects of pneumococcal and influenza vaccines on community-acquired pneumonia in older individuals in Japan: a case-control study

At present, there are few reports that have clarified the effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPSV23) against all-cause pneumonia or pneumococcal pneumonia in community-acquired pneumonia (CAP) in older individuals in Japan. We conducted a hospital-based matched case-control study to investigate separately the preventive effects of PPSV23 and trivalent influenza vaccine (TIV) on all-cause CAP and pneumococcal CAP in older individuals in Japan. Cases were individuals aged 65 years or older who were newly diagnosed with CAP from October 2010 to September 2014. Two control patients with a different disease (one respiratory medicine and one non-respiratory medicine) matched for sex, age, date of outpatient visit, and medical institution were selected for each case. Odds ratios (ORs) and 95% confidence intervals (CIs) of PPSV23 and TIV for the occurrence of all-cause CAP and pneumococcal CAP were calculated using conditional and unconditional logistic regression models. The analysis included 161 cases and 308 controls from the 4-year period. The adjusted OR for the occurrence of all-cause CAP was 0.76 (95%CI = 0.44–1.32) with PPSV23 vaccination and 0.79 (95%CI = 0.50–1.25) with TIV vaccination compared with unvaccinated individuals. When the outcome index was restricted to pneumococcal CAP, the adjusted OR significantly decreased to 0.23 (95%CI = 0.08–0.66) with PPSV23 vaccination, but not with TIV vaccination (adjusted OR = 0.65, 95%CI = 0.31–1.36). PPSV23 vaccination is likely effective in reducing incidence of pneumococcal CAP in older individuals, although its preventive effect for all-cause CAP has not been achieved

ssDNA is not superior to dsDNA as long HDR donors for CRISPR-mediated endogenous gene tagging in human diploid RPE1 and HCT116 cells

Abstract Background Recent advances in CRISPR technology have enabled us to perform gene knock-in in various species and cell lines. CRISPR-mediated knock-in requires donor DNA which serves as a template for homology-directed repair (HDR). For knock-in of short sequences or base substitutions, ssDNA donors are frequently used among various other forms of HDR donors, such as linear dsDNA. However, partly due to the complexity of long ssDNA preparation, it remains unclear whether ssDNA is the optimal type of HDR donors for insertion of long transgenes such as fluorescent reporters in human cells. Results In this study, we established a nuclease-based simple method for the preparation of long ssDNA with high yield and purity, and comprehensively compared the performance of ssDNA and dsDNA donors with 90 bases of homology arms for endogenous gene tagging with long transgenes in human diploid RPE1 and HCT116 cells. Quantification using flow cytometry revealed lower efficiency of endogenous fluorescent tagging with ssDNA donors than with dsDNA. By analyzing knock-in outcomes using long-read amplicon sequencing and a classification framework, a variety of mis-integration events were detected regardless of the donor type. Importantly, the ratio of precise insertion was lower with ssDNA donors than with dsDNA. Moreover, in off-target integration analyses using donors without homology arms, ssDNA and dsDNA were comparably prone to non-homologous integration. Conclusions These results indicate that ssDNA is not superior to dsDNA as long HDR donors with relatively short homology arms for gene knock-in in human RPE1 and HCT116 cells