The nucleotide at position 1858 of hepatitis B virus has importance in chronic hepatitis B (HB) because a cytosine at nt 1858 effectively prevents virus escape through the precore TAG stop codon mutation. The relatedness between nt 1858 and genotypes was analyzed using a new genotyping method based on restriction fragment length polymorphism (RFLP) analysis of an S gene amplicon. Seventy-three gene bank sequences were analyzed by phylogenetic tree construction and RFLP prediction. A tree supporting the existence of 6 genotypes (A-F) was obtained, with C-1858 found in 9 of 9 A genotypes, 0 of 7 B, 0 of 19 C, 1 of 10 D, 0 of 2 E, and 3 of 3 F. Serum samples from 187 HB e antigen-positive chronic carriers were analyzed: Genotypes in northern Europeans were 60% A, 31% D; in southern Europeans and Middle Easterners 96% D; in Africans 53% A, 27% D, 20% E; and in East Asians 14% A, 43% B, 43% C. Cytosine at nt 1858 was found in 36 of 44 A, 0 of 32 B, 8 of 34 C, 0 of 59 D, 0 of 3 E, and 1 of 1 F genotype samples.
The changing spectrum of herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) infections makes it important to define the seroepidemiology of HSV. The object of this study was to determine the prevalence of HSV-1 and HSV-2 immunoglobulin G antibodies in a young Swedish population by investigating 2106 serum samples from people aged 0-19 y. Sera were tested in HSV type-specific enzyme-linked immunosorbent assays using glycoprotein G-1 (gG-1) and glycoprotein G-2 (gG-2) as antigens. The overall seroprevalence was 31% (95% CI 29-33) for HSV-1 and 0.5% (95% CI 0.2-0.9) for HSV-2. The HSV-1 seroprevalence was higher with increasing age, and significantly higher in the age cohort 15-19 y compared with 1-4-y-olds (37% vs 24%). The HSV-1 infection seemed to be acquired early in life. In the age cohort 1-2 y, the prevalence was over 20%, presumably reflecting an established viral infection. In adolescence the HSV-1 seroprevalence may reflect both oral and sexual transmission. The seroprevalence in the oldest age cohort did not differ significantly from that seen in a Swedish study in which sera were sampled from young girls in the 1970s.
Background The immunogenicity and safety following standard two-dose SARS-CoV-2 vaccination in patients with immune-mediated inflammatory diseases (IMIDs) are not well characterised, and data on third dose vaccination in this patient group are currently lacking. Methods This prospective, observational cohort study included adult patients on immunosuppressive therapy for Crohn’s disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriatic arthritis (PsA), and healthy controls receiving standard two-dose SARS CoV-2 vaccination. Patients with a weak serologic response (<100 AU/ml) were allotted a third vaccine dose. Serum samples were collected prior to, and after vaccination for analyses of antibodies to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. The aim of the study was to evaluate the immunogenicity and safety following standard and three dose SARS-CoV-2 vaccination in IMID patients on immunosuppressive therapies. Results A total of 1641 patients (280 CD, 195 UC, 566 RA, 305 SpA, 295 PsA, median age 52 [IQR 40–63], 899 [55%] women), and 1114 healthy controls (median age 43 [IQR 32–55], 854 [77%] women), were included in the study. After standard SARS-CoV-2 two dose vaccination, 1504 (91%) patients compared to 1096 (98%) healthy controls (p<0,001) were responders. Anti-RBD levels were lower in patients (median 619 AU/ml [IQR 192–4191]) than controls (median 3355 AU/ml [IQR 896–7849]), p<0,001. Response was shown in ≥90% of patients receiving methotrexate, tumor necrosis factor inhibitor (TNFi) monotherapy, ustekinumab, tozilizumab and vedolizumab, in 80–90% of patients receiving TNFi combination therapy and secukinumab and in ≤ 80% for JAK inhibitors (78%), and abatacept (53%) (Fig 1). Lower age (OR 0.96 [95% CI 0.95–0.98]) and receiving the mRNA-1273 vaccine (OR 5.4 [95% CI 2.4–11.9]) were predictors of response. Of 153 patients with a weak response receiving a third vaccine dose, 129 (84%) became responders. After standard two dose vaccination, adverse events (AE) were reported in 50% of patients and in 78% of controls, with a comparable safety profile. Following the third dose, 44% of patients reported AEs, without new safety issues emerging. No serious AEs were reported. Conclusion Response rate as well as anti-RBD levels were lower in IMID patients than healthy controls following standard vaccination. Third dose vaccination in serologically weak responders was safe and resulted in a response in most patients. Our data facilitate identification of patient groups at risk of an attenuated vaccine response eligible for post-vaccination serological monitoring. The data also support a third vaccine dose following standard SARS-CoV-2 vaccination to weak-responding IMID-patients.
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