Background & Aims The development of COVID-19 vaccines has progressed with encouraging safety and efficacy data. Concerns have been raised about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in NAFLD. Methods This multicenter study included patients with NAFLD without a history of SARS-CoV-2 infection. All patients were vaccinated with 2 doses of inactivated vaccine against SARS-CoV-2. The primary safety outcome was the incidence of adverse reactions within 7 days after each injection and overall incidence of adverse reactions within 28 days, and the primary immunogenicity outcome was neutralizing antibody response at least 14 days after the whole-course vaccination. Results A total of 381 patients with pre-existing NAFLD were included from 11 designated centers in China. The median age was 39.0 years (IQR 33.0–48.0 years) and 179 (47.0%) were male. The median BMI was 26.1 kg/m 2 (IQR 23.8–28.1 kg/m 2 ). The number of adverse reactions within 7 days after each injection and adverse reactions within 28 days totaled 95 (24.9%) and 112 (29.4%), respectively. The most common adverse reactions were injection site pain in 70 (18.4%), followed by muscle pain in 21 (5.5%), and headache in 20 (5.2%). All adverse reactions were mild and self-limiting, and no grade 3 adverse reactions were recorded. Notably, neutralizing antibodies against SARS-CoV-2 were detected in 364 (95.5%) patients with NAFLD. The median neutralizing antibody titer was 32 (IQR 8-64), and the neutralizing antibody titers were maintained. Conclusions The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in patients with NAFLD. Lay summary The development of vaccines against coronavirus disease 2019 (COVID-19) has progressed rapidly, with encouraging safety and efficacy data. This study now shows that the inactivated COVID-19 vaccine appears to be safe with good immunogenicity in the large population of patients with non-alcoholic fatty liver disease.

Unmutated tumor antigens are chosen as primary candidates for tumor vaccine because of their expression on multiple lineages of tumors. A critical issue is whether unmutated tumor antigens are expressed in normal cells, and if so, whether such expression imposes special restrictions on cytotoxic T lymphocyte (CTL) responses. In this study, we use a transgenic approach to study the development and effector function of T cells specific for P1A, a prototypical unmutated tumor antigen. We report here that although P1A is expressed at low levels in normal tissues, including lymphoid tissues, the P1A-specific transgenic T cells develop normally and remain highly responsive to the P1A antigen. The fact that transgenic expression of P1A antigen in the thymus induces T cell clonal deletion demonstrates that normal hematopoietic cells can process and present the P1A antigen and that P1A-specific T cells are susceptible to clonal deletion. By inference, P1A-specific T cells must have escaped clonal deletion due to low expression of P1A in the thymus. Interestingly, despite the fact that an overwhelming majority of T cells in the T cell receptor for antigen (TCR)–transgenic mice are specific for P1A, these mice are no more resistant to a P1A-expressing plasmocytoma than nontransgenic littermates. Moreover, when the same TCR-transgenic mice were challenged simultaneously with B7-1+ and B7-1− tumors, only B7-1+ tumors were rejected. Therefore, even though P1A can be a tumor rejection antigen, the effector function of P1A-specific CTL is restrained in vivo. These results have important implications for the strategy of tumor immunotherapy.

BackgroundMarek's disease (MD) is an economically important viral disease of chickens caused by Marek's disease virus (MDV), an oncogenic herpesvirus. This disease was well controlled since the widespread use of commercial vaccines, but field MDVs have shown continuous increasing in virulence and acquired the ability to overcome the immune response induced by vaccines. Nowadays, MD continues to be a serious threat to poultry industry, isolation and characterization of MDVs are essential for monitoring changes of viruses and evaluating the effectiveness of existing vaccines.ResultsBetween 2008 and 2010, 18 field MDV strains were isolated from vaccinated chicken flocks in Sichuan province, China. Three oncogenic genes including Meq, pp38 and vIL-8 genes of the 18 isolates were amplified and sequenced. Homology analysis showed that the deduced amino acid sequences of these three genes exhibit 95.0-98.8%, 99.3-100% and 97.0-98.5% homology respectively with these of other reference strains published in GenBank. Alignment analysis of the nucleotide and deduced amino acid sequences showed that four amino acid mutations in Meq gene and two amino acid mutations in vIL-8 gene displayed perfect regularity in MDVs circulating in China, which could be considered as features of field MDVs prevalent in recent years in China. In addition, one amino acid mutation in pp38 gene can be considered as a feature of virulent MDVs from USA, and three amino acid mutations in Meq gene were identified and unique in very virulent plus (vv+) MDVs. Phylogenetic analysis based on Meq and vIL-8 protein sequences revealed that field MDVs in China evolved independently. Virulence studies showed that CVI988 could provide efficient protection against the field MDVs epidemic recently in China.ConclusionsThis study and other published data in the GenBank have demonstrated the features of Meq, pp38 and vIL-8 genes of MDVs circulating in recent years in Sichuan, China. Mutations, deletions or insertions were observed in these three genes, and some mutations could be considered as the unique marks of the MDVs circulating presently in China. The paper supplies some valuable information concerning the evolution of MDV which is useful for the vaccine development and control of MD in China.