Live attenuated vaccine(United States Army Medical Research Institute of Infectious Diseases)

Vaccination against preventable infections is important for the management of rheumatic diseases (RDs). This study assessed the vaccination coverage and predictors among patients with RDs using real-world data from Israel.

This retrospective cross-sectional study, based on a Maccabi Healthcare Services database, included adult patients diagnosed with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and systemic lupus erythematosus (SLE), as of April 30, 2019. Age-specific vaccination coverage for influenza (past year), pneumococcal (23-valent pneumococcal polysaccharide vaccine [PPSV23] and/or 13-valent pneumococcal conjugate vaccine [PCV13]), and live-attenuated herpes zoster (HZ) vaccines (past 5 years) was reported. Logistic regression was used to investigate predictors of vaccination.

The study included 14,528 patients (RA: n = 6932; PsA: n = 4395; SLE: n = 1951; > 1 condition: n = 1250). Influenza vaccine coverage among patients with RA, PsA, and SLE was 45.1%, 36.2%, and 33.7%, respectively. For PPSV23, corresponding rates were 19.6%, 16.2%, and 12.6%, respectively. In the elderly population (≥ 65 years), 63.2% had influenza vaccine in the past year and 83.4% had a PPSV23 vaccine in the past 5 years or at age ≥ 65. For PCV13 and HZ, coverage in the overall study population was low at 4.8% and 3.6%, respectively. Central residence and treatment with corticosteroids and biologic or targeted synthetic disease-modifying antirheumatic drugs within the past 5 years were significant predictors of vaccination coverage across all vaccines (P< 0.05). Other predictors varied by vaccine, including female sex (influenza, PPSV23, PCV13), age (influenza, PPSV23), chronic comorbidities (influenza, PPSV23, PCV13), shorter disease duration (PCV13), and high socioeconomic status (PCV13, HZ).

This study demonstrated suboptimal coverage of influenza, pneumococcal, and HZ vaccination in patients with RA, PsA, and SLE, in particular among younger adults in Israel.

Type I interferon (IFN)-mediated responses operate a pivotal role in the first line of host immune defense against viruses. Upon DNA virus infection, DNA sensing cyclic GMP-AMP synthase-STING signal pathway is a key event in the IFN-mediated antiviral response and also a target of viral immune evasion. African swine fever (ASF) is a highly contagious, cross-border viral disease that often confers fatalities in domestic and feral pigs of all ages. African swine fever virus (ASFV), a causative agent of ASF, is a nucleocytoplasmic large DNA virus that masks critical elements of host immune system by several encoded proteins. In this study, we report a novel immune evasion mechanism of ASFV B175L to block type I IFN signaling by targeting STING and 2'3'-cyclic GMP-AMP (2′3′-cGAMP). We found that ASFV B175L significantly inhibited the DNA virus-induced IFN-β production and IFN-mediated signaling responses. The conserved zf-FCS motif of ASFV B175L competitively interacted with both cGAMP and the cyclic dinucleotide binding domain of STING. Remarkably, the R238 and Y240 amino acids of STING were crucial for interaction with ASFV B175L. Consequently, this interaction inhibits the interaction between cGAMP and STING, thereby inhibiting downstream signaling including STING polymerization and phosphorylation of TANK-binding kinase 1 and interferon regulatory factor 3 for antiviral signaling. Taken together, these results highlight the critical role of ASFV B175L in suppression of IFN responses and provide a new target to guide live-attenuated ASFV vaccine.

African swine fever virus (ASFV), the only known DNA arbovirus, is the causative agent of African swine fever (ASF), an acutely contagious disease in pigs. ASF has recently become a crisis in the pig industry in recent years, but there are no commercially available vaccines. Studying the immune evasion mechanisms of ASFV proteins is important for the understanding the pathogenesis of ASFV and essential information for the development of an effective live-attenuated ASFV vaccines. Here, we identified ASFV B175L, previously uncharacterized proteins that inhibit type I interferon signaling by targeting STING and 2′3′-cGAMP. The conserved B175L-zf-FCS motif specifically interacted with both cGAMP and the R238 and Y240 amino acids of STING. Consequently, this interaction interferes with the interaction of cGAMP and STING, thereby inhibiting downstream signaling of IFN-mediated antiviral responses. This novel mechanism of B175L opens a new avenue as one of the ASFV virulent genes that can contribute to the advancement of ASFV live-attenuated vaccines.