Viral immunology最新文献

Coronavirus Disease 2019 (COVID-19) is generally susceptible to the population, highly infectious, rapidly transmitted, and highly fatal. There is a lack of specific drugs against the virus at present and vaccination is the most effective strategy to prevent infection. However, studies have found that some groups, particularly patients with diabetes, show varying degrees of weak immune reactivity to various COVID-19 vaccines, resulting in poor preventive efficacy against the novel coronavirus in patients with diabetes. Therefore, in this study, patients with type 2 diabetes mellitus (T2DM) who had weak immune response to the COVID-19 vaccine in recent years were analyzed. This article reviews the phenomenon, preliminary mechanism, and related factors affecting weak vaccine response in patients with T2DM, which is expected to help in the development of new vaccines for high-risk groups for COVID-19.

Hepatitis B virus (HBV) is a global public health concern, and China continues to face a high burden of HBV cases. Vaccination plays a critical role in controlling and eradicating HBV. However, studies have shown that some individuals may experience waning immunity over time, highlighting the importance of enhanced immunization strategies. This study aimed to investigate the relationship between age, gender, and anti-HBs antibody levels, as well as the prevalence of serum hepatitis B surface antigen (HBsAg)/HBV e antigen (HBeAg) positivity. This retrospective study included 43,609 pediatric patients who visited the outpatient department between January 2013 and December 2022. Serum biomarkers (HBsAg, anti-HBs, HBeAg, anti-HBe, and anti-HBc) were measured using Roche Cobas 8000. There is a significant difference in anti-HBs titer between genders and across different age groups (p < 0.05). The serological markers HBsAg/HBeAg exhibited the highest positivity rate in the age group of 15-18 years. The findings demonstrate a gradual decrease in anti-HBs levels following HBV vaccination. The prevalence of serum markers HBsAg/HBeAg is higher among adolescents aged 15-18 years, which should be a matter of concern and attention.

Kyasanur Forest Disease Virus (KFDV) is a tick-borne flavivirus that causes life-threatening hemorrhagic fever in humans with case fatality rates of 3-5%. Relatively little is known about the mechanism of its pathogenesis or host immune responses to KFDV infection. Here, we investigated KFDV-specific cellular immune responses in the recovered cases of Kyasanur Forest Disease (KFD). Peripheral blood mononuclear cells of the recovered KFD cases and healthy controls were exposed to γ-inactivated KFDV antigen ex vivo. The proliferation index was determined using an enzyme-linked immunosorbent assay-based lymphoproliferative assay. The frequencies of CD4⁺ and CD8⁺ T cells expressing intracellular interferon (IFN)-γ in response to stimulation with γ-inactivated KFDV antigen were determined using flow cytometry. A significant increase in lymphoproliferation and a high frequency of CD4⁺ and CD8⁺ T cells secreting IFN-γ against γ-inactivated KFDV antigen were found in the recovered KFD group compared to the healthy control group. In conclusion, the study indicated the generation of cellular immune responses in individuals who recovered from KFD and can be used as indicators of cellular immunity in KFD vaccine studies.

The respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in children and poses a significant risk to older adults. Developing a vaccine against RSV has been a priority, and the recently approved Arexvy vaccine has shown promise in preventing lower respiratory tract disease (LRTD) caused by RSV in individuals aged 60 years and older. This comprehensive review discusses the history of RSV, challenges in vaccine development, and the mechanism of action of Arexvy. The efficacy and safety of the vaccine are explored based on phase 3 clinical trial, demonstrating its effectiveness in preventing RSV-associated LRTD. The most common adverse reactions reported include injection site pain, fatigue, myalgia, headache, and arthralgia. Ongoing research focuses on the long-term effectiveness of Arexvy, including the need for booster doses and its impact on reducing RSV-associated hospitalizations. The potential of Arexvy to lessen the burden of RSV-related illnesses, particularly in vulnerable populations, is highlighted, emphasizing the importance of widespread immunization efforts and accessibility to this groundbreaking vaccine.

Hantaan virus (HTNV) is prevalent in Eurasia. It causes hemorrhagic fever with renal syndrome (HFRS). Long noncoding RNAs (lncRNAs) play key roles in regulating innate immunity. Among these, lncRNA negative regulator of interferon response (NRIR) was reported as an inhibitor of several interferon (IFN)-stimulated genes. Our results showed that: NRIR expression was upregulated by HTNV infection in a type I IFN-dependent manner. The expression of NRIR in CD14⁺ monocytes from HFRS patients in acute phase was significantly higher than that in convalescent phase and healthy controls. HTNV infection in some HTNV-compatible cells was promoted by NRIR. NRIR negatively regulated innate immunity, especially IFITM3 expression. Localized in the nucleus, NRIR bound with HNRNPC, and knockdown of HNRNPC significantly weakened the effect of NRIR in promoting HTNV infection and restored IFITM3 expression. These results indicated that NRIR regulates the innate immune response against HTNV infection possibly through its interaction with HNRNPC and its influence on IFITM3.

The inactivated whole-virion severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine has been widely used in a two-dose schedule, but with insufficient data on the immunogenicity of homologous BBIBP-CorV/CoronaVac boosting vaccination and too little follow-up to assess the duration of the immunogenic response. We prospectively evaluated the immunogenicity of a third-dose BBIBP-CorV/CoronaVac boosting vaccination, with neutralizing titers against wild type and Omicron assessed at the baseline (immediately before the booster dose), and days 14, 28, 98, and 174 post the third-booster. Of 182 volunteers screened, 165 were assessed eligible for enrolment. No moderate/severe adverse events were observed during the term of the study. From the baseline to day 174 post the third booster, neutralizing titers against wild type and Omicron peaked by approximately sixfold increase (up to 811.83 and 33.40, respectively) at day 14 and slowly decreased over time. The geometric mean titers against Omicron were lower than against type with a 19.8-39. Sixfold reduction at all time points. The seropositivity against Omicron at the baseline, days 14, 28, 98, and 174 after the booster dose was 12.6%, 50.0%, 37.8%, 38.6%, and 22.8%, respectively. Data presented herein indicated that the BBIBP-CorV/CoronaVac booster significantly enhances the neutralizing potency against wild-type strain but elicited weaker neutralizing activity to Omicron. Our findings suggest that individuals receiving booster inactivated vaccine remain at risk for Omicron infection, which is crucial to inform ongoing and future vaccination strategies to combat coronavirus disease 2019.

Numerous studies have highlighted the emergence of coronavirus disease (COVID-19) symptoms reminiscent of Kawasaki disease in children, including fever, heightened multisystem inflammation, and multiorgan involvement, posing a life-threatening complication. Consequently, extensive research endeavors in pediatric have aimed to elucidate the intricate relationship between COVID-19 infection and the immune system. COVID-19 profoundly impacts immune cells, culminating in a cytokine storm that particularly inflicts damage on the pulmonary system. The gravity and vulnerability to COVID-19 are closely intertwined with the vigor of the immune response. In this context, the human leukocyte antigen (HLA) molecule assumes pivotal significance in shaping immune responses. Genetic scrutiny of HLA has unveiled the presence of at least one deleterious allele in children afflicted with multisystem inflammatory syndrome in children (MIS-C). Furthermore, research has demonstrated that COVID-19 exploits the angiotensin-converting enzyme 2 (ACE-2) receptor, transmembrane serine protease type 2, and various other genes to gain entry into host cells, with individuals harboring ACE-2 polymorphisms being at higher risk. Pediatric studies have employed diverse genetic methodologies, such as genome-wide association studies (GWAS) and whole exome sequencing, to scrutinize target genes. These investigations have pinpointed two specific genomic loci linked to the severity and susceptibility of COVID-19, with the HLA locus emerging as a notable risk factor. In this comprehensive review article, we endeavor to assess the available evidence and consolidate data, offering insights into current clinical practices and delineating avenues for future research. Our objective is to advance early diagnosis, stabilization, and appropriate management strategies to mitigate genetic susceptibility's impact on the incidence of COVID-19 in pediatric patients with multisystem inflammation.

Interleukin-36 (IL-36) signaling plays an important role in promoting CD8⁺ T cell-mediated antitumor immune responses. The role of IL-36 signaling in CD8⁺ T cells that are involved in host immune responses during human immunodeficiency virus-1 (HIV-1) infection has not been characterized. Sixty-one patients living with chronic HIV-1 infection and 23 controls were enrolled in this study. The levels of IL-36 cytokine family members were measured by enzyme-linked immunosorbent assay. Purified CD8⁺ T cells were stimulated with recombinant IL-36gamma (1 or 10 ng/mL). The expression of inhibitory receptors, the secretion of cytotoxic molecules and interferon-gamma, and the mRNA levels of apoptosis-related ligands were assessed to evaluate the effect of IL-36gamma on CD8⁺ T cell function in vitro. There were no significant differences in IL-36alpha, IL-36beta, or IL-36 receptor antagonist levels between patients living with chronic HIV-1 infection and controls. Plasma IL-36gamma levels were reduced in patients living with chronic HIV-1 infection. Perforin, granzyme B, and granulysin secretion, as well as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL) mRNA expression, but not programmed death-1 (PD-1) or cytotoxic T lymphocyte-associated protein-4 (CTLA-4) expression was downregulated in CD8⁺ T cells from patients living with chronic HIV-1 infection. The addition of both 1 and 10 ng/mL IL-36gamma enhanced perforin, granzyme B, granulysin, and interferon-gamma secretion by CD8⁺ T cells without affecting PD-1/CTLA-4 or TRAIL/FasL mRNA expression in CD8⁺ T cells from patients living with chronic HIV-1 infection. The addition of 1 ng/mL IL-36gamma also promoted perforin and granzyme B secretion by HIV-1-specific CD8⁺ T cells from patients living with chronic HIV-1 infection. The reduced IL-36gamma levels in patients living with chronic HIV-1 infection might be insufficient for the activation of CD8⁺ T cells, leading to CD8⁺ T cell exhaustion.

Human papillomavirus (HPV) infections are common, transmitted by sexual and nonsexual routes. The present case-control setting was designed to examine potential cofactors associated with either persistently low or high HPV-antibody levels. The study subjects were from the Finnish HPV Family cohort of 329 baseline pregnant, non-HPV-vaccinated women, who were sampled for genital and oral HPV-DNA and HPV serology at baseline, and at 12, 24, and 36 months. Antibodies to the L1 major capsid protein of HPV 6, 11, 16, 18, and 45 were analyzed by multiplex HPV serology and HPV genotyping was performed. This study included 59 women, 23 women with persistently low (<200 median fluorescence intensity [MFI]) and 36 women with persistently high and always positive (>200 MFI) levels of these antibodies for all five HPV genotypes. Potential HPV-associated covariates were derived from detailed questionnaires. Only cofactors other than detected HPV genotype significantly impact on the levels of natural HPV antibodies. A higher number of past sexual partners or a history of diagnosed genital warts were significant covariates of high HPV antibody levels (p = 0.023 and p = 0.043, respectively). Of interest, women with a history of allergies presented with low levels of HPV antibodies (p = 0.03), potentially exposing these women to an increased risk of future HPV-related diseases that merit closer surveillance.