Viral immunology最新文献

Hepatitis B virus (HBV) infection is a major health problem worldwide and causes almost one million deaths annually. The HBV core gene codes for two related antigens, known as core antigen (HBcAg) and e-antigen (HBeAg), sharing 149 residues but having different amino- and carboxy-terminals. HBeAg is a soluble variant of HBcAg and a clinical marker for determining the disease severity and patients' screening. Currently available HBeAg assays have a shortcoming of showing cross-reactivity with HBcAg. In this study, for the first time, we evaluated whether HBcAg-adsorbed anti-HBe polyclonal antibodies could specifically recognize HBeAg or still show cross-reactivity with HBcAg. Recombinant HBeAg was cloned in pCold1 vector and successfully expressed in Escherichia coli and after purification by Ni-NTA resin was used to generate polyclonal anti-HBe antibodies in rabbit. Purified HBeAg was further characterized by assessing its reactivity with anti-HBe in the sera of chronically infected patients and HBeAg-immunized rabbit. Sera from patients with chronic HBV infection, containing anti-HBe, specifically reacted with recombinant HBeAg, implying antigenic similarity between the prokaryotic and native HBeAg in the serum of HBV-infected patients. In addition, the designed enzyme-linked immunosorbent assay (ELISA) with rabbit anti-HBe polyclonal antibodies could detect recombinant HBeAg with high sensitivity, while high cross-reactivity with HBcAg was observed. It is noteworthy that HBcAg-adsorbed anti-HBe polyclonal antibodies still showed high cross-reactivity with HBcAg, implying that due to the presence of highly similar epitopes in both antigens, HBcAg-adsorbed polyclonal antibodies cannot differentiate between the two antigens.

Despite the great success of vaccines in various infectious diseases, most current vaccines are not effective enough, and on the contrary, clinically approved alum adjuvants cannot induce sufficient immune responses, including a potent cellular immune response to confer protection. In this study, we used Nanochelating Technology to develop novel nanoadjuvants to boost the potency of the alum-adjuvanted inactivated severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine. BALB/c mice were immunized twice over 2 weeks with different doses of adjuvanted-vaccine formulations and immune responses were assessed. The analysis results of IFN-γ and IL-17 cytokines demonstrated the effectiveness of the nanoadjuvants produced by the Nanochelating Technology in shifting the alum-based vaccine toward a stronger Th1 pattern. In addition, these nanoadjuvants improved IL-2 cytokine response, which shows the efficacy of these novel formulations in inducing specific T lymphocyte proliferation. Using these nanoadjuvants increased IL-10 cytokine secretion that may be representative of a better immunoregulatory impact and may also potentially prevent immunopathology responses. Moreover, specific IgG titer analysis revealed the potency of these nanoadjuvants in improving humoral immune responses. The enzyme-linked immunosorbent assay of receptor-binding domain (RBD)-specific IgG response showed that the developed novel formulations induced strong IgG responses against this protein. This study shows that the nanostructures produced by the Advanced Nanochelating Technology have potent adjuvant effects on alum-based SARS-CoV-2 vaccines to not only compensate for alum weakness in inducing the cellular immune responses by smart regulation of the immune system but also significantly improve the humoral and cellular immune responses simultaneously.

In this study, we reported the expression and potency of the recombinant H1N1 hemagglutinin (HA) vaccine as our in-house vaccine in a BALB/c mouse model. Recombinant H1N1 HA was produced in SF9 cell line, purified and formulated in MF59 adjuvant. Experimental mice were injected on days 0 and 14 with MF59-formulated vaccine, alum-based vaccine, and phosphate-buffered saline (PBS). Interleukin (IL)-2, IL-4, and interferon (IFN)-γ were assessed with commercial enzyme-linked immunosorbent assay (ELISA). Antibody responses and cytotoxic T lymphocyte (CTL) activity were assessed by hemagglutination inhibition and granzyme B ELISA, respectively. Moreover, the mice were challenged to show the vaccine efficacy. A considerable rise in IFN-γ and IL-4, as well as IFN-γ/IL-4 ratio, was observed in comparison with the alum-based vaccine and PBS group. Furthermore, our candidate vaccine showed superiority in humoral immune responses and CTL activity versus the alum-based vaccine and PBS group. The challenge showed that the survival rate in the vaccinated groups revealed a significant increase as compared with that in the PBS group. In conclusion, our candidate vaccine showed a robust Th1 response and CTL activity the alum-based vaccine. Moreover, a significant humoral immune response and a higher survival rate were detected in our vaccine as compared with the alum-based vaccine. It seems that the superiority of the MF59-based vaccine is due to the type of vaccine formulation in the candidate vaccine.

We determined anti-rubella and anti-measles immunoglobulin G (IgG) in 7- to 19-year-old children and adolescents with vaccine only-induced immunity of Córdoba, Argentina, during a 6-month period over 2021-2022. Of the 180 individuals studied, 92.2% and 88.3% were positive for anti-measles and anti-rubella IgG, respectively. No significant differences were found comparing anti-rubella IgG concentrations (p = 0.144) and anti-measles IgG concentrations (p = 0.105) of individuals classified by age, but anti-measles IgG and anti-rubella IgG levels were significantly higher among female individuals compared with males (p = 0.031 and p = 0.036, respectively). Female subjects in the younger age group had higher concentrations of anti-rubella IgG as well (p = 0.020), even when anti-measles IgG concentrations did not differ among female age-subgroups (p = 0.187). In contrast, age subgroups of male individuals did not have significantly different IgG concentrations for rubella (p = 0.745) or measles (p = 0.124). Among samples with discordant results (22/180, 12.6%), 9.1% were negative for rubella but positive for measles; 13.6% were equivocal for rubella and positive for measles; 22.7% were equivocal for rubella and negative for measles, while 54.5% were positive for rubella but negative for measles. The findings indicate a seroprevalence below recommended for preventing measles in the population studied, while they evidence the need for standardization of serological tests for rubella IgG.

This study aims to analyze the achievements of coronavirus disease-2019 (COVID-19) vaccination in five provinces in Indonesia, North Maluku, West Sulawesi, Maluku, West Papua, and Papua. Furthermore, to establish herd immunity in the new normal perspective. Vaccination is important because it is an effective way to build immunity. This method uses qualitative research with a Qualitative Data Analysis Software (QDAS) approach. The source of data was obtained from the official website of the government, the ministry of health, in the category of areas with low vaccination achievement, and data were also obtained by capturing news in credible official media to find the cause of the low vaccination rate in the community. The data analyst uses NVivo12 software to code and visualizes data in graphs, images, and word clouds. The findings of this study indicate that in five provinces in Indonesia, North Maluku (68%), West Sulawesi (76%), Maluku (66%), West Papua (62%), and Papua (41%), the achievement of vaccination implementation is still relatively low. Due to doubts in the community about the status of the vaccine, information and communication education from the government have not been optimal; the environment and geography vary, so it becomes an obstacle in carrying out vaccination.

Few data are available on the impact of COVID-19 vaccination on CD4 counts and HIV-RNA in persons living with HIV (PLWH). We present the data of 235 PLWH who were vaccinated with BNT162b2 in March 2021-February 2022 at the "Cotugno" hospital in Naples. PLWH treated at the "Cotugno" hospital, who were vaccinated at the hospital vaccination center, without prior COVID-19 and for whom immunological/virological data were available in the last 12 months and in the 6 months after vaccination were included. Antispike Ab were available for 187 and 64 PLWH after the second and third doses: PLWH with antispikes >33 binding antibodies units (BAU)/mL increased from 91% to 98%. Antinucleocapsid Ab performed in 147 and 56 patients identified 19 (13%) asymptomatic/paucisymptomatic COVID-19 infections after the second dose and an additional 15 (27%) after the third dose. Immunological/virological data were collected before vaccination (T0), after the second dose (T1), and after the third dose (T2). The absolute number of CD4 increased after the third dose (median 663, 657, and 707 at T0, T1, and T2; p < 0.000 T0 vs. T2). The proportion of patients with HIV-RNA <50 copies/mL increases significantly after the second dose (73%; 85.7%; 87.7%; p < 0.000 T0 vs. T2). The presence of COVID-19 asymptomatic/paucisymptomatic infections (demonstrated by the presence of antinucleocapsid Ab) significantly increases SARS-CoV-2 antispike Ab after second dose, but not after third dose. Asymptomatic/paucisymptomatic COVID-19 infections do not have influence on CD4 cell number and HIV-RNA level. Similarly, the presence of not-controlled HIV-RNA (HIV-RNA >50 copies/mL) does not influence antispike Ab response. According to our data, the response to SARS-CoV2 vaccination is effective in people living with HIV. Vaccination against COVID-19 appears to positively affect immunological and virological levels in people living with HIV.

Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly resulted in a pandemic constituting a global health emergency. As an indicator of long-term immune protection from reinfection with the SARS-CoV-2 virus, the presence of memory B cells (MBCs) should be evaluated. Since the beginning of COVID-19 pandemic, several variants of concerns have been detected, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1/B.1.1.28.1), Delta (B.1.617.2), and Omicron (BA.1) variants with several different mutations, causing serious concern regarding the increased frequency of reinfection, and limiting the effectiveness of the vaccine response. At this regard, we investigated SARS-CoV-2-specific cellular immune responses in four different cohorts: COVID-19, COVID-19 infected and vaccinated, vaccinated, and negative subjects. We found that MBC response to SARS-CoV-2 at more than 11 months postinfection was higher in the peripheral blood of all COVID-19 infected and vaccinated subjects respect to all the other groups. Moreover, to better characterize the differences of SARS-CoV-2 variants immune responses, we genotyped SARS-CoV-2-positive samples from the patients' cohort. We found a higher level of immunoglobulin M+ (IgM+) and IgG+ spike MBCs in SARS-CoV-2-positive patients (5-8 months after symptoms onset) infected with the SARS-CoV-2-Delta variant compared with the SARS-CoV-2-Omicron variant implying a higher immune memory response. Our findings showed that MBCs persist more than 11 months after primary infection indicating a different involvement of the immune system according to the different SARS-CoV-2 variant that infected the host.

FcγR is expressed by many immune cells and plays an important role in the immune response to hepatitis B virus (HBV) infection. CD32 belongs to the FcγR family. This study aimed to observe changes in CD32 expression by CD4⁺ T and CD8⁺ T lymphocytes in chronic HBV infection patients and evaluate the clinical utility of CD4⁺ T and CD8⁺ T CD32 expression to assess the severity of liver injury in chronic HBV-infected patients. A total of 68 chronic HBV patients and 40 healthy individuals were recruited, and the median fluorescence intensity (MFI) of CD32 expression on CD4⁺ T, CD8⁺ T lymphocytes was measured using flow cytometry and the CD4⁺ T, CD8⁺ T CD32 index was calculated. The reactivity of the healthy individual lymphocytes to mixed patients' plasma containing HBV was observed. Finally, the correlation between CD4⁺ T, CD8⁺ T lymphocytes CD32 MFI and liver function indicator levels was analyzed. The CD4⁺ T, CD8⁺ T CD32 MFI and index were significantly elevated in HBV patient groups than in normal control group (p < 0.001, for all). Furthermore, the CD32 MFI of healthy persons' CD4⁺ T and CD8⁺ T lymphocytes were remarkably increased when stimulated with mixed patients' plasma containing high HBV copies (p < 0.001; P < 0.001). More importantly, in HBV patients, there was a significant positive correlation between CD4⁺ T, CD8⁺ T CD32 MFI and the level of serum aspartate aminotransferase (p < 0.05, p < 0.05). In conclusion, the increased expression of CD32 on CD4⁺ T and CD8⁺ T lymphocytes might be potential promising biomarkers for the severity of liver function impairment in chronic HBV patients.