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1.
《Vaccine》2021,39(15):2110-2116
The success of SARS-CoV-2 (CoV-2) vaccines is measured by their ability to mount immune memory responses that are long-lasting. To achieve this goal, it is important to identify surrogates of immune protection, namely, CoV-2 MHC Class I and II immunodominant pieces/epitopes and methodologies to measure them. Here, we present results of flow cytometry-based MHC Class I and II QuickSwitchTM platforms for assessing SARS-CoV-2 peptide binding affinities to various human alleles as well as the H-2 Kb mouse allele. Multiple SARS-CoV-2 potential MHC binders were screened and validated by QuickSwitch testing. The screen included 31 MHC Class I and 19 MHC Class II peptides predicted to be good binders by the IEDB web resource provided by NIAID. While several predicted peptides with acceptable theoretical Kd showed poor MHC occupancies, fourteen MHC class II and three MHC class I peptides showed promiscuity in that they bind to multiple MHC molecule types. In addition to providing important data towards the study of the SARS-CoV-2 virus and its presented antigenic epitopes, the peptides identified in this study can be used in the QuickSwitch platform to generate MHC tetramers. With those tetramers, scientists can assess CD4 + and CD8 + immune responses to these different MHC/peptide complexes.  相似文献   

2.
Li X  Miao H  Henn A  Topham DJ  Wu H  Zand MS  Mosmann TR 《Vaccine》2012,30(31):4581-4584
Although previous studies have found minimal changes in CD4 T cell responses after vaccination of adults with trivalent inactivated influenza vaccine, daily sampling and monitoring of the proliferation marker Ki-67 have now been used to reveal that a substantial fraction of influenza-specific CD4 T cells respond to vaccination. At 4-6 days after vaccination, there is a sharp rise in the numbers of Ki-67-expressing PBMC that produce IFNγ, IL-2 and/or TNFα in vitro in response to influenza vaccine or peptide. Ki-67(+) cell numbers then decline rapidly, and 10 days after vaccination, both Ki-67(+) and overall influenza-specific cell numbers are similar to pre-vaccination levels. These results provide a tool for assessing the quality and quantity of CD4 T cell responses to different influenza vaccines, and raise the possibility that the anti-influenza T cell memory response may be qualitatively altered by vaccination, even if the overall memory cell numbers do not change significantly.  相似文献   

3.
《Vaccine》2022,40(12):1755-1760
ObjectivesHealthcare workers (HCWs) are a priority group for seasonal influenza vaccination (SIV). The 2020/21 SIV campaign was conducted during the second wave of the COVID-19 pandemic. Vaccines, including SIV, may exert non-specific protective effects on other infectious diseases which may be ascribable to the concept of trained immunity. The aim of this study was to explore the association between 2020/21 SIV and SARS-CoV-2 positivity in a cohort of Italian HCWs.MethodsIn this observational study, a cohort of HCWs employed by a large (ca 5000 employees) referral tertiary acute-care university hospital was followed up retrospectively until the start of the COVID-19 vaccination campaign. The independent variable of interest was the 2020/21 SIV uptake. Both egg-based and cell culture-derived quadrivalent SIVs were available. The study outcome was the incidence of new SARS-CoV-2 infections, as determined by RT-PCR. Multivariable Cox regression was applied in order to discern the association of interest.ResultsThe final cohort consisted of 2561 HCWs who underwent ≥1 RT-PCR test and accounted for a total of 94,445 person-days of observation. SIV uptake was 35.6%. During the study period, a total of 290 new SARS-CoV-2 infections occurred. The incidence of new SARS-CoV-2 was 1.62 (95% CI: 1.22–2.10) and 3.91 (95% CI: 3.43–4.45) per 1000 person-days in vaccinated and non-vaccinated HCWs, respectively, with an adjusted non-proportional hazard ratio of 0.37 (95% CI: 0.22–0.62). E-values suggested that unmeasured confounding was unlikely to explain the association.ConclusionsA lower risk of SARS-CoV-2 infection was observed among SIV recipients.  相似文献   

4.
《Vaccine》2023,41(22):3403-3409
We examined whether the second monovalent SARS-CoV-2 mRNA booster increased antibody levels and their neutralizing activity to Omicron variants in nursing home residents (NH) residents and healthcare workers (HCW). We sampled 376 NH residents and 63 HCW after primary mRNA vaccination, first and second boosters, for antibody response and pseudovirus neutralization assay against SARS-CoV-2 wild-type (WT) (Wuhan-Hu-1) strain, Omicron BA.1 and BA.5 variants. Antibody levels and neutralizing activity progressively increased with each booster but subsequently waned over 3–6 months. NH residents, both those without and with prior infection, had a robust geometric mean fold rise (GMFR) of 8.1 (95% CI 4.4, 14.8) and 7.8 (95% CI 4.8, 12.9) respectively in Omicron-BA.1 subvariant specific neutralizing antibody levels following the second booster vaccination (p < 0.001). These results support the ongoing efforts to ensure that both NH residents and HCW are up-to-date on recommended SARS-CoV-2 vaccine booster doses.  相似文献   

5.
[摘要] 目的 探讨新型冠状病毒肺炎(coronavirus disease 2019, COVID-19)无症状感染者的临床和免疫学特征。方法 选取2020年1月22日—6月22日石家庄市第五医院收治的59例COVID-19患者作为研究对象,分析不同疾病分期患者的临床资料。利用流式细胞术检测患者外周血T淋巴细胞亚群计数,Procarta Plex多细胞因子检测系统检测外周血25种细胞因子和9种趋化因子水平。结果 59例COVID-19患者中,无症状感染组28例(47.5%)、轻型组6例(10.2%)、普通型组19例(32.2%),重型/危重型组6例(10.2%)。无症状感染组中位年龄为23.0(19.3,34.8)岁,显著低于普通型组的35.0(24.0,52.0)岁和重型/危重型组的64.5(52.0,68.3)岁(P均<0.05)。无症状感染组患者较少患有基础疾病,均无症状、体征和胸部CT变化,其外周血CD3+ T细胞、CD4+ T细胞、CD8+ T细胞计数均显著高于重型/危重型组(P均<0.05),同时CD4+ T细胞计数显著高于普通型组(P<0.05)。14例无症状感染组患者治疗前与治疗后CD3+ T细胞、CD4+ T细胞和CD8+ T细胞计数比较,差异均无统计学意义(P均>0.05)。14例无症状感染组患者治疗前后CD4+ T细胞计数的变化幅度均显著低于普通型组、重型/危重型组(P均<0.05)。无症状感染组外周血可检测到11种细胞因子和趋化因子,其中IL-7水平显著高于对照组, IP-10水平均显著低于普通型组、重型/危重型组,差异均具有统计学意义(P均<0.05)。结论 COVID-19无症状感染者以青年为主,但未发现与性别因素相关。随着COVID-19病情进展,普通型、重型/危重型患者外周血T细胞亚群计数降低,而细胞因子和趋化因子水平升高,但上述指标在无症状感染者中未见显著改变。  相似文献   

6.
《Vaccine》2021,39(35):5055-5063
ObjectiveTo assess the value of using SARS-CoV-2 specific antibody testing to prioritize the vaccination of susceptible individuals as part of a COVID-19 vaccine distribution plan when vaccine supply is limited.MethodsAn extended susceptible-infected-recovered (SIR) compartmental model was used to simulate COVID-19 spread when considering diagnosis, isolation, and vaccination of a cohort of 1 million individuals. The scenarios modeled represented 4 pandemic severity scenarios and various times when the vaccine becomes available during the pandemic. Eligible individuals have a probability p of receiving antibody testing prior to vaccination (p = 0, 0.25, 0.5, 0.75, and 1). The vaccine was modeled as a single dose vaccine with 90% and 70% efficacy. The value of serology testing was evaluated by comparing the infection attack rate, peak infections, peak day, and deaths.ResultsThe use of antibody testing to prioritize the allocation of limited vaccines reduces infection attack rates and deaths. The size of the reduction depends on when the vaccine becomes available relative to the infection peak day. The largest percentage reduction in cases and deaths occurs when the vaccine is deployed before and close to the infection peak day. The reduction in the number of cases and deaths diminishes as vaccine deployment is delayed.ConclusionsAntibody testing as part of the vaccination plan is an effective method to maximize the benefit of a COVID-19 vaccine. Decision-makers need to consider relative timing between the infection peak day and when the vaccine becomes available.  相似文献   

7.
目的描述在贵阳地区发现的确诊新型冠状病毒感染肺炎(COVID-19)患者的流行病学和临床特点。 方法采用回顾性病例分组研究分析2020年1月29日至2月17日贵州省人民医院隔离病房收治的18例COVID-19确诊患者为研究对象进行回顾性病例分析,其中男性9例,女性9例;年龄15 ~ 68岁,平均(43±16.4)岁。收集患者的一般资料和临床资料,分析其流行病学特点、一般情况、临床症状、实验室检查(血常规、血生化以及相关炎性指标)及CT影像学改变特点等;分析轻症与重症患者血清炎性指标之间的差别及与疾病临床分型的关系。 结果(1)18例患者中,10例(55.6%)为家族聚集性发病;外省(非贵州省)返回人员8例(44.4%),其中湖北返黔人员7例(87.5%),台湾返黔人员1例(12.5%)。(2)患者的主要症状为发热[15例(83.3%)]、呼吸道症状{咳嗽、咳痰[15例(83.3%)],胸闷、呼吸困难[3例(16.7%)]},部分患者伴有腹泻[5例(27.8%)]及其他症状。(3)实验室检查结果以外周血白细胞计数、中性粒细胞计数正常或降低及淋巴细胞计数降低为主要特征,血沉[15例(83%)]、降钙素原(PCT)[10例(56%)]多高于正常范围,部分患者白细胞介素-6(IL-6)可高于正常[7例(39%)]。但多数患者的肝功能、肾功能、心肌酶、C反应蛋白(CRP)的水平未表现出明显异常。与轻症组患者的血清炎症指标相比,重症组患者血清IL-6水平升高[18.34(22.87)pg/mL比1.92(4.37)pg/mL],差异有统计学意义(P<0.05),但CRP、PCT、铁蛋白、乳酸脱氢酶(LDH)、血沉的差异无统计学意义。(4)COVID-19患者大部分有典型的部病变表现,影像学改变特点为病变呈现多发散在斑片状、片状磨玻璃密度影,边缘模糊,部分病变表现为间质性改变,以肺外带为主。 结论贵阳地区COVID-19确诊患者基本都有  相似文献   

8.
《Vaccine》2022,40(4):650-655
BackgroundThe SARS-CoV-2 pandemic was responsible for the death of millions of people around the world, which accelerated the study of vaccines. The BNT162b2 mRNA COVID-19 is a messenger RNA vaccine that encodes the spike protein of the virus. However, the duration of the protection conferred by this vaccine and factors associated with immune responses require validation in large cohorts.MethodsHere, we present data of humoral immune response to vaccination in 4264 healthcare workers, tested before (T0) and 15 and 90 days (T1 and T2, respectively) following vaccination. Peripheral blood was collected for immunological analysis using the Quant SARS-CoV-2 IgG II Chemiluminescent Microparticle Immunoassay (CMIA) to determine anti-spike IgG, receptor binding domain (RBD), S1 subunit of SARS-CoV-2.FindingsAt T0, 96·8% (n = 4129) of participants had IgG antibodies non-reactive to anti-SARS-CoV-2. Fifteen days after completing the vaccination, the IgG overall median titer was significantly elevated (21·7x103 AU/mL). Both for uni- and multivariate logistic regression analyses women presented higher antibody levels than men, independent of age. Titers were significantly altered among age groups, decreasing by each increase in 10-year of age. At 3 months after completing the vaccination, anti-SARS-CoV-2 IgG titers were 6·3-fold diminished.This real-world post-vaccination data confirmed production of a frequent and elevated anti-SARS-CoV-2 IgG titers, associated with high protection rates. Females and younger participants had higher titer 15 days after vaccination, and despite the significant reduction from 15-to-90 days, those with higher pre-vaccination titers maintained higher levels throughout the remaining timepoints.InterpretationThese findings support the need to track humoral immunity kinetics to uncover viral susceptibility and eventually implement re-vaccination, particularly in groups prone to lower humoral immune response.FundingNo external funding was received to conduct this study.  相似文献   

9.
《Vaccine》2021,39(40):5769-5779
SARS-CoV-2 is the etiological agent of COVID19. There are currently several licensed vaccines approved for human use and most of them target the spike protein in the virion envelope to induce protective immunity. Recently, variants that spread more quickly have emerged. There is evidence that some of these variants are less sensitive to neutralization in vitro, but it is not clear whether they can evade vaccine induced protection. In this study, we tested SARS-CoV-2 spike RBD as a vaccine antigen and explored the effect of formulation with Alum/MPLA or AddaS03 adjuvants. Our results show that RBD induces high titers of neutralizing antibodies and activates strong cellular immune responses. There is also significant cross-neutralization of variants B.1.1.7 and B.1.351 and to a lesser extent, SARS-CoV-1. These results indicate that recombinant RBD can be a viable candidate as a stand-alone vaccine or as a booster shot to diversify our strategy for COVID19 protection.  相似文献   

10.
《Vaccine》2023,41(28):4114-4120
People with cystic fibrosis (pwCF) were considered to be clinically vulnerable to COVID-19 and were therefore given priority in the vaccination campaign. Vaccines induced a humoral response in these patients that was comparable to the response observed among the general population. However, the role of the cell-mediated immune response in providing long-term protection against SARS-CoV-2 in pwCF has not yet been defined. In this study, humoral (antibody titre) and cell-mediated immune responses (interferon-γ release) to the BNT162b2 vaccine were measured at different time points, from around 6–8 months after the 2nd dose and up to 8 months after the 3rd dose, in 118 CF patients and 26 non-CF subjects. Subjects were sampled between November 2021 and September 2022 and followed-up for breakthrough infection through October 2022. pwCF mounted a cell-mediated response that was similar to that observed in non-CF subjects. Low antibody titres (<1st quartile) were associated with a higher risk of breakthrough infection (HR: 2.39, 95 % CI: 1.17–4.88), while there was no significant association with low INF-γ levels (<0.3 IU/mL) (HR: 1.38, 95 % CI: 0.64–2.99). Further studies are needed in subgroup of pwCF receiving immunosuppressive therapy, such as organ transplant recipients. This data is important for tailoring vaccination strategies for this clinically vulnerable population.  相似文献   

11.
A novel strain of H1N1 influenza A virus (pH1N1) emerged in 2009, causing a worldwide pandemic. Several studies suggest that this virus is antigenically more closely related to human influenza viruses that circulated prior to 1957 than viruses of more recent seasonal influenza varieties. The extent to which individuals who are naïve to the 2009 pH1N1 virus carry cross-reactive CD8+ T cells is not known, but a certain degree of reactivity would be expected since there is substantial conservation among the internal proteins of the virus. In the present study, we examined the production of multiple cytokines in response to virus from CD8+ T cells in healthy adult subjects, between 18 and 50 years of age (born post 1957), who had no evidence of exposure to the 2009 pH1N1 virus, and had blood collected prior to the emergence of the pandemic in April of 2009. Human peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with a panel of live viruses, and assayed by intracellular cytokine staining and flow cytometry. Although results were variable, most subjects exhibited cytokine positive CD8+ T cells in response to pH1N1. Cytokine producing cells were predominantly single positive (IL2, IFNγ, or TNFα); triple-cytokine producing cells were relatively rare. This result suggests that although many adults carry cross-reactive T cells against the emergent pandemic virus, these cells are in a functionally limited state, possibly because these subjects have not had recent exposure to either seasonal or pandemic influenza strains.  相似文献   

12.
To investigate the effects of chromates on the human immune system, we measured total T lymphocytes and their two major subpopulations (CD4 + and CD8 + T lymphocytes) in the peripheral blood of 19 retired male workers who had been exposed to chromate at a chemical plant. The results indicated that both CD4 + and CD8 + T lymphocytes were significantly decreased, resulting in decreases in total T lymphocytes and total lymphocytes.  相似文献   

13.
目的:分析全国报告的输入性新型冠状病毒(新冠病毒)感染者核酸首次阳性的时间分布特征,为进一步完善入境人员的新型冠状病毒肺炎疫情防控措施提供参考依据。方法:收集2020年7月24日至2021年7月23日各省报告的输入性新冠病毒感染者资料,对入境后核酸首次阳性的时间分布特征进行分析。结果:2020年7月24日至2021年7...  相似文献   

14.
《Vaccine》2022,40(37):5445-5451
Mass vaccination against the disease caused by the novel coronavirus (COVID-19) was a crucial step in slowing the spread of SARS-CoV-2 in 2021. Even in the face of new variants, it still remains extremely important for reducing hospitalizations and COVID-19 deaths. In order to better understand the short- and long-term dynamics of humoral immune response, we present a longitudinal analysis of post-vaccination IgG levels in a cohort of 166 Romanian healthcare workers vaccinated with BNT162b2 with weekly follow-up until 35 days past the first dose and monthly follow-up up to 6 months post-vaccination. A subset of the patients continued with follow-up after 6 months and either received a booster dose or got infected during the Delta wave in Romania. Tests were carried out on 1694 samples using a CE-marked IgG ELISA assay developed in-house, containing S1 and N antigens of the wild type virus.Participants infected with SARS-CoV-2 before vaccination mount a quick immune response, reaching peak IgG levels two weeks after the first dose, while IgG levels of previously uninfected participants mount gradually, increasing abruptly after the second dose. Overall higher IgG levels are maintained for the previously infected group throughout the six month primary observation period (e.g. 36–65 days after the first dose, the median value in the previously infected group is 5.29 AU/ml, versus 3.58 AU/ml in the infection naïve group, p less than 0.001). The decrease of IgG levels is gradual, with lower median values in the infection naïve cohort even 7–8 months after vaccination, compared to the previously infected cohort (0.7 AU/ml versus 1.29 AU/ml, p = 0.006). Administration of a booster dose yielded higher median IgG antibody levels than post second dose in the infection naïve group and comparable levels in the previously infected group.  相似文献   

15.
Vitamins C and D have well-known immune supportive roles, with deficiencies in both vitamins predisposing to increased risk and severity of respiratory infections. Numerous studies have indicated that administration of these vitamins, particularly to people who are deficient, can decrease the risk and severity of respiratory infections. This has stimulated an interest in the potential efficacy of these vitamins in people with novel coronavirus (SARS-CoV-2) infection and its more severe disease (COVID-19). In this overview, we highlight the current research evidence around the multiple levels of immune support provided by vitamins C and D in the context of general respiratory infections and with a focus on the current SARS-CoV-2 pandemic. These include: prevention of infection; attenuating infection symptoms and severity; adjunctive therapy for severe disease; attenuating ongoing sequelae (long COVID); and immunisation support. Although some of these topics have not yet been investigated in great depth concerning SARS-CoV-2 and COVID-19, extensive research into the role of these vitamins in general respiratory infections has highlighted directions for future research in the current pandemic.  相似文献   

16.
《Vaccine》2023,41(35):5072-5078
The continuing high global incidence of COVID-19 and the undervaccinated status of billions of persons strongly motivate the development of a new generation of efficacious vaccines. We have developed an adjuvanted vaccine candidate, PHH-1V, based on a protein comprising the receptor binding domain (RBD) of the Beta variant of SARS-CoV-2 fused in tandem with the equivalent domain of the Alpha variant, with its immunogenicity, safety and efficacy previously demonstrated in mouse models. In the present study, we immunized pigs with different doses of PHH-1V in a prime-and-boost scheme showing PHH-1V to exhibit an excellent safety profile in pigs and to produce a solid RBD-specific humoral response with neutralising antibodies to 7 distinct SARS-CoV-2 variants of concern, with the induction of a significant IFNγ+ T-cell response. We conclude that PHH-1V is safe and elicits a robust immune response to SARS-CoV-2 in pigs, a large animal preclinical model.  相似文献   

17.
Background:The Covid-19 pandemic in Italy has been characterized by three waves of infection during 2020. Vaccination of healthcare workers started in January 2021, earlier than that of other population groups. The main aim of this study is to compare the spread of the pandemic between HCW and the general population focusing on potential effects of the vaccination.Methods:The study consisted of a retrospective analysis of results of RT-PCR tests performed between 6 March 2020 and 4 April 2021 among HCWs from Bologna, Italy, and those of the general population of Emilia Romagna region. We calculated the crude proportion of positive RT-PCR tests over total tests and the crude prevalence of positive test in population; then, we conducted joinpoint analyses using the Joinpoint Regression Program of the National Cancer Institute.Results:The results of the joinpoint analysis show that both φ and ψ ratio indicators have a similar pattern, with a sharp increase during the early phase of the pandemic, and a strong decrease at the end of the first wave around week 15. In both indicators there are no significant changes in the trend after week 25. Pandemic spread among HCWs appeared earlier than in the general population, but it otherwise appeared to have comparable features. A decline in infection was apparent among HCWs after vaccination.Conclusions:Surveillance of HCWs would inform on the epidemic in the general population. The apparent effectiveness of the anti-SarsCoV2 vaccine will likely occur in the general population.  相似文献   

18.
《Vaccine》2022,40(48):6963-6970
BackgroundThe pandemic coronavirus disease 2019 (COVID-19) is a major global public health concern and several protective vaccines, or preventive/therapeutic approaches have been developed. Sinovac-CoronaVac, an inactivated whole virus vaccine, can protect against severe COVID-19 disease and hospitalization, but less is known whether it elicits long-term T cell responses and provides prolonged protection.MethodsThis is a longitudinal surveillance study of SARS-CoV-2 receptor binding domain (RBD)-specific IgG levels, neutralizing antibody levels (NAb), T cell subsets and activation, and memory B cells of 335 participants who received two doses of CoronaVac. SARS-CoV-2 RBD-specific IgG levels were measured by enzyme-linked immunosorbent assay (ELISA), while NAb were measured against two strains of SARS-CoV-2, the Wuhan and Delta variants. Activated T cells and subsets were identified by flow cytometry. Memory B and T cells were evaluated by enzyme-linked immune absorbent spot (ELISpot).FindingsTwo doses of CoronaVac elicited serum anti-RBD antibody response, elevated B cells with NAb capacity and CD4+ T cell-, but not CD8+ T cell-responses. Among the CD4+ T cells, CoronaVac activated mainly Th2 (CD4+ T) cells. Serum antibody levels significantly declined three months after the second dose.InterpretationCoronaVac mainly activated B cells but T cells, especially Th1 cells, were poorly activated. Activated T cells were mainly Th2 biased, demonstrating development of effector B cells but not long-lasting memory plasma cells. Taken together, these results suggest that protection with CoronaVac is short-lived and that a third booster dose of vaccine may improve protection.  相似文献   

19.
PurposeEvaluate the associations of obesity and diabetes with the risk of mortality in critically ill patients infected with SARS-CoV-2.Materials and methodsThis cohort study included 115 adult patients admitted to the ICU with SARS-CoV-2 pneumonia. Anthropometric variables and biochemical (C-reactive protein, ferritin, leukocyte, neutrophils, and fibrinogen) were measured. Multivariate logistic regression analyses were used to investigate the associations.ResultsMean age was 50.6 ± 11.2 years, 68.7% were male. Median BMI was 30.9 kg/m2. All patients had invasive mechanical ventilation. Patients with diabetes had increased risk of mortality with OR of 2.86 (CI 95% 1.1–7.4, p = 0.026); among those patients who, in addition to diabetes had obesity, the risk was de 3.17 (CI 95% 1.9–10.2, p = 0.038). Patients with obesity had 1.25 times greater risk of developing a severe SARS-CoV-2 infection (95% CI 1.09–1.46, p = 0.025). Negative correlation was observed between BMI and the PaO2/FiO2 ratio (r = ?0.023, p < 0.05). Obese patients required more days of mechanical ventilation and longer hospital stay compared to non-obese patients.ConclusionsDiabetes and obesity are risk factors for increasing severity of SARS-CoV-2 infection, and they are both associated with an increase in mortality.  相似文献   

20.
Antibody response against nucleocapsid and spike proteins of SARS-CoV-2 in 11 persons with mild or asymptomatic infection rapidly increased after infection. At weeks 18–30 after diagnosis, all remained seropositive but spike protein–targeting antibody titers declined. These data may be useful for vaccine development.  相似文献   

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