scholarly journals 2709. Immune Response After Diphtheria and Tetanus Toxoid Booster in Patients with Adult-Onset Immunodeficiency with Anti-interferon-γ Autoantibody

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S952-S953
Author(s):  
Dissaruj Tovikkai ◽  
Jakapat Vanichanan ◽  
Kamonwan Jutivorakool

Abstract Background Immunization were the key of prevention in tetanus and diphtherial disease. Nevertheless, in previous observational study, low seroprotection rate of both diphtheria and tetanus were observed in Thai healthy population. Reduced-dose diphtheria and tetanus toxoid vaccine (dT) was recommended to all adult patients regardless of immunologic status. However, data on vaccine efficacy in interferon gamma (IFN-γ) autoantibody were limited. We therefore conducted clinical study to evaluate efficacy and safety of one dose of dT in IFN-γ autoantibody patient compared with healthy individuals at 4 weeks after vaccination. Methods Study was conducted from February to April 2019. Total 18 patients with confirmed IFN-γ autoantibody were enrolled. Baseline tetanus and diphtheria serologic study and 4 weeks after vaccination were examined. Antibody levels were measured with a solid-phase IgG-specific ELISAs (EUROIMMUN, Germany). Geometric mean titers (GMTs) were calculated using the log transformation of serological titers and from taking the antilog mean of the transformed values. Results Seroprevalence of tetanus was 94.5% in healthy population compared with 60.1% in IFN-γ autoantibody patients. While, seroprevalence of diphtheria was 27.8% and 77.8%, respectively. After vaccination, all healthy adults had reached seroprotection level in both diphtheria and tetanus. For patients with IFN-γ autoantibody, 88.9% and 94.4% had anti-tetanus toxin IgG and anti-diphtheria toxin IgG level above 0.1 IU/mL, respectively. These results indicated seroconversion rate of 71% for tetanus and 75% for diphtheria after dT vaccination. (Table 2). In the subgroup analysis, unboosted IFN-γ autoantibody patient had lower tetanus seroconversion rate compared with previously boosted patient (50% vs 100%). Active infection was also associated with lower immune response after tetanus vaccination. There was no severe adverse event in both group. Conclusion This is the first study on immune response after dT vaccination in IFN-γ autoantibody patient. Seroconversion rate of dT vaccine in IFN-γ autoantibody patient were slightly lower than healthy adults. Active infection and previously unboosted patient provided lower immune response of tetanus. Disclosures All authors: No reported disclosures.

2018 ◽  
Vol 146 (16) ◽  
pp. 2079-2085 ◽  
Author(s):  
M. Petráš ◽  
V. Oleár

AbstractAn evaluation of the relationship between predictors and immune response was conducted using data obtained from a clinical trial in 200 Czech healthy adults aged 24–65 years receiving a booster dose of a monovalent tetanus vaccine in 2017. The response was determined from ELISA antibody concentrations of paired sera obtained before and 4 weeks after the immunisation. While all subjects with initial antibody levels <1.2 IU/ml achieved a 100% seroconversion rate (at least a fourfold rise in antibodies), only 8% seroconversion was documented in subjects with initial levels >2.2 IU/ml. The immune response was not affected by sex, age, tetanus vaccine type, concomitant medication, related adverse events or post-vaccination period since there were no significant differences in geometric mean concentrations or seroconversion rates. The seroconversion rate of 56% in smokers was significantly lower than that of 73% achieved in non-smokers. Although the seroconversion rates did not differ between individuals with normal or higher body weight, the adjusted odds ratio (1.3; 95% Cl 1.08–1.60) revealed a positive correlation between seroconversion rate and body mass index (BMI). Although the vaccine-induced response was influenced by pre-vaccination antibody levels, smoking or BMI, the booster immunisation against tetanus produced a sufficient response regardless the predictors.


2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Xuan Zhang ◽  
Juan Wang ◽  
Xi Chen ◽  
Menglu Yu ◽  
Shuangbin Yu ◽  
...  

World Health Organization recommends hepatitis B virus (HBV) immunization at 0, 1, and 6 months. However, studies have suggested that shortening the interval between the first and last HBV immunization can improve completion rates. Less clear is whether accelerated immunization is as immunogenic as standard immunization. Thus, the present study aimed to compare the short-term immunogenicity of yeast-derived hepatitis B vaccine in healthy adults immunized on an accelerated or standard schedule. Between June 2013 and March 2014, individuals from Jinfeng and Longmen, China were randomly assigned to receive the vaccine on an accelerated schedule (at 0, 1, and 2 months; n=201) or a standard schedule (at 0, 1, and 6 months; n=206). Subjects filled out a questionnaire asking about demographic and other health data, and they underwent physical examination. Blood was assayed for HBV surface antigen and HBV surface antibody (HBsAb) at 1–2 months after the three-dose schedule. Multivariate binary logistic regression was used to determine whether the rate of anti-HBs seroconversion differed with immunization schedule. Covariance analysis was used to compare geometric mean HBsAb concentration between the two schedules. The anti-HBs seroconversion rate was 84.6% in the accelerated group and 90.3% in the standard group. After controlling for several potential confounders, the accelerated schedule was associated with significantly lower anti-HBs seroconversion rate (OR: 0.560, 95% CI: 0.318–0.988). Similarly, the accelerated schedule was associated with significantly lower geometric mean HBsAb concentration. These results suggest that the standard schedule is more likely to lead to anti-HBs seroconversion and higher HBsAb levels in adults.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1743-1743
Author(s):  
Yiqing Xu ◽  
Nanda K Methuku ◽  
Praveena Coimbatore ◽  
Theresa Fitzgerald ◽  
Yiwu Huang ◽  
...  

Abstract Abstract 1743 Introduction: Effective vaccinations against 2009 H1N1 have been reported in healthy individuals; however, the response of immunocompromised patients, particularly patients who have hematologic malignancies and who also may be taking cytotoxic myelosuppressive and immunosuppressive treatments, is unclear and is generally considered to be decreased. Methods: We conducted a prospective study to test the immunogenicity of H1N1 vaccination in patients with hematologic malignancies. We enrolled 22 patients, all of them received inactivated monovalent H1N1 2009 vaccine made by Sanofi. Antibody responses were measured by hemaglutination inhibition assay (HAI) at 4–6 weeks and 6–16 weeks. Results: Among the 22 patients, there were 15 males, 7 females, median age 61.5y (range 35–86y). Sixteen patients had active disease, with MGUS+MM (n=4), CLL+NHL (n=5), MDS+AML (n=4) and MPD (n=3), while the other 6 patients were in remission (within 3 years of initial diagnosis), including MM (n=1), CLL+NHL+HD (n=3), AML (n=1) and MPD (n=1). Eleven patients were receiving treatment (within 28 days before or after vaccination) with drugs that have myelosuppressive potential (91%), and 54.5% of the patients were also receiving drugs that have immunosuppressive potential. The median interval of treatment prior to vaccination was 6 days (range 0–84 d) and the median interval of treatment after vaccination was 14 days (0-28 d). At baseline, 23.0% (95% confidence interval [CI], 4–42%) patients had antibody titer ≥ 1:40, and the geometric mean titer was 18.2 (95%CI, 8.6–38.7); at 4–6 weeks, the geometric mean titer was 197.0 (95%CI, 86.5–448.4), and the geometric mean ratio was 12.1 (95%CI 5.28–27.9). The seroconversion rate (4 fold increase in the antibody titer and ≥1:40) was 75% (95%CI, 54–96%), and the post-vaccination seroprotection rate (titer ≥1:40) was 90% (95%CI, 77–100%). When re-tested at 6–16 weeks, the results were not significantly different. Among the 5 patients (25%) who did not show seroconversion, 2 had very high baseline protection titers, 2 did not attain seroprotective titers after vaccination, another one did not show protective titer at 6 weeks, but mounted a titer of 1:40 at 10 weeks. No serious adverse events or hospital admissions from H1N1 infection were documented at 6 months of follow up. Subgroup analyses were performed to evaluate the influence on seroconversion rates of potential factors including (1) the presence or absence of active disease, (2) lymphoproliferative disorders versus myeloid disorders, (3) myelosuppressive drugs, (4) immunosuppressive drugs, and none showed a significant difference. Three patients were treated with Rituximab based chemotherapy, 1 patient who had R-CHOP for NHL showed robust response at 4–6 weeks, while 1 patient who had CLL treated with FCR, and another one with NHL treated with R-Bendamustine failed to develop response. These are the only 2 patients who did not show seroconversion or seroprotective titers in this study. Conclusion: Patients with hematologic malignancies are able to generate an immune response to the H1N1 vaccine. The lower boundaries of CI of seroconversion rate (54%) and that of seroprotection rate (77%) are above what are recommended by the US FDA for an effective vaccine. Among the patients who developed an immune response, all but one demonstrated response within 4–6 weeks. Patients receiving Rituximab based treatment nevertheless can generate an effective immune response. Disclosures: No relevant conflicts of interest to declare.


2012 ◽  
Vol 23 (7) ◽  
pp. 464-467 ◽  
Author(s):  
S Kourkounti ◽  
N Mavrianou ◽  
Va Paparizos ◽  
K Kyriakis ◽  
M Hatzivassiliou ◽  
...  

HIV-infected patients are at increased risk for acquiring hepatitis A virus (HAV) infection. We evaluated the seroconversion rate (anti-HAV antibodies ≥ 20 mIU/ml) and the geometric mean antibody titres (GMTs) in a group of 351 HIV infected men, who had received two doses of a hepatitis A vaccine. We analysed blood samples collected at one, six, 12 and 18 months following the administration of the second dose of the vaccine. The seroconversion rate one month after the second dose of the vaccine was 74.4% (260/351). At month 18 after the end of vaccination, 56.1 % of the subjects remained seropositive. GMTs were 315, 203,153 and 126 mIU/ml at months 1,6, 12, and 18, respectively. Logistic regression revealed that the CD4 count is the only factor affecting response to vaccination ( P = 0.019). A higher response rate and higher GMTs were observed in patients with CD4 counts ≥500 cells/mm3 (76.6%) than in patients with CD4 counts 200–499 cells/mm3. In conclusion, even in patients with near-normal CD4 counts, the response to the hepatitis A vaccine is impaired.


2022 ◽  
Author(s):  
Shi Zou ◽  
Mengmeng Wu ◽  
Fangzhao Ming ◽  
Songjie Wu ◽  
Wei Guo ◽  
...  

Abstract Background: Multi-types COVID-19 vaccines have shown safety and efficacy against COVID-19 in adults. Although current guidelines encourage people living with HIV(PLWH) to take COVID-19 vaccines, whether their immune response to COVID-19 vaccines is distinct from HIV-free individuals is still unclear. Methods: Between March to June 2021, 48 PLWH and 40 HNC, aged 18 to 59 years, were enrolled in the study in Wuchang district of Wuhan city. All of them received inactivated COVID-19 vaccine at day 0 and the second dose at day 28. The primary safety outcome was the combined adverse reactions within 7days after each injection. The primary immunogenicity outcomes were neutralizing antibodies (nAbs) responses by chemiluminescence and total specific IgM and IgG antibodies responses by ELISA and colloidal gold at baseline (day 0), day 14, day 28, day 42, and day 70.Results: In total, the study included 46 PLWH and 38 HNC who finished 70 days’ follow-up. The frequency of adverse reactions to the first and second dose was not different between PLWH (30% and 11%) vs HNC (32% and 24%). There were no serious adverse events. NAbs responses among PLWH peaked at day 70, while among HNC peaked at day 42. At day 42, the geometric mean concentration (GMC) and seroconversion rate of nAbs among PLWH were 4.46 binding antibody units (BAU)/mL (95% CI, 3.18-5.87) and 26% (95% CI, 14-41), which were lower than that among HNC [GMC (18.28 BAU/mL, 95% CI, 10.33-32.33), seroconversion rate (63%, 95% CI, 44-79)]. IgG responses among both PLWH and HNC peaked at day 70. At day 70, the geometric mean ELISA units (GMEU) and seroconversion rate of IgG among PLWH were 0.193 ELISA units (EU)/mL (95% CI, 0.119-0.313) and 51% (95% CI, 34-69), which was lower than that among HNC [GMEU (0.379 BAU/mL, 95% CI, 0.224-0.653), seroconversion rate (86%, 95% CI, 64-97)]. Conclusion: Early humoral immune response to the inactivated COVID-19 vaccine was weaker and delayed among the PLWH population than that among HNC. This observation remained consistent regardless of a high CD4 count and a low HIV viral load suppressed by antiretroviral therapy (ART).


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 868
Author(s):  
Fabiana Albani Zambuzi ◽  
Priscilla Mariane Cardoso-Silva ◽  
Ricardo Cardoso Castro ◽  
Caroline Fontanari ◽  
Flavio da Silva Emery ◽  
...  

Decitabine is an approved hypomethylating agent used for treating hematological malignancies. Although decitabine targets altered cells, epidrugs can trigger immunomodulatory effects, reinforcing the hypothesis of immunoregulation in treated patients. We therefore aimed to evaluate the impact of decitabine treatment on the phenotype and functions of monocytes and macrophages, which are pivotal cells of the innate immunity system. In vitro decitabine administration increased bacterial phagocytosis and IL-8 release, but impaired microbicidal activity of monocytes. In addition, during monocyte-to-macrophage differentiation, treatment promoted the M2-like profile, with increased expression of CD206 and ALOX15. Macrophages also demonstrated reduced infection control when exposed to Mycobacterium tuberculosis in vitro. However, cytokine production remained unchanged, indicating an atypical M2 macrophage. Furthermore, when macrophages were cocultured with lymphocytes, decitabine induced a reduction in the release of inflammatory cytokines such as IL-1β, TNF-α, and IFN-γ, maintaining IL-10 production, suggesting that decitabine could potentialize M2 polarization and might be considered as a therapeutic against the exacerbated immune response.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ernesta Cavalcanti ◽  
Maria Antonietta Isgrò ◽  
Domenica Rea ◽  
Lucia Di Capua ◽  
Giusy Trillò ◽  
...  

Abstract Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of people globally, requiring the development of billions of different vaccine doses. The SARS-CoV-2 spike mRNA vaccine (named BNT162b2/Pfizer), authorized by the FDA, has shown high efficacy in preventing SARS-CoV-2 infection after administration of two doses in individuals 16 years of age and older. In the present study, we retrospectively evaluated the differences in the SARS-CoV-2 humoral immune response after vaccine administration in the two different cohorts of workers at the INT - IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy): previously infected to SARS-CoV-2 subjects and not infected to SARS-CoV-2 subjects. Methods We determined specific anti-RBD (receptor-binding domain) titers against trimeric spike glycoprotein (S) of SARS-CoV-2 by Roche Elecsys Anti-SARS-CoV-2 S immunoassay in serum samples of 35 healthcare workers with a previous documented history of SARS-CoV-2 infection and 158 healthcare workers without, after 1 and 2 doses of vaccine, respectively. Moreover, geometric mean titers and relative fold changes (FC) were calculated. Results Both previously infected and not infected to SARS-CoV-2 subjects developed significant immune responses to SARS-CoV-2 after the administration of 1 and 2 doses of vaccine, respectively. Anti-S antibody responses to the first dose of vaccine were significantly higher in previously SARS-CoV-2-infected subjects in comparison to titers of not infected subjects after the first as well as the second dose of vaccine. Fold changes for subjects previously infected to SARS-CoV-2 was very modest, given the high basal antibody titer, as well as the upper limit of 2500.0 BAU/mL imposed by the Roche methods. Conversely, for naïve subjects, mean fold change following the first dose was low ($$ \overline{x} $$ x ¯ =1.6), reaching 3.8 FC in 72 subjects (45.6%) following the second dose. Conclusions The results showed that, as early as the first dose, SARS-CoV-2-infected individuals developed a remarkable and statistically significant immune response in comparison to those who did not contract the virus previously, suggesting the possibility of administering only one dose in previously SARS-CoV-2-infected subjects. FC for previously infected subjects should not be taken into account for the generally high pre-vaccination values. Conversely, FC for not infected subjects, after the second dose, were = 3.8 in > 45.0% of vaccinees, and ≤ 3.1 in 19.0%, the latter showing a potential susceptibility to further SARS-CoV-2 infection.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mary Jo Rademacher ◽  
Anahi Cruz ◽  
Mary Faber ◽  
Robyn A. A. Oldham ◽  
Dandan Wang ◽  
...  

AbstractInterleukin-12 (IL-12) is an inflammatory cytokine that has demonstrated efficacy for cancer immunotherapy, but systemic administration has detrimental toxicities. Lentiviral transduction eliciting IL-12-producing human sarcoma for autologous reintroduction provides localized delivery for both innate and adaptive immune response augmentation. Sarcoma cell lines and primary human sarcoma samples were transduced with recombinant lentivirus engineering expression of human IL-12 (hu-IL-12). IL-12 expressing sarcomas were assessed in vitro and in vivo following implantation into humanized NSG and transgenic human IL-15 expressing (NSG.Tg(Hu-IL-15)) murine models. Lentiviral transduction (LV/hu-IL-12) of human osteosarcoma, Ewing sarcoma and rhabdomyosarcoma cell lines, as well as low-passage primary human sarcomas, engendered high-level expression of hu-IL-12. Hu-IL-12 demonstrated functional viability, eliciting specific NK cell-mediated interferon-γ (IFN-γ) release and cytotoxic growth restriction of spheroids in vitro. In orthotopic xenograft murine models, the LV/hu-IL-12 transduced human sarcoma produced detectable IL-12 and elicited an IFN-γ inflammatory immune response specific to mature human NK reconstitution in the NSG.Tg(Hu-IL-15) model while restricting tumor growth. We conclude that LV/hu-IL-12 transduction of sarcoma elicits a specific immune reaction and the humanized NSG.Tg(Hu-IL-15) xenograft, with mature human NK cells, can define in vivo anti-tumor effects and systemic toxicities. IL-12 immunomodulation through autologous tumor transduction and reintroduction merits exploration for sarcoma treatment.


2021 ◽  
Vol 9 (6) ◽  
pp. e002269
Author(s):  
Shota Aoyama ◽  
Ryosuke Nakagawa ◽  
Satoshi Nemoto ◽  
Patricio Perez-Villarroel ◽  
James J Mulé ◽  
...  

BackgroundThe temporal response to checkpoint blockade (CB) is incompletely understood. Here, we profiled the tumor infiltrating lymphocyte (TIL) landscape in response to combination checkpoint blockade at two distinct timepoints of solid tumor growth.MethodsC57BL/6 mice bearing subcutaneous MC38 tumors were treated with anti-PD-1 and/or anti-CTLA-4 antibodies. At 11 or 21 days, TIL phenotype and effector function were analyzed in excised tumor digests using high parameter flow cytometry. The contributions of major TIL populations toward overall response were then assessed using ex vivo cytotoxicity and in vivo tumor growth assays.ResultsThe distribution and effector function among 37 distinct TIL populations shifted dramatically between early and late MC38 growth. At 11 days, the immune response was dominated by Tumor necrosis factor alpha (TNFα)-producing NKT, representing over half of all TIL. These were accompanied by modest frequencies of natural killer (NK), CD4+, or CD8+ T cells, producing low levels of IFN-γ. At 21 days, NKT populations were reduced to a combined 20% of TIL, giving way to increased NK, CD4+, and CD8+ T cells, with increased IFN-γ production. Treatment with CB accelerated this switch. At day 11, CB reduced NKT to less than 20% of all TIL, downregulated TNFα across NKT and CD4+ T cell populations, increased CD4+ and CD8+ TIL frequencies, and significantly upregulated IFN-γ production. Degranulation was largely associated with NK and NKT TIL. Blockade of H-2kb and/or CD1d during ex vivo cytotoxicity assays revealed NKT has limited direct cytotoxicity against parent MC38. However, forced CD1d overexpression in MC38 cells significantly diminished tumor growth, suggesting NKT TIL exerts indirect control over MC38 growth.ConclusionsDespite an indirect benefit of early NKT activity, CB accelerates a switch from TNFα, NKT-driven immune response toward an IFN-γ driven CD4+/CD8+ T cell response in MC38 tumors. These results uncover a novel NKT/T cell switch that may be a key feature of CB response in CD1d+ tumors.


Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 492
Author(s):  
Yunhwa Kim ◽  
Ji-Young Hwang ◽  
Kyung-Min Lee ◽  
Eunsil Lee ◽  
Hosun Park

The prevalence of varicella is especially high among children in the age group of 4–6 years in South Korea, regardless of vaccination. We investigated the immune status of healthy children enrolled in day-care centers and compared pre- and post-vaccination immunity. Antibody titers were measured using a glycoprotein enzyme-linked immunosorbent assay (gpEIA) kit, and the seroconversion rate was assessed using a fluorescent antibody to membrane antigen (FAMA) test. Among 541 vaccinated children, 109 (20.1%) had breakthrough varicella. However, 13 (72.2%) of the 18 unvaccinated children had a history of varicella. The gpEIA geometric mean titers (GMTs) of pre- and 5 weeks post-vaccination in 1-year-old children were 14.7 and 72 mIU/mL, respectively, and the FAMA seroconversion rate was 91.1%. The gpEIA GMTs of 2-, 3-, 4-, 5-, and 6-year-old children were 104.1, 133.8, 223.5, 364.1, and 353.0 mIU/mL, respectively. Even though the gpEIA GMT increased with age, the pattern of gpEIA titer distribution in 4- to 6-year-old vaccinees without varicella history represented both waning immunity and natural boosting immunity. These results suggest that some vaccinees are vulnerable to varicella infection. Therefore, it is necessary to consider a two-dose varicella vaccine regimen in South Korea.


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