scholarly journals Characterization of the Humoral and Cellular Immune Response Against the Natural Infection By Sars-Cov-2 in Oncohematological Patients with Post-COVID19 Autologous Transplantation

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 5040-5040
Author(s):  
Adrián Sánchez-Tornero ◽  
Lorena Vigon ◽  
Guiomar Casado-Fernandez ◽  
Javier Garcia-Pérez ◽  
Elena Mateos ◽  
...  

Abstract Background : Oncohematological patients may have a lower immune response against SARS-CoV-2, both to natural infection and to vaccines. Most studies have focused on the analysis of the humoral response, which means that the information available on the cellular response against SARS-CoV-2 in these patients is limited. Current recommendations include vaccination against SARS-CoV-2 in patients undergoing autologous hematopoietic stem cell transplantation (AHSTC), regardless of whether they have been previously exposed to the virus. These recommendations are based on previous studies with other vaccines. Therefore, it is necessary to analyze the immune response that is developed in these patients in order to make specific recommendations for COVID-19 vaccination. Objective : To study the humoral and cellular immune response before and after AHSTC in patients with oncohematological neoplasms who were exposed to SARS-CoV-2 before the transplantation. Materials & methods : Nine patients with previous exposure to SARS-CoV-2 who underwent AHSTC (Table 1) and 8 healthy donors who recovered from mild COVID-19 were recruited from Hospital Ramón y Cajal and Primary Healthcare Center Pedro Laín Entralgo (Madrid, Spain), respectively. Specific direct cellular cytotoxicity (DCC) of PBMCs from these patients against Vero E6 cells infected with pseudotyped SARS-CoV-2 was determined. The activation of caspase-3 in Vero cells was measured after 1 hour of co-culture with PBMCs, in which cytotoxic cell populations were analyzed by flow cytometry. Antibody-dependent cellular cytotoxicity (ADCC) was analyzed by quantifying the binding of Annexin V to rituximab-coated Raji cells as targets of PBMCs. Results : 1) 66% of AHSTC patients did not develop detectable levels of IgGs against SARS-CoV-2 (Fig. 1). In 33% of these patients with detectable IgG, the titers decreased after AHSTC, as well as their neutralizing capacity (Fig. 1B and C). 2) AHSTC patients showed increased levels of immature B cells (9.5-fold; p=0.0586) and plasmablasts (28.8-fold), in comparison with healthy donors who had mild COVID-19, while naive and resting memory B cells decreased 1.7- and 6.9-fold, respectively. 3) Specific DCC against SARS-CoV-2-infected cells increased 1.5-fold in comparison with healthy donors (Fig. 2A). Cytotoxic populations with NK phenotypes (CD3-CD56+CD16+), NKT (CD3+CD56+CD16+), and CD8+ T cells (CD3+CD8+TCRγδ+) increased 1.9- (p=0.0311), 1.9- (p=0.0592), and 1.6-fold, respectively (Fig. 2B). ADCC increased 2.1-fold in PBMCs from AHSTC patients in comparison with healthy donors (p = 0.0592). Conclusions : Our data show for the first time how the humoral and cellular immune response against the natural infection by SARS-Cov-2 may be modified in patients who were subsequently subjected to AHSTC. Although the humoral response may be reduced after AHSTC, the specific cellular response showed an increased cytotoxic activity. These results could be extrapolated to patients who were vaccinated against COVID-19 prior to AHSTC. Therefore, this information could be useful to define the recommendations for COVID-19 vaccination after AHSTC. Figure 1 Figure 1. Disclosures Garcia-Gutiérrez: Pfizer: Research Funding; Incyte: Consultancy; Novartis: Consultancy; Bristol-Myers Squibb: Consultancy.

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 195-195
Author(s):  
Magdalena Corona De Lapuerta ◽  
Sara Rodriguez-Mora ◽  
Guiomar Casado-Fernandez ◽  
Javier Garcia-Pérez ◽  
Lorena Vigon ◽  
...  

Abstract Background: Oncohematological patients present a variable immune response against many vaccines, due to the immunodeficiency caused by the disease and its treatment. The experience of vaccination against COVID-19 in oncohematological patients is low and mostly limited to studies of humoral immunity. However, the humoral and cellular immune responses between different oncohematological diseases (OHD) have not been compared. Objective: To compare the humoral and cellular immune responses in four groups of patients with OHD after receiving the first dose of one COVID-19 vaccine. Materials & methods: We recruited 53 patients in four groups according to diagnosis: Chronic Lymphatic Leukemia (CLL) (n=14), Chronic Myeloid Leukemia (CML) (n=11), Multiple Myeloma (MM) (n=15), and Allogeneic Hematopoietic Stem Cell Transplantation (ASCT) (n=13) (Table 1). Samples were collected prior to vaccination and 3 weeks after receiving one dose of COMIRNATY (BioNTech-Pzifer), mRNA-1273 (Moderna), or AZD1222 (AstraZeneca). Twenty-six healthy donors with similar vaccination pattern were recruited. IgG titers against SARS-CoV-2 were quantified by Euroimmun-Anti-SARS-CoV-2 ELISA. Direct cellular cytotoxicity (DCC) was determined against Vero E6 cells infected with pseudotyped SARS-CoV-2, measuring caspase-3 activation after co-culture with PBMCs, in which cytotoxic populations were phenotyped by flow cytometry. Antibody-dependent cellular cytotoxicity (ADCC) analyses were performed using Annexin V on Raji cells as a target. Results: 1) Early humoral response against COVID-19 vaccination in patients with CML was 5.1- (p<0.0001), 2.8- (p=0.0027), and 3.2-fold (p<0.0001) higher than in patients with CLL, MM and HSCT, respectively, and 3.5-fold higher than in healthy donors (p=0.0460) (Fig. 1). 84% of CLL patients did not develop detectable IgG titers. Individuals with OHD developed lower titres of neutralizing antibodies than healthy donors. 2) Unspecific ADCC was overall reduced in patients with OHD, mostly in individuals with ASCT (3.2-fold lower (p<0,0001)), whereas ADCC was reduced 2.2- (p<0.0001), 1.8- (p=0.0040), and 2.2-fold (p<0.0001) in individuals with CLL, CML and MM, respectively (Fig. 2A). However, specific DCC was increased 4.7-, 8.1- (p=0.0189), and 2.1-fold, respectively, in PBMCs from patients with CLL, MM, or ASCT, in comparison with healthy donors, whereas patients with CML showed a very similar response than healthy donors (Fig. 2B). 3) Levels of CD3+CD8+TCRγδ+ T cells were increased 2.2-, 2.1-, 2.7-, and 4.3-fold (p=0.0394) in patients with CLL, CML, MM, and ASCT, respectively, in comparison with healthy donors. CD3+CD8-TCRγδ+ T cells were also increased in patients with OHD, expressing high levels of the degranulation marker CD107a. However, the levels of CD3-CD56+CD107a+ NK cells were reduced 4.2- (p=0.0003) and 3.6-fold (p=0.0010) in PBMCs from patients with MM and ASCT, respectively, in comparison with healthy donors. Conclusions: We found significant differences in the early humoral immune response after one single dose of COVID-19 vaccine depending on the OHD analyzed. It was observed for the first time that the early cytotoxic immune response is efficient in all groups of patients, although superior in those who were not exposed to ASCT. Most cytotoxic activity relied on CD8+ T cells. These data can be useful to determine the efficacy of COVID-19 vaccines in patients with OHD. Figure 1 Figure 1. Disclosures Garcia Gutierrez: BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding.


2021 ◽  
Vol 22 (6) ◽  
pp. 1111-1120
Author(s):  
I. A. Goldina ◽  
E. V. Markova ◽  
I. A. Orlovskaya ◽  
L. B. Toporkova ◽  
V. A. Kozlov

Our aim was to evaluate immunomodulatory properties of an original bioflavonoid complex in experimental immune disturbances induced by cyclophosphamide (Cy). We have studied morphometric indexes of thymus and spleen, as well as blood leukocyte counts, cell proliferative activity in lymphoid organs, delayed hypersensitivity responses to T cell-dependent antigen, along with differentiation activity of bone marrow stem cells in experimental animals during Cy-induced immune suppression after a course of bioflavonoid treatment. Suspension of the bioflafonoid complex was introduced to the male mice (СВАхC57Bl/6)F1 aged 12- 14 weeks at a daily dose of 2 mg/animal (80 mg/kg), per os, using gastric catheter, over 14 days. Cytostatic immunosuppression was produced by a single intraperitoneal Cy injection. Proliferative activity of spleen and thymic cells was determined by standard method with Н3 -thymidine incorporation in the 72-h cell culture. Cellular immune response was assayed by the degree of delayed-type hypersensitivity development in response to sheep erythrocytes. The number of hematopoietic progenitors was evaluated by culturing bone marrow cells in methylcellulose-based medium. The experiments have shown mitigation of immunosuppressive effects induced by Cy, in the course of bioflavonoid complex treatment, with respect to absolute and relative mass of lymphoid organs and leukocyte numbers in peripheral blood. Moreover, we have demonstrated decreased effects of Cy treatment upon the spontaneous activity of spleen cells, mitogen-induced thymocyte and splenocyte proliferation, intensivity of delayed-type hypersensitivity response that reached the values of intact animals. Following the course of bioflavonoids, we have revealed an increase in early hematopoietic progenitors. Alleviation of Cy-induced suppressive effects upon cellular immune response, proliferation rates of immune cells, as well as stimulation of hematopoietic stem cell functions suggest a sufficient capacity of the original bioflavonoid complex for modulation of immunity and hematopoiesis, thus presenting experimental proofs for its potential usage as an adjuvant treatment of the patients with malignant diseases.


2019 ◽  
Vol 87 (12) ◽  
Author(s):  
Pratik P. Vikhe ◽  
Tom Purnell ◽  
Steve D. M. Brown ◽  
Derek W. Hood

ABSTRACT Nontypeable Haemophilus influenzae (NTHi) is a major pathogen causing acute otitis media (AOM). The pathology of AOM increases during long-term infection in the middle ear (ME), but the host cellular immune response to bacterial infection in this inflamed environment is poorly understood. Using the Junbo mouse, a characterized NTHi infection model, we analyzed the cellular response to NTHi infection in the Junbo mouse middle ear fluid (MEF). NTHi infection increased the total cell number and significantly decreased the proportion of live cells in the MEF at day 1, and this further decreased gradually on each day up to day 7. Flow cytometry analysis showed that neutrophils were the dominant immune cell population in the MEF and that NTHi infection significantly increased their proportion whereas it decreased the monocyte, macrophage, and dendritic cell proportions. Neutrophil and macrophage numbers increased in blood and spleen after NTHi infection. The T-cell population was dominated by T-helper (Th) cells in noninoculated MEF, and the effector Th (CD44+) cell population increased at day 2 of NTHi infection with an increase in IL-12p40 levels. Sustained NTHi infection up to 3 days increased the transforming growth factor β levels, decreasing the effector cell population and increasing the T-regulatory (T-reg) cell population. In the preinflamed ME environment of the Junbo mouse, neutrophils are the first responder to NTHi infection followed by T-reg immune suppressive cells. These data indicate that sustained NTHi infection in the ME induces the immune suppressive response by inducing the T-reg cell population and reducing immune cell infiltration, thus promoting longer-term infection.


2017 ◽  
Vol 3 (6) ◽  
pp. 234
Author(s):  
Rahmahani J ◽  
Handijatno D ◽  
Tyaningsih W ◽  
Suwarno Suwarno

The aims of this research is to determine the ability of sub unit lipopolysacharide(LPS) vaccine of Brucella abortus strain S-19 in mice and goat, including IgM and sub classes IgG antibody humoral response, cellular mediated immune response (IL-2, IFN- γ) in mice, also IgG as humoral immunity, IL-4 and IL-12 as cellular immunity, comparison affectivity with Brucella abortus strain RB-51 vaccine in goat . This research has two steps methods. Step first, 30 Balb C mice were divided into 3 groups and vaccinated subcutaneously, First group injectedB. abortus S-19, second group injected LPS and third group injected sodium chloride solution. Booster vaccination was conducted every two weeks till the eight week after first vaccination. The second step performed vaccinated to 30 goats divided into three groups. First group was injected by subcutaneous LPS 50 µg/ml and second group injected LPS 100 µg/ml and the third group injected with sodium chloride as control. Booster vaccination conducted 2 weeks after first vaccination and second vaccination. Result of the research conferred. Result research, antibody response in mice showed vaccination by LPS of B. abortus S-19 showed higher titer than vaccination by whole cells but inverse cellular response. The both vaccines showed induce subclass antibody response, vaccination by LPS tendency to IgM response but vaccination by Whole cells active vaccine tendency to IgG1, IgG 2a and IgG2b. Response antibody in goat on two weeks after first vaccination, vaccination with LPS of B. abortus S-19, dose 50 µg/ml failed or zero titer IgG response but dose 100 µg/ml was 500response antibody on two weeks after second vaccination by dose 50 µg/ml was 340 but by dose 100 µg/ml was 960, while cellular IL-12 response two weeks after first vaccination by dose 50 µg/ml was 22.88 pg/ml but by 100 µg/ml was 62.15 pg/ml. Response cellular IL -12 two weeks after second vaccination 50 µg/ml was 12.04 pg/ml while by dose100 µg/ml was 130.88pg/ml    Cellular immune response IL-4 on two weeks after first vaccination, dose 50 µg/ml showed 55.57 pg/ml but by dose100 µg/ml was 49.35 pg/ ml. Response cellular IL-4 on two weeks after second vaccination by dose 50 µg/ml  was 22.17 pg/ml but by dose 100 µg/ml was 143.89 pg/ml Keyword: Vaccine sub-unit LPS of Brucella abortus S-19, Humoral antibody, Cellular antibody


2021 ◽  
Author(s):  
Yunmei Huang ◽  
Yuting Yang ◽  
Tingting Wu ◽  
Zhiyu Li ◽  
Yao Zhao

Abstract Background: Hepatitis B vaccination is the most cost-effective way to prevent HBV infection. Currently, hepatitis B vaccine (HepB) efficacy was usually assessed by anti-HBs level, but there were little comprehensive analyses of humoral and cellular immune response to HepB in children after neonatal immunization. Methods: A total of 145 children with primary hepatitis B immunization history were involved in this study to evaluate the efficacy of HepB. Blood samples were obtained from 80 eligible children before one dose of HepB booster and 41 children post-booster. Children with anti-HBs at a low level (<10mIU/mL and [10,100) mIU/mL) were received one dose of HepB booster after informed consent. Subjects were be measured anti-HBs, HBsAg-specific T cell responses and frequency of B cell subsets before and after booster. Results: Among 80 subjects, 81.36% of children showed both T cell and anti-HBs responses positive at baseline. After one dose of booster, anti-HBs titer (P<0.0001), positive rate of HBsAg-specific T cell response (P=0.0036) and magnitude of SFCs (P=0.0003) increased significantly. Comparing preexisting anti-HBs titer <10mIU/mL with anti-HBs titer [10,100) mIU/mL, anti-HBs response (P=0.0005) and HBsAg-specific T lymphocyte response (P<0.0001) increased significantly. The change tendency of HBV specific humoral response is complementary to T cellular response with age. Conclusion: Protection from primary HBV immunization persists long on account of the complementary presence of HBV-specific humoral and T-cellular immune response. One dose of HepB booster is efficient enough to produce protective anti-HBs and enhance HBsAg-specific T cell response. In the HBV endemic areas, HepB booster immunization is still the most economical and effective way to prevent HBV infection, especially in children without anti-HBs.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
C. E. Rivas-Santiago ◽  
G. G. Guerrero

The role of type I IFNs in the pathogenesis and control of mycobacterial infection is still controversial. It has been reported that type I IFNs exacerbated M. tuberculosis infection through hampering Th1 type cellular immune response. However, under certain conditions they can act as natural immune adjuvants for commercial vaccines. At this point, we have reported recently that successive IFN-alpha boosting of Mycobacterium bovis Bacillus Calmette Güerin (BCG) vaccinated mice protected adult mice from intradermal M. lepraemurium infection and a difference in iNOS was observed. In the present work, we have found that intramuscular IFN-α boosting of Mycobacterium bovis Bacillus Calmette Güerin (BCG) vaccine, either in vitro (human cell line or macrophages derived from PBMC) or in vivo (aerosol mouse model of MTb infection), promoted mostly the development of specific anti-antimycobacterial Th1 type cytokines (IFN-γ; IL-12, TNF-alpha, and IL-17; IL1β) while bacterial load reduction (0.9 logs versus PBS or BCG vaccine) was observed. These findings indicate that, under the experimental settings reported here, interferon alpha can drive or affect the TH cellular immune response in favour of BCG-inducing immunity against M. tuberculosis infection.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Efthimios Deligeoroglou ◽  
Aikaterini Giannouli ◽  
Nikolaos Athanasopoulos ◽  
Vasileios Karountzos ◽  
Anastasia Vatopoulou ◽  
...  

High prevalence and mortality rates of cervical cancer create an imperative need to clarify the uniqueness of HPV (Human Papillomavirus) infection, which serves as the key causative factor in cervical malignancies. Understanding the immunological details and the microenvironment of the infection can be a useful tool for the development of novel therapeutic interventions. Chronic infection and progression to carcinogenesis are sustained by immortalization potential of HPV, evasion techniques, and alterations in the microenvironment of the lesion. Inside the lesion, Toll-like receptors expression becomes irregular; Langerhans cells fail to present the antigens efficiently, tumor-associated macrophages aggregate resulting in an unsuccessful immune response by the host. HPV products also downregulate the expression of microenvironment components which are necessary for natural-killer cells response and antigen presentation to cytotoxic cells. Additionally HPV promotes T-helper cell 2 (Th2) and T-regulatory cell phenotypes and reduces Th1 phenotype, leading to suppression of cellular immunity and lesion progression to cancer. Humoral response after natural infection is inefficient, and neutralizing antibodies are not adequate in many women. Utilizing this knowledge, new endeavors, such as therapeutic vaccination, aim to stimulate cellular immune response against the virus and alter the milieu of the lesion.


2020 ◽  
Vol 6 (4) ◽  
pp. 347
Author(s):  
Marcelo Valdemir de Araújo ◽  
Samuel Rodrigues Dos Santos Júnior ◽  
Joshua D. Nosanchuk ◽  
Carlos Pelleschi Taborda

The peptide P10 is a vaccine candidate for Paracoccidioidomycosis, a systemic mycosis caused by fungal species of the genus Paracoccidioides spp. We have previously shown that peptide P10 vaccination, in the presence of several different adjuvants, induced a protective cellular immune response mediated by CD4+ Th1 lymphocytes that was associated with the increased production of IFN-γ in mice challenged with a virulent isolate of Paracoccidoides brasiliensis. Cationic liposomes formulated with dioctadecyldimethylammonium and trehalose dibehenate (DDA/TDB, termed also CAF01–cationic adjuvant formulation) have been developed for safe administration in humans and CAF01 liposomes are utilized as an adjuvant for modulating a robust Th1/Th17 cellular response. We evaluated the efficacy of the adsorption of peptide P10 to CAF01 cationic liposomes and used the generated liposomes to vaccinate C57Bl/6 mice infected with P. brasiliensis. Our results showed that P10 was efficiently adsorbed onto CAF01 liposomes. The vaccination of infected mice with cationic liposomes formulated with DDA/TDB 250/50 µg/mL and 20 µg of P10 induced an effective cellular immune response with increased levels of Th17 cytokines, which correlated with significant decreases in the fungal burdens in lungs and protective granulomatous tissue responses. Hence, cationic liposomes of DDA/TDB 250/50 µg/mL with 20 µg of P10 are a promising therapeutic for safely and effectively improving the treatment of paracoccidioidomycosis.


2019 ◽  
Author(s):  
Carolina Argondizo-Correia ◽  
Lourdes Rehder de Andrade Vaz-de-Lima ◽  
Elaine Uchima Uehara ◽  
Eder Gatti Fernandes ◽  
Helena Keico Sato ◽  
...  

AbstractPertussis resurgence worldwide calls for new prevention strategies, as the recently incorporated vaccine booster dose during pregnancy, whose aim is to protect newborns from infection. In Brazil, maternal Tdap vaccination is recommended since 2014, and we reported that this strategy promotes high transplacental transfer of anti-PT IgG and it is effective in protecting infants early in life. Young children are the most susceptible group and with higher mortality rates, however, it is not well known whether the elicited anti-pertussis maternal antibodies could influence in the children’s immune responses further in life, especially after their own vaccination against pertussis. Considering this scenario, we conducted a study with children born to mothers who either received or not the booster dose during pregnancy, after their primary pertussis vaccination, in order to investigate the first impact of maternal immunisation on the response to infant immunisation regarding the cellular immune response, while comparing with data from the literature. As transfer of maternal antibodies could result in attenuation of the immune response to vaccination in infants, this study performed to determine whether higher levels of maternal antibodies could influence in the immune response of infants to the whole-pertussis vaccination series. Results showed no difference in cytokine production between groups, a first suggestion that maternal vaccination may not interfere with recognition and cellular response generation to vaccination. This data, together with humoral immunity and epidemiological studies, is important for the implementation of maternal immunisation strategies nationwide and will contribute to assure public policies regarding vaccination schemes.ImportancePertussis, or whopping cough, is a respiratory infectious disease caused by a bacterial agent, resulting in violent coughs and possibly death in vulnerable groups, such as young children and neonates. It is known that pregnant mothers transfer antibodies to their developing foetuses for protection in early life, however anti-pertussis antibodies are not highly detected in young children. Thus, a pertussis maternal vaccination was implemented to increase maternal anti-pertussis antibodies levels in pregnant women and therefore the transference to the foetus. However, maternal antibodies can also interfere in the child immune response in the first months of life. The significance of our research is in analysing the cellular immune response of children born from pertussis-vaccinated mothers, which will give a first glimpse on how maternal antibodies could modulate the child’s response to pertussis in early life.


Sign in / Sign up

Export Citation Format

Share Document