scholarly journals Gestational pertussis vaccination and the infant’s cellular immune response against whole-cell pertussis vaccine in the first year of life

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.

Vaccine ◽  
2020 ◽  
Vol 38 (1) ◽  
pp. 20-28 ◽  
Author(s):  
Marjolein R.P. Orije ◽  
Kirsten Maertens ◽  
Véronique Corbière ◽  
Nasamon Wanlapakorn ◽  
Pierre Van Damme ◽  
...  

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.


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.


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.


2020 ◽  
Author(s):  
Alejandro Vallejo ◽  
Pilar Vizcarra ◽  
Carmen Quereda ◽  
Ana Moreno ◽  
Jose L Casado

Abstract Health care workers (HCW) are at an increased risk since they are directly exposed to SARS-CoV-2 infected patients, nevertheless, some remained without the development of anti-SARS-CoV-2 antibodies, suggesting lesser susceptibility to infection1-5. This study aimed to ascertain a potential specific cellular immune response to SARS-CoV-2 in these largely exposed HCWs.In this cross-sectional, case-control study, we analyzed 39 exposed uninfected HCWs and 17 convalescent HCWs. Cellular immune response was evaluated after SARS-CoV-2 stimulation with peptide pools (proteins S, M, and N), using bead-based multiplex assay (12 cytokines).Overall, 94.8% of uninfected HCWs had some degree of specific cellular response to SARS-CoV-2 structural proteins that could be classified, according to the number of cytokine production, as strong (61.5%), partial (33.3%), and weak/no response (5.1%). Strong responders showed a higher anti-inflammatory cytokine production (IL5 and IL10, p<0.001 and 0.002, respectively), and similar (IFN-γ and TNF-α, p=0.435 and 0.532, respectively) or higher (IL12, p=0.021) pro-inflammatory production compared to convalescents, resulted in a predominantly Th2 response. This study demonstrated a consistent and polyfunctional immune cellular response after stimulation with SARS-CoV-2 peptides in extensively exposed individuals that should be considered to establish the infection susceptibility, the impact in herd immunity, and the risk of relapses.


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.


2021 ◽  
Vol 15 (6) ◽  
pp. e0009378
Author(s):  
Ines Lakhal-Naouar ◽  
Rami Mukbel ◽  
Robert F. DeFraites ◽  
Rupal M. Mody ◽  
Lina N. Massoud ◽  
...  

Background Sand fly saliva exposure plays an important role in immunity against leishmaniasis where it has mostly been associated with protection. Phlebotomus (Ph.) alexandri transmits Leishmania (L.) infantum, the causative agent of visceral leishmaniasis (VL), in Iraq. Our group recently demonstrated that 20% of Operation Iraqi Freedom (OIF) deployers had asymptomatic VL (AVL) indicative of prior infection by the parasite L. infantum. Little is known about Ph. alexandri saliva, and the human immune response to it has never been investigated. Here, we characterize the humoral and cellular immune response to vector saliva in OIF deployers naturally exposed to bites of Ph. alexandri and characterize their immunological profiles in association to AVL. Methodology/Principal findings The humoral response to Ph. alexandri salivary gland homogenate (SGH) showed that 64% of 200 OIF deployers developed an antibody response. To assess the cellular immune response to saliva, we selected a subcohort of subjects based on their post-travel (median 4 months; range 1–22 months) antibody response (SGH Antibody [Ab] positive or negative) as well as their AVL status; ten never-traveled controls were also included. Banked peripheral blood mononuclear cells (PBMC), collected ~10 years after end of deployment, were stimulated with SGH for 96 hours. The levels of IFN- γ, IL-6, IL-10, IL-13 and IL-17 were determined by ELISA. Our findings indicate that OIF deployers mounted a cellular response to SGH where the anti-SGH+ asymptomatic subjects developed the highest cytokine levels. Further, stimulation with SGH produced a mixture of pro-inflammatory and anti-inflammatory cytokines. Contrary to our hypothesis, we observed no correlation between the cellular immune response to Ph. alexandri SGH and prevention from asymptomatic infection with L. infantum. Conclusions/Significance As we found, although all infected deployers demonstrated persistent disease control years after deployment, this did not correlate with anti-saliva systemic cellular response. More exposure to this vector may facilitate transmission of the L. infantum parasite. Since exposure to saliva of Ph. alexandri may alter the human immune response to bites of this vector, this parameter should be taken into consideration when considering the VL risk.


2020 ◽  
Author(s):  
Madhumita Shrotri ◽  
May C I van Schalkwyk ◽  
Nathan Post ◽  
Danielle Eddy ◽  
Catherine Huntley ◽  
...  

Introduction Understanding the cellular immune response to SARS-CoV-2 is critical to vaccine development, epidemiological surveillance and control strategies. This systematic review critically evaluates and synthesises the relevant peer-reviewed and pre-print literature published in recent months. Methods For this systematic review, independent keyword-structured literature searches were carried out in MEDLINE, Embase and COVID-19 Primer for studies published from 01/01/2020-26/06/2020. Papers were independently screened by two researchers, with arbitration of disagreements by a third researcher. Data were independently extracted into a pre-designed Excel template and studies critically appraised using a modified version of the MetaQAT tool, with resolution of disagreements by consensus. Findings were narratively synthesised. Results 61 articles were included. Almost all studies used observational designs, were hospital-based, and the majority had important limitations. Symptomatic adult COVID-19 cases consistently show peripheral T cell lymphopenia, which positively correlates with increased disease severity, duration of RNA positivity, and non-survival; while asymptomatic and paediatric cases display preserved counts. People with severe or critical disease generally develop more robust, virus-specific T cell responses. T cell memory and effector function has been demonstrated against multiple viral epitopes, and, cross-reactive T cell responses have been demonstrated in unexposed and uninfected adults, but the significance for protection and susceptibility, respectively, remains unclear. Interpretation A complex pattern of T cell response to SARS-CoV-2 infection has been demonstrated, but inferences regarding population level immunity are hampered by significant methodological limitations and heterogeneity between studies. In contrast to antibody responses, population-level surveillance of the cellular response is unlikely to be feasible in the near term. Focused evaluation in specific sub-groups, including vaccine recipients, should be prioritised.


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