scholarly journals Humoral and cellular immunity to measles and rubella virus antigens in healthy subjects

2019 ◽  
Vol 9 (3-4) ◽  
pp. 607-611 ◽  
Author(s):  
M. A. Smerdova ◽  
A. P. Toptygina ◽  
Yu. Yu. Andreev ◽  
S. V. Sennikova ◽  
A. Yu. Zetkin ◽  
...  

An issue of eradicating measles and rubella virus-induced infections currently remains unresolved, despite existing effective methods for specific prophylaxis and WHO’s commitment to a mass vaccination policy. While improving epidemic situation, analysis of new challenges, such as measles incidence in adults, especially in adults vaccinated in childhood, is of particular interest. The aim of the study was to analyze serum measles and rubella virus-specific IgG antibodies in young healthy people and estimate antigen-specific cellular immune response in seronegative subjects. There were examined 100 healthy adults aged 18–30 years old. Level of serum specific IgG was measured by ELISA (Vector-Best, Russia). Antigen-specific cellular immune response was assessed by magnitude of surface CD107a expression on CD8hi T cells challenged by measles and rubella virus-derived antigens. It was found that average level of antibodies against rubella virus comprised 175.5 IU/ml, 49% of which recovered after rubella, 46% were vaccinated, whereas 5% subjects contained no virus-specific antibodies. In addition, mean level of anti-measles virus antibodies was below protective magnitude, among which 1% subjects recovered after measles, 31% displayed post-vaccination immunity, 55% subjects were seronegative, and 13% had equivocal levels of specific antibodies. Thus, 68% subjects were unprotected against measles virus based on the level of serum virus-specific antibodies. Moreover, 40 out of 68 subjects were vaccinated against measles in childhood. Additional screening adult subjects for intensity of measles and rubella virus-specific cellular immunity demonstrated that 57.37% of them contained peripheral blood CD8 T cells against measles virus and 59.01% — against rubella virus. Further analysis allowed to identify 4 subgroups displaying: 1) high level of virus-specific antibodies and T cells; 2) neither antibodies nor specific T-cells reaching as low as 20% of baseline group; 3) high antibody level combined with low amount of specific T cells; and 4) low antibody level combined with high level of specific T cells. thus, it may be assumed that cellular and humoral immune arms are maintained independently and being active for a long term after vaccination. Preserving a specific T-cell immunity seems to provide protection against infection, thereby accounting for the lack of measles manifestation in all seronegative subjects. 

2004 ◽  
Vol 189 (7) ◽  
pp. 1199-1208 ◽  
Author(s):  
Annette Oxenius ◽  
David A. Price ◽  
Martin Hersberger ◽  
Erika Schlaepfer ◽  
Rainer Weber ◽  
...  

2020 ◽  
Author(s):  
Nina Le Bert ◽  
Hannah E Clapham ◽  
Anthony T Tan ◽  
Wan Ni Chia ◽  
Christine YL Tham ◽  
...  

AbstractThe efficacy of virus-specific T cells in clearing pathogens involves a fine balance between their antiviral and inflammatory features. SARS-CoV-2-specific T cells in individuals who clear SARS-CoV-2 infection without symptoms or disease could reveal non-pathological yet protective characteristics. We therefore compared the quantity and function of SARS-CoV-2-specific T cells in a cohort of asymptomatic individuals (n=85) with that of symptomatic COVID-19 patients (n=76), at different time points after antibody seroconversion. We quantified T cells reactive to structural proteins (M, NP and Spike) using ELISpot assays, and measured the magnitude of cytokine secretion (IL-2, IFN-γ, IL-4, IL-6, IL-1β, TNF-α and IL-10) in whole blood following T cell activation with SARS-CoV-2 peptide pools as a functional readout. Frequencies of T cells specific for the different SARS-CoV-2 proteins in the early phases of recovery were similar between asymptomatic and symptomatic individuals. However, we detected an increased IFN-γ and IL-2 production in asymptomatic compared to symptomatic individuals after activation of SARS-CoV-2-specific T cells in blood. This was associated with a proportional secretion of IL-10 and pro-inflammatory cytokines (IL-6, TNF-α and IL-1β) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2-specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2 infected individuals are not characterized by a weak antiviral immunity; on the contrary, they mount a robust and highly functional virus-specific cellular immune response. Their ability to induce a proportionate production of IL-10 might help to reduce inflammatory events during viral clearance.


2021 ◽  
Vol 218 (5) ◽  
Author(s):  
Nina Le Bert ◽  
Hannah E. Clapham ◽  
Anthony T. Tan ◽  
Wan Ni Chia ◽  
Christine Y.L. Tham ◽  
...  

The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between antiviral and inflammatory features. SARS-CoV-2–specific T cells in individuals who clear SARS-CoV-2 without symptoms could reveal nonpathological yet protective characteristics. We longitudinally studied SARS-CoV-2–specific T cells in a cohort of asymptomatic (n = 85) and symptomatic (n = 75) COVID-19 patients after seroconversion. We quantified T cells reactive to structural proteins (M, NP, and Spike) using ELISpot and cytokine secretion in whole blood. Frequencies of SARS-CoV-2–specific T cells were similar between asymptomatic and symptomatic individuals, but the former showed an increased IFN-γ and IL-2 production. This was associated with a proportional secretion of IL-10 and proinflammatory cytokines (IL-6, TNF-α, and IL-1β) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2–specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2–infected individuals are not characterized by weak antiviral immunity; on the contrary, they mount a highly functional virus-specific cellular immune response.


2017 ◽  
Vol 41 (2) ◽  
pp. 423-438 ◽  
Author(s):  
Quanhui Tan ◽  
Siyuan Ma ◽  
Jianjun Hu ◽  
Xiaohua Chen ◽  
Yongsheng Yu ◽  
...  

Background: Chronic hepatitis B virus (HBV) infection is associated with a weak but specific cellular immune response of the host to HBV. Tripeptidyl peptidaseⅡ (TPPⅡ), an intracellular macromolecule and proteolytic enzyme, plays an important complementary and compensatory role for the proteasome during viral protein degradation and major histocompatibility complex class I antigen presentation by inducing a specific cellular immune response in vivo. Based on a previous study, we aimed to explore the role of MHC class I antigen presentation in vivo and the mechanisms that may be involved. Methods: In this study, recombinant adenoviral vectors harboring the hepatitis B core antigen (HBcAg) and the TPPII gene were constructed (Adv-HBcAg and Adv-HBcAg-TPPII), and H-2Kd HBV-transgenic BALB/c mice and HLA-A2 C57BL/6 mice were immunized with these vectors, respectively. We evaluated the specific immune responses induced by Adv-HBcAg-TPPII in the HBV transgenic BALB/c mice and HLA-A2 C57BL/6 mice as well as the anti-viral ability of HBV transgenic mice, and we explored the underlying mechanisms. Results: We found that immunization with Adv-HBcAg-TPPII induced the secretion of the cytokines interleukin-2 (IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) as well as the activities of IFN-γ-secreting CD8+ T cells and CD4+ T cells. In addition, HBcAg-specific CTL activity in C57/BL mice and HBV transgenic animals was significantly enhanced in the Adv-HBcAg-TPPII group. Furthermore, Adv-HBcAg-TPPII decreased the hepatitis B surface antigen (HBsAg) and HBV DNA levels and the amount of HBsAg and HBcAg in liver tissues. Moreover, Adv-HBcAg-TPPII enhanced the expression of T-box transcription factor (T-bet) and downregulated GATA-binding protein 3 (GATA-3) while increasing the expression levels of JAK2, STAT1, STAT4 and Tyk2. Conclusions: These results suggested that the JAK/STAT signaling pathway participates in the CTL response that is mediated by the adenoviral vector encoding TPPII. Adv-HBcAg-TPPII could therefore break immune tolerance and stimulate HBV-specific cytotoxic T lymphocyte activity and could have a good therapeutic effect in transgenic mice.


2020 ◽  
Vol 10 (1) ◽  
pp. 137-144
Author(s):  
A. P. Toptygina ◽  
Yu. Yu. Andreev ◽  
M. A. Smerdova ◽  
A. Yu. Zetkin ◽  
T. G. Klykova

Despite adherence to the policy of mass measles vaccination in the majority of countries, this infection still remains far from being fully eradicated. Measles outbreaks are reported worldwide, when the vast majority of cases are recorded in subjects of 18—35 years of age. Studies on assessing measles IgG antibody level in different regions of Russia reveal increased percentage of measles seronegative subjects among young adults. Current study was aimed at investigating formation of humoral and cellular immunity after measles vaccination in seronegative adults aged 18 to 30 years old. There were enrolled 50 measles seronegative healthy volunteers aged 18 to 30 years old. Level of anti-measles IgM and IgG antibodies was measured by ELISA (Vector-Best, Russia). Subclasses of measles specific IgG antibodies were analyzed by ELISA, by replacing IgG conjugate for IgG1, IgG2, IgG3, IgG4 conjugates, whereas measles specific IgA antibodies were estimated by ELISA with IgA conjugate (Polygnost, Russia) at a concentration of 1 μg/ml. Antibody avidity was assessed by ELISA (Euroimmun, Germany). Cell-mediated measles immunity was estimated by CD107a surface expression on CD8hi T cell subset stimulated by measles virus-derived antigens. A specific cellular response to measles antigens before vaccination was detected in 50% of examined subjects, whereas 40% samples showed no signs of cellular immune response, with 10% of remaining cases described as equivocal. It was found that 6 weeks after vaccination all vaccinated subjects developed measles specific IgG antibodies at protective level reaching 1.33 (0.85—1.82) IU/ml [Me (LQ—UQ)]. Anti-measles IgA antibodies were of 0.655 (0.423—1.208) IU/ml [Me (LQ—UQ)]. However, no measles specific IgM antibodies were detected 6 weeks after vaccination. In addition, primary type of immune response (dominant low-avidity anti-measles antibodies IgG3 subclass) to measles vaccination was observed in 24 out of 50 subjects, whereas 26 subjects developed secondary type of immune response (high-avidity anti-measles antibodies dominated by IgG1 subclass). A measles specific cellular immune response was observed in 47 of the 50 examined subjects, and in 3 volunteers it was equivocal. Further analysis revealed a cohort of subjects who were not vaccinated against measles (18 subjects), although 60% of them provided medical record on previous dual measles vaccination occurred in childhood. Another cohort consisted of subjects who had medical record of measles vaccination in childhood (32 subjects), but lost protective measles antibodies produced by plasma cells (23 subjects), and memory T cells (3 subjects), or measles antibodies and memory B cells (6 subjects) over time. Such pattern evidences that measles-specific cellular and humoral arms immune responses were developed and maintained independently of each other.


2021 ◽  
Author(s):  
Cheng-Wei Chang ◽  
Yuchen Liu ◽  
Cheng Jiao ◽  
Hongwei Liu ◽  
Xiaochuan Chen ◽  
...  

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific cellular immune response may prove to be essential for long-term immune protection against the novel coronavirus disease 2019 (COVID-19). To assess COVID-19-specific immunity in the population, we synthesized selected peptide pools of SARS-CoV-2 structural and functional proteins, including Spike (S), Membrane (M), Envelope (E), Nucleocapsid (N) and Protease (P) as target antigens. Survey of the T cell precursur frequencies in healthy individuals specific to these viral antigens demonstrated a diverse cellular immunity, including high, medium, low and no responders. This was further confirmed by in vitro induction of anti-SARS-CoV-2 T cell immune responses using dendritic cell (DC)/T cell coculture, which supported the corresponding T cell precursor frequencies in each of the individuals tested. In general, the combination of all five viral antigen pools induced the strongest cellular immune response, yet individual donors responded differently to different viral antigens. Importantly, in vitro restimulation of the T cells with the DC-peptides induced increased anti-viral immune responses in all individuals even in the no responders, suggesting that repeated antigen stimulation could elicit a broad protection in immune naïve population. Our analysis recapitulates the critical role of cellular immunity in fighting COVID-19 and the importance of analyzing anti-SARS-CoV-2 T cell response in addition to antibody response in the population.ImportanceFacing the rapid evolving SARS-CoV-2 variants in the world, current emphasis on antibody-producing vaccines needs a quick revisit. The virus-specific cellular immunity may prove to be essential for long-term protection against COVID-19. This study designed a series of antigenic peptides encompassing the conserved and/or essential domains of Spike (S), Membrane (M), envelope (E), Nucleocapsid (N) and Protease (P) as targets to assess Covid-19-specific immunity in the population. The results demonstrated a diverse cellular immunity, including high, medium, low and no responders. This was verified by in vitro generation of anti-SARS-CoV-2 T-cells from these subjects. The study suggested that individuals responded differently to the different viral antigens, and importantly, repeated stimulation could produce virus specific T cells in all individuals, including the no responders. This study illustrates the needs for assessing anti-viral cellular immunity in addition to antibody response in the general population.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexandra J. Spencer ◽  
Paul F. McKay ◽  
Sandra Belij-Rammerstorfer ◽  
Marta Ulaszewska ◽  
Cameron D. Bissett ◽  
...  

AbstractSeveral vaccines have demonstrated efficacy against SARS-CoV-2 mediated disease, yet there is limited data on the immune response induced by heterologous vaccination regimens using alternate vaccine modalities. Here, we present a detailed description of the immune response, in mice, following vaccination with a self-amplifying RNA (saRNA) vaccine and an adenoviral vectored vaccine (ChAdOx1 nCoV-19/AZD1222) against SARS-CoV-2. We demonstrate that antibody responses are higher in two-dose heterologous vaccination regimens than single-dose regimens. Neutralising titres after heterologous prime-boost were at least comparable or higher than the titres measured after homologous prime boost vaccination with viral vectors. Importantly, the cellular immune response after a heterologous regimen is dominated by cytotoxic T cells and Th1+ CD4 T cells, which is superior to the response induced in homologous vaccination regimens in mice. These results underpin the need for clinical trials to investigate the immunogenicity of heterologous regimens with alternate vaccine technologies.


2020 ◽  
Vol 10 (2) ◽  
pp. 375-380
Author(s):  
A. G. Sonis ◽  
O. A. Gusyakova ◽  
F. N. Gilmiyarova ◽  
A. A. Ereshchenko ◽  
N. K. Ignatova ◽  
...  

Epidemiological situation describing global measles spread is ambiguous. Along with countries succeeded in measles eradication, there are those wherein measles rate remains at quite high level. Because measles is a vaccine-preventable infection, it may then be eradicated solely by ensuring sufficient population coverage with preventive vaccination. The aim of our study was to assess level of measles immunity in medical workers at the Clinics of Samara State Medical University as well as the Samara State Medical University. There were enrolled 1503 subjects (aged 18–79 years), among which all individuals under 55 (77.58%) but not older counterparts provided with medical record on previous measles vaccination or measles infection. Level of serum measles virus-specific IgG antibodies was measured by using ELISA (VektoKor-IgG, JSC Vector-Best, Novosibirsk), with mean concentration ranging in general population within 1.02±0.02 IU/ ml. Positive results were observed in 72.52% of the examined individuals. Average vs. high measles virus-specific IgG level was detected in 52.90% (mean age — 41.4±0.5 years) and 19.62% (mean age — 54.2±0.72 years) of individuals, whereas at level below threshold — in 27.48% of subjects (mean age — 33.25±0.53 years). Thus, in 34.16% of the surveyed vaccinated individuals mostly presented by young subjects contained anti-measles virus-specific antibodies below protective level. Older age groups were shown to increase in average IgG amount with age. Interestingly, age-related measles immunity pattern was observed: percentage of subjects with high vs. low measles virus-specific IgG level increases and decreases, respectively. Taking into consideration a large percentage of subjects previously vaccinated against measles among carriers of low measles immunity, it may be concluded that measles virus-specific IgG antibody level must be monitored in young adulthood to decide of whether subsequent revaccination is necessary.


2020 ◽  
Vol 22 (4) ◽  
pp. 799-804
Author(s):  
L. P. Sizyakina ◽  
I. I. Andreeva ◽  
D. I. Danilova

Lifetime use of IgG replacement therapy  is the standard of CVID treatment. However, full control over stabilization of chronic infection loci is not always achieved, even if this therapy  is continuously applied. The purpose  of this study was to carry out comparative analysis of changes  in cellular  component of adaptive and  innate immune response, depending on effectiveness of replacement therapy  of patients with infectious CVID  phenotype. The  observation group  consisted of 15 patients with  CVID  who  were  diagnosed since early childhood in 100% of cases. They had prolonged respiratory infections followed by the development of complications requiring continuous treatment with antibiotics.After  reaching mean  age of 15 years  old,  the  intensity of infection-associated antibody deficiency was 6-8  times  per year. After verification of the  diagnosis, the  patients received  replacement therapy, first at the saturation dose,  and,  after stabilization of IgG  at the level of 7-8 g/l,  at the monthly maintenance dose. The clinical  course  of the disease was traced  during  a full year of replacement therapy, and the cellular  immunity indices  were evaluated. In all patients, after a year of therapy  corresponding to clinical  guidelines, there  was an improvement in quality  of life indices, decreased rates of recurrent bacterial infections. At the same time, 40% of them continued to suffer, on average, 5.4±1.1 times a year and required long-term courses of antibiotic therapy. Evaluation of immune status did not reveal statistically significant  differences in IgG plasma saturation between the groups of patients with different treatment efficiency: 8.7 (8-9) g/l and 9.1 (8.5-10.5) g/l, at p = 0.5. The  differences related  to immune cell factors  in cases of smaller  effect of IVIG  therapy  are manifested in higher  relative  numbers of T effectors  containing lytic Granzyme B granules  and CD14+CD284+  monocytes, accompanied by lower spontaneous active  oxygen forms produced by neutrophils, lesser contents of CD16+ natural killers in peripheral blood.The obtained data illustrate the value of monitoring, not only serum  IgG  level, but also the parameters of the  cellular  immune response. Such  analysis  may be essential  as a prognostic criterion for efficacy  of IVIG therapy. Reduced levels of some parameters of innate immunity cells serves a basis to formulate the concept of combined treatment and usage of tools that alter functions of immunocompetent cells.


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