Evaluation of age-related distribution of measles cases with primary and secondary immune response in Russian Federation, 2010-2016

In 2010—2016, blood serum samples were examined from 5539 patients, aged < 1—60 years, with clinically and laboratory confirmed measles. Primary or secondary type of immune response was determined for all measles cases. Studies were performed with children aged < 1—14 years (2381), adolescents, 15—17 years old (189), and adults aged 18—60 years (2969). Serum measles-specific IgM antibodies were measured by “VektoKor’ IgM” ELISA test system (Russia), concentration and avidity of specific IgG — by using “Anti-Measles Viruses ELISA/IgG” and “Avidity: Anti-Measles Viruses ELISA/ IgG” (Euroimmun, Germany). Primary immune response was identified based on the presence of serum measles-specific low avidity IgM and IgG antibodies, whereas secondary immune response was characterized by detecting high avidity IgM and IgG antibodies at concentration of ≥ 5.0 IU/ml. Analyzing measles-specific IgM antibodies in 2010—2016 demonstrated that measles morbidity was mainly due to children, aged 1—2 years reaching up to 39.9% of the total number of children with measles aged < 1—14 years as well as adults aged 18—40 years old comprising as high as 80.1% total number of patients aged 15—60 years. Serum measles-specific IgG testing showed that in 15.0% of cases they were detected at concentration of ≥ 5.0 IU/ml. Further serum dilution resulted in finding IgG titer ranging within 8.5—45.0 IU/ml (21.4+0.36) and high avidity antibodies in 80—100% (92.5+0.2) cases. The remaining 85.0% cases found low avidity measles-specific IgG antibodies (< 30%) at concentration of 0.2—3.46 IU/ml (1.73+0.03). An age-related analysis of our data demonstrated that all children under 14 with laboratory-confirmed measles developed primary immune response. Moreover, in 73.7% of measles patients aged 15—60 with primary immune response measles might be prevented by timely vaccination, whereas persons with “vaccine failure” comprised 26.3%. In 2010 (0.09 per 100,000 subjects) and 2016 (0.12 per 100,000 subjects), frequency of patients with “vaccine failure” during relative epidemic well-being was 35.3% and 18.2%, respectively, exceeding 9.9% (p < 0.001) serving as a hallmark 2014 high measles incidence rate (3.24 per 100,000 subjects).The data obtained indicate that measles virus circulate among people with “vaccine failure,” which may account for potential to spread and infect unprotected population cohorts as well as cause measles outbreaks during periods of epidemic well-being.

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Measles in bone marrow transplant recipients during an outbreak in São Paulo, Brazil

Blood ◽

10.1182/blood.v99.1.83 ◽

2002 ◽

Vol 99 (1) ◽

pp. 83-87 ◽

Cited By ~ 56

Author(s):

Clarisse M. Machado ◽

Flávio B. Gonçalves ◽

Cláudio S. Pannuti ◽

Frederico L. Dulley ◽

Vanda A. U. F. de Souza

Keyword(s):

Bone Marrow ◽

Immune Response ◽

Marrow Transplant ◽

First Year ◽

High Avidity ◽

Secondary Immune Response ◽

Measles Vaccine ◽

Transplant Recipients ◽

Igg Antibodies ◽

Measles Outbreak

In 1997, a measles outbreak was identified in São Paulo. Between February and December, 20 185 cases were confirmed. From April to July 1997, a seroepidemiologic survey was conducted to identify the recipients of bone marrow (BM) transplants who were susceptible to measles and the occurrence of measles in this population. A total of 156 patients were screened by enzyme immunoassay (EIA). Patients with IgG titers more than 100 mIU/mL were considered immune. Measles reimmunization records were also reviewed. Thirty-two vaccinated patients underwent serologic evaluation. Six of 22 patients (27.3%) within 3 years after vaccination lost measles immunity, in contrast to 7 of 10 patients (70%) vaccinated longer than 3 years previously (P = .049). Among the 122 nonvaccinated patients, 41 (33.6%) were susceptible to measles: 4 of 47 patients (8.5%) within the first year after BM transplantation (BMT), and 37 of the 75 patients (49.3%) after the first year after BMT (P < .001). Eight recipients acquired measles, confirmed by serology (EIA). High-avidity IgG antibodies were observed in the acute phase of measles, suggesting a secondary immune response. Measles interstitial pneumonia was observed in one patient. Seven patients had mild symptoms. Exanthema was present in all patients. All but one patient had fever and nonproductive cough. Koplik spots could be observed in 5 patients. Measles can be mild in BM transplant recipients. Exanthema is frequently present but not often typical. Immunity to measles decreases after day +365 after BMT. Additional studies are needed to evaluate the safety of measles vaccine after the first year of BMT, mostly during outbreaks.

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Identification of Primary and Secondary Measles Vaccine Failures by Measurement of Immunoglobulin G Avidity in Measles Cases during the 1997 São Paulo Epidemic

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.11.1.119-122.2004 ◽

2004 ◽

Vol 11 (1) ◽

pp. 119-122 ◽

Cited By ~ 51

Author(s):

Cláudio S. Pannuti ◽

Ricardo José Morello ◽

José Cássio de Moraes ◽

Suely Pires Curti ◽

Ana Maria S. Afonso ◽

...

Keyword(s):

Immune Response ◽

Immunoglobulin M ◽

Primary Immune Response ◽

Secondary Immune Response ◽

Measles Vaccine ◽

Vaccine Failure ◽

Avidity Index ◽

Control Programs ◽

Igg Avidity ◽

Vaccine Failures

ABSTRACT Despite almost universal use of measles vaccines in recent decades, epidemics of the disease continue to occur. Understanding the role of primary vaccine failure (failure to seroconvert after vaccination) and secondary vaccine failures (waning immunity after seroconversion) in measles epidemics is important for the evaluation of measles control programs in developing countries. After a measles epidemic in São Paulo, Brazil, 159 cases previously confirmed by detection of specific immunoglobulin M (IgM) antibodies were tested for IgG avidity, and a secondary immune response, defined by an IgG avidity index of at least 30%, was established in 30 of 159 (18.9%) patients. Among the 159 patients, 107 (67.3%) had not been vaccinated and 52 (32.7%) had received one or more doses of measles vaccine. Of the 107 unvaccinated patients, 104 (97.2%) showed a primary immune response, defined as an IgG avidity index of less than 30%. Among the 52 patients with documented vaccination, 25 (48.1%) showed a primary immune response and 27 (51.9%) showed a secondary immune response, thereby constituting a secondary vaccine failure. Primary vaccine failure was observed in 13 of 13 patients vaccinated prior to 1 year of age and in 43.5 and 12.5%, respectively, of patients receiving one or two doses after their first birthdays. These results provide evidence that measurement of IgG avidity can be used to distinguish between primary and secondary vaccine failures in vaccinated patients with measles; the method can also be a useful tool for the evaluation of measles control programs.

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Endogenously Produced SARS-CoV-2 Specific IgG Antibodies May Have a Limited Impact on Clearing Nasal Shedding of Virus during Primary Infection in Humans

Viruses ◽

10.3390/v13030516 ◽

2021 ◽

Vol 13 (3) ◽

pp. 516

Author(s):

Shuyi Yang ◽

Keith R. Jerome ◽

Alexander L. Greninger ◽

Joshua T. Schiffer ◽

Ashish Goyal

Keyword(s):

Production Rate ◽

Neutralizing Antibodies ◽

Primary Infection ◽

Natural Infection ◽

Viral Clearance ◽

Clinical Severity ◽

Igg Antibodies ◽

Igm Antibodies ◽

Specific Igg ◽

Specific Igg Antibodies

While SARS-CoV-2 specific neutralizing antibodies have been developed for therapeutic purposes, the specific viral triggers that drive the generation of SARS-CoV-2 specific IgG and IgM antibodies remain only partially characterized. Moreover, it is unknown whether endogenously derived antibodies drive viral clearance that might result in mitigation of clinical severity during natural infection. We developed a series of non-linear mathematical models to investigate whether SARS-CoV-2 viral and antibody kinetics are coupled or governed by separate processes. Patients with severe disease had a higher production rate of IgG but not IgM antibodies. Maximal levels of both isotypes were governed by their production rate rather than different saturation levels between people. Our results suggest that an exponential surge in IgG levels occurs approximately 5–10 days after symptom onset with no requirement for continual antigenic stimulation. SARS-CoV-2 specific IgG antibodies appear to have limited to no effect on viral dynamics but may enhance viral clearance late during primary infection resulting from the binding effect of antibody to virus, rather than neutralization. In conclusion, SARS-CoV-2 specific IgG antibodies may play only a limited role in clearing infection from the nasal passages despite providing long-term immunity against infection following vaccination or prior infection.

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Development of SARS-CoV-2 Specific IgG and Virus-Neutralizing Antibodies after Infection with Variants of Concern or Vaccination

Vaccines ◽

10.3390/vaccines9070700 ◽

2021 ◽

Vol 9 (7) ◽

pp. 700

Author(s):

Franziska Neumann ◽

Ruben Rose ◽

Janine Römpke ◽

Olaf Grobe ◽

Thomas Lorentz ◽

...

Keyword(s):

Immune Response ◽

Receptor Binding ◽

Neutralizing Antibodies ◽

Neutralization Test ◽

Vaccine Dose ◽

High Avidity ◽

Receptor Binding Domain ◽

Robust Immune Response ◽

Specific Igg ◽

Nucleoprotein N

The humoral immunity after SARS-CoV-2 infection or vaccination was examined. Convalescent sera after infection with variants of concern (VOCs: B.1.1.7, n = 10; B.1.351, n = 1) and sera from 100 vaccinees (Pfizer/BioNTech, BNT162b2, n = 33; Moderna, mRNA-1273, n = 11; AstraZeneca, ChAdOx1 nCoV-19/AZD1222, n = 56) were tested for the presence of immunoglobulin G (IgG) directed against the viral spike (S)-protein, its receptor-binding domain (RBD), the nucleoprotein (N) and for virus-neutralizing antibodies (VNA). For the latter, surrogate assays (sVNT) and a Vero-cell based neutralization test (cVNT) were used. Maturity of IgG was determined by measuring the avidity in an immunoblot (IB). Past VOC infection resulted in a broad reactivity of anti-S IgG (100%), anti-RBD IgG (100%), and anti-N IgG (91%), while latter were absent in 99% of vaccinees. Starting approximately two weeks after the first vaccine dose, anti-S IgG (75–100%) and particularly anti-RBD IgG (98–100%) were detectable. After the second dose, their titers increased and were higher than in the convalescents. The sVNT showed evidence of VNA in 91% of convalescents and in 80–100%/100% after first/second vaccine dose, respectively. After the second dose, an increase in VNA titer and IgGs of high avidity were demonstrated by cVNT and IB, respectively. Re-vaccination contributes to a more robust immune response.

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Enhanced immunogenicity of a synthetic DNA vaccine expressing consensus SARS-CoV-2 Spike protein using needle-free immunization

10.1101/2021.02.01.429219 ◽

2021 ◽

Author(s):

Sawsan S Alamri ◽

Khalid A Alluhaybi ◽

Rowa Y Alhabbab ◽

Abdullah Algaissi ◽

Sarah Almahboub ◽

...

Keyword(s):

Immune Response ◽

Dna Vaccine ◽

Mammalian Cells ◽

Cellular Response ◽

Igg Antibodies ◽

Free System ◽

Mammalian Expression ◽

Specific Igg ◽

Needle Injection ◽

Specific Igg Antibodies

AbstractThe ongoing global pandemic of Coronavirus Disease 2019 (COVID-19) calls for an urgent development of effective and safe prophylactic and therapeutic measures. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein is a major immunogenic and protective protein, and plays a crucial role in viral pathogenesis. In this study, we successfully constructed a synthetic codon-optimized DNA-based vaccine as a countermeasure against SARS-CoV-2; denoted as VIU-1005. The design was based on the synthesis of codon-optimized coding sequence for optimal mammalian expression of a consensus full-length S glycoprotein. The successful construction of the vaccine was confirmed by restriction digestion and sequencing, and the protein expression of the S protein was confirmed by western blot and immunofluorescence staining in mammalian cells. The immunogenicity of the vaccine was tested in two mouse models (BALB/c and C57BL/6J). Th1-skewed systemic S-specific IgG antibodies and neutralizing antibodies (nAbs) were significantly induced in both models four weeks post three injections with 100 μg of the VIU-1005 vaccine via intramuscular needle injection but not intradermal or subcutaneous routes. Importantly, such immunization induced long-lasting IgG response in mice that lasted for at least 6 months. Interestingly, using a needle-free system, we showed an enhanced immunogenicity of VIU-1005 in which lower doses such as 25-50 μg or less number of doses were able to elicit significantly high levels of Th1-biased systemic S-specific IgG antibodies and nAbs via intramuscular immunization compared to needle immunization. Compared to the intradermal needle injection which failed to induce any significant immune response, intradermal needle-free immunization elicited robust Th1-biased humoral response similar to that observed with intramuscular immunization. Furthermore, immunization with VIU-1005 induced potent S-specific cellular response as demonstrated by the significantly high levels of IFN-γ, TNF and IL-2 cytokines production in memory CD8+ and CD4+ T cells in BALB/c mice. Together, our results demonstrate that the synthetic VIU-1005 candidate DNA vaccine is highly immunogenic and capable of inducing long-lasting and Th1-skewed immune response in mice. Furthermore, we show that the use of needle-free system could enhance the immunogenicity and minimize doses needed to induce protective immunity in mice, supporting further preclinical and clinical testing of this candidate vaccine.

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CMV-Specific Immune Response—New Patients, New Insight: Central Role of Specific IgG during Infancy and Long-Lasting Immune Deficiency after Allogenic Stem Cell Transplantation

International Journal of Molecular Sciences ◽

10.3390/ijms20020271 ◽

2019 ◽

Vol 20 (2) ◽

pp. 271 ◽

Cited By ~ 3

Author(s):

Przemyslaw Zdziarski

Keyword(s):

Immune Response ◽

Nk Cells ◽

Cellular Immune Response ◽

Specific Immune Response ◽

Primary Immune Response ◽

Virus Reactivation ◽

Allogenic Stem Cell Transplantation ◽

Specific Igg ◽

Cellular Immune

Although the existing paradigm states that cytomegalovirus (CMV) reactivation is under the control of the cellular immune response, the role of humoral and innate counterparts are underestimated. The study analyzed the host–virus interaction i.e., CMV-immune response evolution during infection in three different clinical situations: (1) immunodeficient CMV-positive human leukocyte antigen (HLA)-matched bone marrow recipients after immunoablative conditioning as well as immunocompetent, (2) adult, and (3) infant with primary immune response. In the first situation, a fast and significant decrease of specific immunity was observed but reconstitution of marrow-derived B and natural killer (NK) cells was observed prior to thymic origin of T cells. The lowest CMV-IgG (93.2 RU/mL) was found just before CMV viremia. It is noteworthy that the sole and exclusive factor of CMV-specific immune response is a residual recipient antibody class IgG. The CMV-quantiferon increase was detected later, but in the first phase, phytohemagglutinin (PHA)-induced IFN-γ release was significantly lower than that of CMV-induced (“indeterminate” results). It corresponds with the increase of NK cells at the top of lymphocyte reconstitution and undetected CMV-specific CD8 cells using a pentamer technique. In immunocompetent adult (CMV-negative donor), the cellular and humoral immune response increased in a parallel manner, but symptoms of CMV mononucleosis persisted until the increase of specific IgG. During infancy, the decrease of the maternal CMV-IgG level to 89.08 RU/mL followed by clinical sequel, i.e., CMV replication, were described. My observations shed light on a unique host-CMV interaction and CMV-IgG role: they indicate that its significant decrease predicts CMV replication. Before primary cellular immune response development, the high level of residual CMV-IgG (about >100 R/mL) from mother or recipient prevents virus reactivation. The innate immune response and NK-dependent IFN-secretion should be further investigated.

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Paraquat Preferentially Induces Apoptosis of Late Stage Effector Lymphocyte and Impairs Memory Immune Response in Mice

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16112060 ◽

2019 ◽

Vol 16 (11) ◽

pp. 2060 ◽

Cited By ~ 4

Author(s):

Yiming Shao ◽

Yifan Zhao ◽

Tingting Zhu ◽

Fen Zhang ◽

Xiuli Chang ◽

...

Keyword(s):

Immune Response ◽

Late Stage ◽

Early Stage ◽

Keyhole Limpet Hemocyanin ◽

Primary Immune Response ◽

Secondary Immune Response ◽

Effector Cells ◽

Memory Immune Response ◽

The Impact

Paraquat (PQ) is a toxic non-selective herbicide. To date, the effect of PQ on memory immune response is still unknown. We investigated the impact of PQ on memory immune response. Adult C57BL/6 mice were subcutaneously injected with 2 mg/kg PQ, 20 mg/kg PQ or vehicle control every three days for two weeks. A single injection of keyhole limpet hemocyanin (KLH) at day four after the initial PQ treatment was used to induce a primary immune response; a second KLH challenge was performed at three months post the first KLH immunization to induce a secondary immune response. In steady state, treatment with 20 mg/kg PQ reduced the level of serum total IgG, but not that of IgM; treatment with 20 mg/kg PQ decreased the number of effector and memory lymphocytes, but not naïve or inactivated lymphocytes. During the primary immune response to KLH, treatment with 20 mg/kg PQ did not influence the proliferation of lymphocytes or expression of co-stimulatory molecules. Instead, treatment with 20 mg/kg PQ increased the apoptosis of lymphocytes at late stage, but not early stage of the primary immune response. During the secondary immune response to KLH, treatment with 20 mg/kg PQ reduced the serum anti-KLH IgG and KLH-responsive CD4 T cells and B cells. Moreover, effector or activated lymphocytes were more sensitive to PQ-induced apoptosis in vitro. Treatment with 2 mg/kg PQ did not impact memory immune response to KLH. Thus, treatment with 20 mg/kg PQ increased apoptosis of late stage effector cells to yield less memory cells and thereafter impair memory immune response, providing a novel understanding of the immunotoxicity of PQ.

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T Cell Mediated Antibody lnvariance in an Immune Response Against A Bacterial Carbohydrate Antigen Requires CD28/B7–1 Costimulation

Developmental Immunology ◽

10.1155/2001/87168 ◽

2001 ◽

Vol 8 (3-4) ◽

pp. 243-257 ◽

Cited By ~ 2

Author(s):

André Rademaekers ◽

Eckehart Kölsch ◽

Christoph Specht

Keyword(s):

Immune Response ◽

T Cells ◽

B Cells ◽

Clonal Expansion ◽

Carbohydrate Antigen ◽

Igg Antibodies ◽

Humoral Immune ◽

Specific Igg ◽

The One ◽

First Time

The humoral immune response againstα(1→3)dextran (Dex) in BALB/c mice is characterized by the formation of predominantly IgM antibodies bearing the J558 idiotype. IgG antibodies do not appear in euthymic mice. In athymic animals however, the response proceeds to a vigorous IgG production. In euthymic mice formation of IgG is suppressed by J558 idiotype- specific regulatory T cells recognizing in association with I-Edand in cognate T/B interaction the VH CDR3 derived peptide of the J558 idiotpye. Only B-2 lymphocytes produce IgG whereas B-1 cells do not participate in the production of this Ig class. Using a novel synthetic allα(1→3)-D-gluco configurated tetrasaccharide the Dex-specific B cells can for the first time be analyzed in FACS. In experiments using this newly designed low molecular Dex no signs of B cell apoptosis can be found. This demonstrates a true silencing of persisting Bγ memory cells and supports previous by adoptive transfer experiments. In this suppression an involvement of CD28/B7–1 interaction can be demonstrated which is a necessary costimulatory suppression signal in addition to the cognate TCR/peptide-I-Edinteraction between J558 Id-specific T cells and J558 idiotype beating B cells. This results in an activation of 178–4 Ts cells, leading to an overall suppression of the Dex-specific IgG isotype production on the one hand and on the other hand provides a signal for the survival and clonal expansion of J558 Id-positive B cells.

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Antibody response to SARS-CoV-2 infection and BNT162b2 vaccine in Israel

10.1101/2021.07.07.21259499 ◽

2021 ◽

Author(s):

Guy Shapira ◽

Ramzia Abu Hamad ◽

Chen Weiner ◽

Nir Rainy ◽

Reut Sorek-Abramovich ◽

...

Keyword(s):

Immune Response ◽

Viral Entry ◽

Neutralizing Antibodies ◽

Host Cells ◽

Spike Protein ◽

Igg Antibodies ◽

Age And Gender ◽

Specific Igg ◽

And Gender ◽

Specific Igg Antibodies

Neutralizing antibodies targeting the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) block viral entry to host cells, preventing disease and further spread of the pathogen. The presence of SARS-CoV-2 antibodies in serum is a reliable indicator of infection, used epidemiologically to estimate the prevalence of infection and clinically as a measurement of an antigen-specific immune response. In this study, we analyzed serum Spike protein-specific IgG antibodies from 26,170 samples, including convalescent individuals who had coronavirus disease 2019 (COVID-19) and recipients of the BNT162b2 vaccine. We find distinct serological patterns in COVID-19 convalescent and vaccinated individuals, correlated with age and gender and the presence symptoms.

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