Avidity Of IgG Antibodies Research Articles

Replication, safety and immunogenicity of the vectored Ebola vaccine rVSV-ΔG-ZEBOV-GP in a sub-Saharan African paediatric population: A randomised controlled, open-label trial in children aged 1-12 years living in Lambaréné, Gabon

Unlike adults, children experienced stronger and longer vector replication in plasma and shedding in saliva following rVSVΔG-ZEBOV-GP vaccination. The resulting risks of immunosuppression or immune hyperactivation leading to increased Adverse Events (AEs) and altered antibody responses are concerns that have been addressed in the present manuscript. Children aged 1-12 years living in Gabon received either rVSVΔG-ZEBOV-GP (ERVEBO®) vaccine or the varicella-zoster virus (VZV) vaccine (VZV). The concentration of rVSVΔG vector in blood and saliva, the occurrence of AEs up to day 28; the anti-rVSVΔG-ZEBOV-GP and anti-VZV IgG antibody titres, neutralising and avidity functions of anti-rVSVΔG-ZEBOV-GP by day 365; were assessed in serum. (PACTR202005733552021) FINDINGS: In the rVSVΔG-ZEBOV-GP group, 70% and 7% of children had >0 copies/ml of rVSVΔG respectively in plasma by day 3 and in saliva by day 14 after vaccination, with no detection on day 28. Significantly higher but transient AEs occurred in the rVSVΔG-ZEBOV-GP group. Both vaccines induced seroconversion on day 28 and sustainable IgG antibody titres by day 365. Avidity and neutralisation functions of the anti-rVSVΔG-ZEBOV-GP antibodies peaked at day 28 and were maintained by day 365. The replication and shedding do not affect the favourable risk-benefit balance of the rVSVΔG-ZEBOV-GP in children.

Impact of Pre-Existing Immunity and Age on Antibody Responses to Live Attenuated Influenza Vaccine.

Live attenuated influenza vaccines (LAIV) typically induce a poor hemagglutination inhibition (HI) response, which is the standard correlate of protection for inactivated influenza vaccines. The significance of the HI response is complicated because the LAIV vaccine primarily induces the local mucosal immune system, while the HI assay measures the circulating serum antibody response. However, age and pre-existing immunity have been identified as important factors affecting LAIV immunogenicity. This study aimed to extend our understanding of LAIV-induced immunity, particularly, the impact age and pre-existing immunity have on eliciting functional and neutralising antibody responses in paediatric and adult populations vaccinated with LAIV. Thirty-one children and 26 adults were immunized with the trivalent LAIV during the 2013-2014 influenza season in Norway. Children under 9 years received a second dose of LAIV 28 days after the first dose. Blood samples were collected pre- and post-vaccination. HI, microneutralization (MN) and enzyme-linked lectin assay for neuraminidase (NA) antibodies were measured against the vaccine strains. IgG antibody avidity against hemagglutinin (HA) and NA proteins from the vaccine strains was also assessed. Significant correlations were observed between HI and MN responses to A/California/7/2009 (A/H1N1)pdm09-like strain and B/Massachusetts/2/2012-like strain, suggesting that MN is a potential immunological correlate for LAIV. However, the relationship between recipient age (or priming status) and serological response varied between vaccine strains. There was a notable increase in HI and MN responses in all cohorts except naive children against the H1N1 strain, where most recipients had responses below the protective antibody threshold. NAI responses were generally weak in naive children against all vaccine strains compared with adults or antigen-primed children. Post-vaccination antibody avidity increased only in primed children below nine years of age against the A/H1N1 strain. Overall, our findings indicate that LAIV elicits functional and neutralizing antibody responses in both naive and antigen experienced cohorts, however, the magnitude and kinetics of the response varies between vaccine strains.

Sustained immunological memory to SARS-CoV-2 antigens. Three years of observation

The COVID-19 pandemic has ended, but SARS-CoV-2 continues to actively circulate and mutate in the human population. In this regard, it is important to understand for how long post-infectious and post-vaccination immunity may last and how effectively established immunity could act against new mutant SARS-CoV-2 strains. The aim was to study humoral and cellular immunity in a group of COVID-19 convalescent subjects within 3 years after the primary infection. The longitudinal study included 38 adults aged 23–72 years with PCR-confirmed mild or moderate COVID-19 in the second half of 2020. Within three-year follow-up after the onset, the subjects were examined every 6 months for the level of humoral and cellular immunity against SARS-CoV-2 antigens. The parameters of humoral immunity were assessed by enzyme immunoassay using “SARS-CoV-2-IgG quantitative-ELISA-BEST” kits (Vector-Best JSC, Novosibirsk, Russian Federation) for S-protein and “N-CoV-2-IgG PS” (Saint-Petersburg Pasteur Institute, St. Petersburg, Russian Federation) specific to the N-protein. Cellular anti-SARS-CoV-2 immunity was analyzed by evaluating surface CD107a expression on CD8high lymphocytes stimulated with the SARS-CoV-2 S- or N-antigens. It was shown that the dynamics of antibody levels against SARS-COV-2 antigens depends on antigen (S- or N-protein) type, antibody class (IgG or IgA) as well as individual contact history with new SARS-CoV-2 strains. The dynamics of cytotoxic CD8highCD107a+ lymphocyte percentage is moderately positively correlated with that of the corresponding anti-S or N antibody levels. At the same time, change in the levels of both humoral and T-cell responses to SARS-CoV-2 S- or N-protein antigens are weakly negatively correlated with each other. A strong positive correlation was found between changes in the anti-S IgG antibody level and avidity. Avoiding the anti-S IgG neutralization due to frequent mutations of new SARS-CoV-2 strains leads to induced new primary immune responses against SARS-CoV-2 antigens along with the activation of existing responses formed to previous coronavirus strains. The study of immune responses against SARS-CoV-2 antigens allows to predict the persistence of high SARS-CoV-2 anti-S antibody and T-cell response levels.

Changes in the avids of IgG antibodies to the S protein of SARS-CoV-2 after coronavirus infection in medical workers of a temporary infections hospital

BACKGROUND: The effector capabilities of humoral immunity are determined not only by the amount of specific antibodies produced in response to an antigenic effect, but also by their qualitative characteristics, which include avidity ― the total strength of binding to the antigen, which determines the duration and effectiveness of post-infectious immunity to SARS-CoV-2.
 AIM: Is a selective study of the quantity and avidity of IgG antibodies to SARS-CoV-2 over time among medical workers of a temporary infectious diseases hospital in Kazan ― convalescents of COVID-19, during the period from July 2020 to July 2021.
 MATERIALS AND METHODS: Determination of IgG to the S antigen of SARS-CoV-2 by ELISA was carried out using the test system SARS-CoV-2-IgG quantitative-ELISA-BEST (Vector-Best, Russia) and expressed in BAU/ml (binding antibody units). Antibody avidity was determined using a 4.0 M urea solution and expressed as avidity indices. 1, 4 and 7 months after COVID-19 asymptomatic (n=34); mild severity (n=42); moderate severity (n=29); reinfected (n=34). When statistically processing the data, descriptive statistics methods and the Wilcoxon matched data test were used. Differences were considered significant at p 0.05.
 RESULTS: IgG avidity to SARS-CoV-2 depended on the severity of COVID-19. The highest rates of avidity indices were found in the group of those who had a moderate form of COVID-19. If in mild and asymptomatic forms there was a parallel decrease in avidity indices and IgG titer, then in moderate forms an increase in antibody titer was accompanied by a decrease in their avidity 4 months after the infection. 7 months after seroconversion, the IgG level decreased almost twofold, both in mild, asymptomatic and moderate forms. In the group of medical workers who had COVID-19 repeatedly, the initially low levels of avidity indices and antibody titers increased in parallel, while avidity indices after 7 months did not decrease, but remained high. Differences in avidity indices determined the subsequent formation of different trends in the development of the humoral immune response, which were mainly characterized by an uneven decrease in IgG and persistence of IgM antibodies for more than 1 month.
 CONCLUSIONS: The research results expand the understanding of the mechanisms of formation of the humoral immune response and the avidity of IgG antibodies against SARS-CoV-2 in the risk group ― medical workers. The level of humoral immunity decreases in the first six months and varies depending on the severity of COVID-19. The data obtained can be used to identify categories of increased risk of SARS-CoV-2 infection among healthcare workers, make decisions about immunorehabilitation and revaccination against COVID-19.

Antigenic markers of T. gondii for chronic forms of toxoplasmosis in fertility age women

Objective: This study aimed to assess the avidity of IgG antibodies against Toxoplasma gondii in fertile-aged women with a history of abortion. Using the recomLine Toxoplasma IgG Avidity kit, the research investigated the relationship between antibody avidity, T. gondii antigens (GRA1 and SAG1), and the number of abortions to enhance understanding of infection dynamics in this population.
 Methods : Forty (40)fertile aged women (18-37years) with history of abortion and had positive results of IgG Abs by minividus form October 2021 to April 2022 ,Kit of recomLine Toxoplasma IgG Avidity form Mikrogen /Germany,item No.11010, was used ,which is a qualitative in vitro test for the determination the avidity of IgG antibodies against Toxoplasma gondii in human serum or plasma.
 Results: Phase II of toxoplasmosis was positive of antibodies against different antigens detected by recomLine assay, no other significant relation was observed. Also, that there was no significant relation between the period of infection and avidity of IgG –Abs against different antigens of T.gondii detected by recomLine test. In addition The results showed that there was a significant relation between of the number of abortions to GRA1-antigen (P=0.012) and SAG1-antigen (P=0.003) .
 Conclusion: There was a significant relation between of the number of abortions to GRA1 and SAG1-antigens detected by recomLine assay ,where increase in the positive results with the increase in the number of abortions.

The Differences in the Binding of IgM and IgG Antibodies with Erythrocytes and Epithelial Cells

Background:: The studies of agglutinating and adsorbing abilities of IgM and IgG antibodies towards the red blood cells (RBCs) and tissue cells are scarce. background: The studies of agglutinating and adsorbing abilities of IgM and IgG antibodies towards the red blood cells (RBCs) and tissue cells are scarce. Objectives:: The study aimed to estimate the differences in the avidity of blood group-specific IgM and IgG antibodies to RBCs and epithelial cells. Methods:: The reaction of hemagglutination, adsorption, mixed agglutination reaction and saliva inhibition test were used. Anti-B 2-54 monoclonal antibody, polyclonal citrated plasma and the heated plasma were used for investigation of IgM and IgG antibodies. Results:: IgM antibodies showed high adsorbing ability to RBCs and epithelial cells in an alkaline medium. On the contrary, the heated plasma containing IgG antibodies showed high adsorbing ability to RBCs and epithelial cells in the acid medium as compared to the alkaline medium. Complete adsorption of IgG antibodies was observed by epithelial cells as compared to erythrocytes. A mixed agglutination reaction confirmed the strong binding of anti-B IgG antibodies with group B epithelial cells in an acid medium. Conclusion:: The binding of polyclonal IgM and IgG group-specific antibodies with red blood cells and epithelial cells depends on the opposite values of pH of the medium. IgG antibodies completely adsorb on epithelial cells contrary to IgM antibodies. Highlights:: Blood group-specific IgG antibodies showed high avidity to epithelial cells as compared to red blood cells. IgG antibodies demonstrated high agglutinating ability in alkaline medium and strong adsorbing ability in acid medium contrary to IgM antibodies, demonstrating high adsorption properties in alkaline medium.

Fasciola hepatica infection modifies IgG1 specific immune response to foot-and-mouth disease virus induced by vaccination

Fasciola hepatica, a worldwide distributed helminth, has a robust immunoregulatory effect in the host, increasing the susceptibility to secondary infections. Foot and mouth disease (FMD) is a highly contagious acute vesicular viral disease effectively controlled by vaccination in endemic regions. Despite the evidence of immunoregulatory effects, the impact of fasciolosis on the immune response induced by FMD vaccination in cattle has never been assessed. Our objective was to evaluate whether the infection by F. hepatica in cattle influences the long-term immunity elicited by the currently used commercial FMD-inactivated vaccines. Aberdeen Angus steers negative for F. hepatica were vaccinated twice against FMD virus (FMDV) during the first 6 months of age using a commercial oil vaccine formulated with A24/Cruzeiro and O1/Campos strains. When maternal antibodies against F. hepatica were weaned (18––20 months of age) animals were divided into groups of 12 and infected or mock-infected with 500 metacercariae/animal. Individual serum samples were collected at 0-, 28-, 59-, 87- and 157-days post-infection (dpi). Indirect ELISAs were used to detect A24/Cruzeiro specific bovine IgG and IgG subtypes. The total IgG antibody levels and avidity against FMDV did not show significant differences between all the groups. The commercial vaccine induced higher IgG2 than IgG1 titers in vaccinated animals. Anti-FMDV IgG1 levels significantly decreased in the infected group at 28 dpi. In addition, the avidity of IgG1 FMDV-specific antibodies at day 28 in the infected group was reduced compared to the control. These results show that F. hepatica infection modified anamnestic responses against FMDV, reducing serum IgG1 titers and avidity. To our knowledge, this is the first report of immune-regulation of F. hepatica altering the immune response of FMD vaccines, one of the most globally used animal vaccines.

Neutralizing Antibody Response to Genotypically Diverse Measles Viruses in Clinically Suspected Measles Cases.

The neutralizing antibody (Nt-Ab) response to vaccine and wild-type measles viruses (MeV) was studied in suspected measles cases reported during the years 2012-2016. The neutralization activity against MeV A, D4 and D8 genotypes was studied on sera (Panel A; n = 68 (measles-immunized) and Panel B; n = 50 (unvaccinated)) that were either laboratory confirmed or not confirmed by the presence of IgM antibodies. Additionally, the Nt-Ab response in Panel A was measured against the MeV vaccine and four wild-type viruses. Neutralization results were compared using homology modeling and molecular dynamics simulation (MDS) of MeV-hemagglutinin (H) and fusion (F) proteins. Overall, the Nt-Ab titres for MeV-A were found to be significantly lower than MeV-D4 and MeV-D8 viruses for Panel A. No major difference was noted in Nt-Ab titres between MeV-D8 viruses (Jamnagar and New Delhi), whereas MeV-D4 (Sindhudurg and Bagalkot (BGK) viruses) showed significant differences between Nt-Ab titres for Panel B. Interestingly, the substitutions observed in epitopes of H-protein, L249P and G316A are observed to be unique to MeV-BGK. MDS of H-protein revealed significant fluctuations in neutralizing epitopes due to L249P substitution. The majority of the clinically suspected cases showed Nt-Abs to MeV wild-types. Higher IgG antibody avidity and Nt-Ab titres were noted in IgM-negatives than in IgM-positives cases, indicating reinfection or breakthrough. MDS revealed reduced neutralization due to decreased conformational flexibility in the H-epitope.

Antibody responses to recombinant vesicular stomatitis virus-Zaire Ebolavirus vaccination for Ebola virus disease across doses and continents: 5-year durability

ObjectivesTo report 5-year persistence and avidity of antibodies produced by the live-attenuated recombinant vesicular stomatitis virus (rVSV) expressing the Zaire Ebolavirus (ZEBOV) glycoprotein (GP), known as rVSV-ZEBOV (Ervebo®). MethodsHealthy adults vaccinated with 300,000 or 10–50 million plaque-forming units of rVSV-ZEBOV in the WHO-coordinated trials of 2014–2015 were followed for up to 4 (Lambaréné, Gabon) and 5 (Geneva, Switzerland) years. We report seropositivity rates, geometric mean titres (GMTs), and population distribution of ZEBOV-GP ELISA IgG antibodies, neutralizing antibodies (pseudovirus and live-virus neutralization) and antibody avidity; the primary outcome was ZEBOV-GP ELISA IgG GMTs at 4 or 5 years compared with 1 year (Y1) after immunization. ResultsAmong the 168 eligible vaccinees (Geneva: 97 and Lambaréné: 71) enrolled 1 year post-immunization, 146 (87%) remained enrolled at 4 years (Geneva: n = 88, Lambaréné: n = 58), and 84 (87%, Geneva) at 5 years post-vaccination. ZEBOV-GP ELISA IgG GMTs plateaued, with no declining trend from 1 year through the last time point assessed (1147.8 [95% CI 874.3–1507.0] at Y1 versus 1548.1 [95% CI 1136.6–2108.5] at Y5 in Geneva volunteers receiving ≥10 million plaque-forming units of rVSV-ZEBOV), their avidity matching that of ZEBOV convalescents. Live-virus neutralizing antibodies were detected for shorter periods and in fewer vaccinees (53/95 [56%] at Y1 versus 35/84 [42%] at Y5 in Geneva volunteers, all dose levels). DiscussionTitres at Y1 emerged as a correlate of antibody persistence at Y5. The findings of persistent ZEBOV-GP ELISA IgG titres yet shorter-lasting, lower titres of live-virus neutralizing antibodies suggest the contribution of antibody-mediated protective mechanisms other than neutralization. Long-term clinical efficacy of rVSV-ZEBOV, however, requires further study.

The quantity and quality of anti-SARS-CoV-2 antibodies show contrariwise association with COVID-19 severity: lessons learned from IgG avidity.

Gaining more appreciation on the protective/damaging aspects of anti-SARS-CoV-2 immunity associated with disease severity is of great importance. This study aimed to evaluate the avidity of serum IgG antibodies against SARS-CoV-2 spike (S) and nucleocapsid (N) in hospitalized symptomatic COVID-19 patients and asymptomatic RT-PCR-confirmed SARS-CoV-2 carriers as well as to compare antibody avidities with respect to vaccination status, vaccination dose and reinfection status. Serum levels of anti-S and anti-N IgG were determined using specific ELISA kits. Antibody avidity was determined by urea dissociation assay and expressed as avidity index (AI) value. Despite higher IgG levels in the symptomatic group, AI values of both anti-S and anti-N IgG were significantly lower in this group compared to asymptomatic individuals. In both groups, anti-S AI values were elevated in one-dose and two-dose vaccinees versus unvaccinated subjects, although significant differences were only detected in the symptomatic group. However, anti-N avidity showed no significant difference between the vaccinated and unvaccinated subgroups. Almost all vaccinated patients of different subgroups (based on vaccine type) had higher anti-S IgG avidity, while the statistical significance was detected only between those receiving Sinopharm compared to the unvaccinated subgroup. Also, statistically significant differences in antibody AIs were only found between primarily infected individuals of the two groups. Our findings indicate a key role for anti-SARS-CoV-2 IgG avidity in protection from symptomatic COVID-19 and calls for the incorporation of antibody avidity measurement into the current diagnostic tests to predict effective immunity toward SARS-CoV-2 infection or even for prognostic purposes.

Integrated immune monitoring of HCMV infection in pregnant women with complications and its association with adverse pregnancy outcomes

Human Cytomegalovirus (HCMV) infection is associated with bad obstetric history (BOH) and adverse pregnancy outcomes (APO). Here, we characterized antiviral humoral profiles, systemic and virus specific cellular immune responses concurrently in pregnant women (n = 67) with complications including BOH and associated these signatures with pregnancy outcomes. Infection status was determined using nested blood PCR, seropositivity and IgG avidity by ELISA. Systemic and HCMV specific (pp65) cellular immune responses were evaluated by flow cytometry. Seropositivity was determined for other TORCH pathogens (n = 33) on samples with recorded pregnancy outcomes. This approach was more sensitive in detecting HCMV infection. Blood PCR positive participants, irrespective of their IgG avidity status, had higher cytotoxic potential in circulating CD8+ T cells (p < 0.05) suggesting that infection associated cellular dysfunction was uncoupled with avidity maturation of antiviral humoral responses. Also, impaired anamnestic degranulation of HCMV-pp65-specific T cells compared to HCMV blood PCR negative participants (p < 0.05) was observed. APO correlated with HCMV blood PCR positivity but not serostatus (p = 0.0039). Most HCMV IgM positive participants (5/6) were HCMV blood PCR positive with APO. None were found to be IgM positive for other TORCH pathogens. Multiple TORCH seropositivity however was significantly enriched in the APO group (p = 0.024). Generation of HCMV specific high avidity IgG antibodies had no bearing on APO (p = 0.9999). Our study highlights the utility of an integrated screening approach for antenatal HCMV infection in the context of BOH, where infection is associated with systemic and virus specific cellular immune dysfunction as well as APO.

Dynamics in maturation of SARS-CoV-2 RBD-specific IgG antibody avidity depending on immunization timeframe and type

The aim is to examine dynamics of avidity maturation of IgG antibodies against SARS-CoV-2 RBD depending on the type of immunization (vaccination or infection), as well as on the duration and frequency of immunization. Materials and methods. The study was performed on two sample cohorts collected at two time points during COVID-19 pandemic. The first cohort (group No. 1) consisted of 87 samples of blood sera obtained from COVID-19 convalescents in the period from March to September 2020. The second cohort included 204 samples obtained in September 2021 from two patient groups. Group No. 2 (n = 64) patients immunized with a full course of Gam-Covid-Vac, group No. 3 (n = 140) COVID-19 convalescent patients and subjects vaccinated with Gam-Covid-Vac (hybrid immunity). Results and conclusion. The dynamics of avidity maturation for SARS-CoV-2 RBD IgG antibodies depending on the method and frequency of immunization, showed that the most effective immunity was formed in COVID-19 convalescent patients and subjects vaccinated with a full course of Gam-Covid-Vac. The hybrid immunity showed not only a significantly higher (compared with groups No. 1 and No. 2) level of IgG antibodies (median 228 BAU/ml vs 75 or 119 BAU/ml, p 0.001), but also a higher level of avidity (IA 90.5% vs 54.5 and 76.6, respectively, p 0.001, 4M urea). In the test for assessing the avidity index with the denaturing agent 8M urea in patients with hybrid immunity, the median level of IA was 25% versus 14.8% and 16% in COVID-19 convalescents and vaccinated subjects (p 0.001), only in 8 patients IA was higher than 50%. While comparing a single infection of COVID-19 with a full course of Gam-Covid-Vac, it was shown that vaccination leads to higher IgG levels (median values in groups 119 and 75 BAU/ml, p 0.001) and to a higher avidity index (median 76.6% vs 54.5%). Thus, the more rapid induction of high-avidity antibodies was in vaccinated individuals at early stages of immunization (up to 4 months), during the period when IgG avidity maturation has not yet been completed. Our results showed that during this period vaccination leads to production of antibodies with avidity index at median level of 82% versus 36% in COVID-19 convalescents at similar time point.

RBD and Spike DNA-Based Immunization in Rabbits Elicited IgG Avidity Maturation and High Neutralizing Antibody Responses against SARS-CoV-2.

Neutralizing antibodies (nAbs) are a critical part of coronavirus disease 2019 (COVID-19) research as they are used to gain insight into the immune response to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infections. Among the technologies available for generating nAbs, DNA-based immunization methods are an alternative to conventional protocols. In this pilot study, we investigated whether DNA-based immunization by needle injection in rabbits was a viable approach to produce a functional antibody response. We demonstrated that three doses of DNA plasmid carrying the gene encoding the full-length spike protein (S) or the receptor binding domain (RBD) of SARS-CoV-2 induced a time-dependent increase in IgG antibody avidity maturation. Moreover, the IgG antibodies displayed high cross neutralization by live SARS-CoV-2 and pseudoviruses neutralization assays. Thus, we established a simple, low cost and feasible DNA-based immunization protocol in rabbits that elicited high IgG avidity maturation and nAbs production against SARS-CoV-2, highlighting the importance of DNA-based platforms for developing new immunization strategies against SARS-CoV-2 and future emerging epidemics.

Antibody avidity to pertussis toxin after acellular pertussis vaccination and infection

ABSTRACT Pertussis toxin (PT) is a unique virulence factor of Bordetella pertussis, and therefore a key component of acellular pertussis vaccines. Although immunity after infection seems to persist longer than after vaccination, the exact mechanisms are not fully known. In this study the overall binding strength (avidity) of anti-PT IgG antibodies was compared after acellular booster vaccination and infection, as a parameter to evaluate long-lasting protection. Danish and Finnish serum samples from a total of 134 serologically confirmed patients and 112 children who received acellular booster vaccines were included in this study. The concentration of anti-PT IgG was first determined by ELISA, followed by two separate ELISAs to evaluate antibody avidity: either with a dilution series of urea as a bond-breaking agent of antibody and antigen binding and a constant anti-PT IgG concentration between the samples or with a constant dilution ratio of sera and detergent. In addition to urea, the use of diethylamine and ammonium thiocyanate as disruptive agents were first compared between each other. A strong Spearman correlation (R > 0.801) was noted between avidity and concentration of anti-PT IgG antibodies if a constant serum dilution method was used, and avidity was noted to be higher in patients in comparison to vaccinees in Denmark, but not in Finland. However, no correlation between antibody concentration and avidity was found if a constant anti-PT IgG concentration was used (R = −0.157). With this method, avidity after vaccination was significantly higher in comparison to that after infection in both Danish and Finnish subjects (p < 0.01). A shorter time since the latest booster vaccination was found to affect avidity positively on the next PT-antigen exposure with either vaccination or infection.

Новые подходы к ведению пациентов с нестойкой ремиссией круглогодичного аллергического ринита на фоне персистирующей хламидийной инфекции

Currently, allergic rhinitis is a global socioeconomic problem. According to current statistics, from 15 to 30% of the world’s population suffers from year-round or seasonal allergic rhinitis. Increasingly, the attention of Russian clinicians is attracted by the problem of year-round allergic rhinitis as there is an increase in the incidence in patients of the central zone of the Russian Federation with this form of rhinitis due to sensitization to house dust mite allergens, epidermal allergens of domestic animals, insect and mold allergens. Despite a timely diagnosis and received basic treatment, patients suffering from year-round allergic rhinitis often fail to achieve stable remission. Therefore, we can conclude that a more thorough diagnosis of the disease is needed, aimed at identifying other factors that affect the course of the disease. Objective. To develop a scheme for diagnosing a possible persistent respiratory chlamydial infection that affects the course of year-round allergic rhinitis in patients with a tendency to transient remissions. Materials and methods. Computed tomography of the paranasal sinuses, nasal swab for flora, PCR scraping of the nasal mucosa for the detection of Epstein–Barr virus (EBV) DNA, determination of viral DNA of cytomegalovirus infection (CMV) (PCR scraping of the nasal mucosa), determination of DNA in the scraping of epithelial cells of the nasal mucosa (PCR scraping) of human herpes virus type 6 (HHV-6 type). Patients who had pathological changes in computed tomography of the paranasal sinuses, deviations from the normal flora during bacteriological culture, and positive results in the PCR study of the above infections were excluded from the study. Then, PCR scraping of the nasopharyngeal mucosa for the detection of chlamydia pneumoniae, a survey of complaints (SNOT-22 questionnaire), data from an objective examination method (examination of ENT organs using video endoscopic technologies), an immunological examination of blood serum for IgG antibodies to chlamydial infection, further avidity of IgG antibodies to chlamydia pneumoniae and serum IL-6. Conclusion. The proposed diagnostic scheme will allow identifying a possible persistent respiratory chlamydial infection, which is the cause of transient remission of year-round allergic rhinitis, and developing a new integrated approach to the management of patients with year-round allergic rhinitis associated with this infection.

Rubella virus IgM and IgG antibodies with avidity in pregnant women and outcomes at a tertiary facility in Ghana.

Congenital rubella syndrome (CRS) is a recognised cause of childhood deafness and blindness caused by the transplacental transmission of rubella virus during pregnancy. Women in the reproductive age group, and by extension their unborn babies may therefore be at increased risk. The prevalence of Rubella virus specific IgM and IgG antibodies, including IgG avidity, was determined in pregnant women attending the antenatal clinic at a Teaching Hospital in Ghana. One hundred and forty-five women in their second and third trimesters of pregnancy from the outpatient clinic were recruited over a period of 2 months after written informed consent was obtained. Study participants completed a questionnaire and venous blood drawn for IgM, IgG, and avidity testing using SERION ELISA (SERION® Immunologics, Würzburg, Germany). Babies of mothers with positive or indeterminate IgM and low avidity IgG antibodies were offered specialist cardiological, ophthalmological or hearing assessment during follow up. One hundred and twenty-eight (88.3%) had only IgG antibodies, 5 (3.4%) had IgM and IgG antibodies, while 12 (8.3%) had no antibodies. No patient had IgM antibodies alone. Ten women (6.9%) had indeterminate levels of IgM antibodies. Majority of the women had high avidity IgG antibodies, while 5 (3.4%) had low avidity antibodies. No patient had IgM with low avidity antibodies. There was no statistical association between socio-demographic factors and the presence of IgM, IgG (low or high avidity) antibodies. Of all the children followed, none had the clinical definition of CRS. Consistent with the World Health Organization elimination strategy for measles and rubella viruses, non-immune women in the reproductive age group should be vaccinated. The immunization programme should be expanded to include teenagers and adults. Though Congenital Rubella Syndrome was not detected, the risk still remains.

Verification of a case of mixed infection with Lyme disease, tick-borne encephalitis and COVID-19

Background. The relationship between pathogens of new diseases and tick-borne infections is an underinvestigated direction in the problem of infectious diseases.The aim. To show the features of identifying the markers of Borrelia burgdorferi, tickborne encephalitis and SARS-CoV-2 pathogens on the example of a case of a triple mixed infection (Lyme disease, tick-borne encephalitis and COVID-19) and using comprehensive studies.Methods. In 2019–2021, a comprehensive study of 7 blood samples from a patient with mixed infection was carried out. We used real-time polymerase chain reaction (PCR), enzyme immunoassay (ELISA) and determined antigen, IgM, IgG antibodies, and avidity index (AI) of IgG antibodies.Results. Ixodid tick-borne borreliosis was diagnosed in a patient 5 months after contagion. Only high-avid Lyme-IgG antibodies were detected. Low-avid Lyme- IgG antibodies appeared against the background of a reduced general condition. At the same time, high-avid IgG (cut-off index (COI) – 7.8) and IgM (COI = 1.2) antibodies to the TBE virus were detected. In July 2020, the patient was infected with SARSCoV-2. TBE virus which passed into the body simultaneously with Borrelia in the fall of 2019 was activated. Although the patient did not have specific symptoms of TBE, in subsequent blood samples (No. 4, 5, 6) we found TBEV antigen (optical density (OD) – 4.3; 1.9 and 2.0 respectively) and IgM (COI = 1.3; 0,9 and 0 respectively). These results were recognized as TBEV activation, which contributed to an increase in the avidity of IgG antibodies (AI = 65 %; 100 % and 63 % respectively). IgM antibodies to SARSCoV-2 virus were not detected, as opposed to the high levels of IgG (COI = 8.2; 8.1; 8.4 and 14.7 respectively).Conclusions. Therefore, using not only the common methods of diagnosing (PCR and ELISA), but also the determination of the antibody avidity degree, we have shown that when analyzing a case of a triple mixed infection, B. burgdorferi dominates in the human body and causes a long-term chronic course of the disease.

Congenital Cytomegalovirus Infection and Maternal Primary Cytomegalovirus Infection in Universal Newborn Hearing Screening Referral Patients: A Prospective Cohort Study

Background: There are no detailed reports in the literature on maternal cytomegalovirus antibody screening for universal newborn hearing screening (UNHS) referral patients. We examined maternal cytomegalovirus antibody screening results and estimated the incidence of maternal primary cytomegalovirus infection among UNHS referral patients. Methods: During September 2013–March 2021, fresh urine samples were collected in the first week after birth from 98 neonates with UNHS referral results at 15 obstetrical institutions in Mie, Japan (the first hearing screening). We performed a real-time polymerase chain reaction analysis to detect cytomegalovirus DNA in the samples. Infants with ≥200 copies/mL of cytomegalovirus DNA were diagnosed with congenital cytomegalovirus (cCMV) infection. A second hearing screening was performed, and patients with positive results were sent to the otorhinolaryngologists for further examinations of congenital hearing loss. We calculated incidence rates (%) with 95% confidence intervals (CIs) for cCMV infection among patients with UNHS referral results and maternal primary cytomegalovirus infection among patients who underwent maternal cytomegalovirus antibody screening. Results: Among the 98 neonates with UNHS referral results (the first hearing screening), 5 were diagnosed with cCMV infection (incidence rate: 5.1%; 95% CI: 0.8–9.5). All five patients with cCMV had positive second hearing screening results and were sent to their otorhinolaryngologists. All five were diagnosed with congenital hearing loss, and four were diagnosed with congenital hearing loss secondary to cCMV infection. The remaining patient with cCMV infection was diagnosed with congenital hearing loss unrelated to cCMV infection. Of the 98 patients, 60 underwent maternal cytomegalovirus antibody screening. Among the 60 patients, six had maternal primary cytomegalovirus infection during pregnancy (incidence rate: 10.0%; 95% CI: 2.4–17.6). Of the six patients, four were positive for cytomegalovirus immunoglobulin (CMV Ig) G and IgM antibodies in maternal blood with low CMV IgG antibody avidity results during early pregnancy, while the remaining two had maternal CMV IgG antibody seroconversion during pregnancy. Conclusions: This is the first study to examine the maternal primary cytomegalovirus infection incidence rate in patients with UNHS referral results (the first hearing screening). We identified a 10-fold higher risk in this population (10.0%) than in the general population (0.98%).

Daily preventive zinc supplementation increases the antibody response against pathogenic Escherichia coli in children with zinc insufficiency: a randomised controlled trial

Zinc deficiency impairs the antibody-mediated immune response and is common in children from lower-income countries. This study aimed to investigate the impact of different zinc supplementation regimens (7, 10 or 20 mg/day elemental zinc)—therapeutic dispersible zinc tablets (TZ), daily multiple micronutrient powder (MNP), daily preventive zinc tablets (PZ) and placebo powder (control)—and compare between baseline and endline antibody production against pathogenic Escherichia coli in Laotian children (aged 6–23 months). Fifty representative plasma samples of each treatment group were randomly selected from 512 children to determine anti-E. coli IgG antibody levels and avidity. Of the 200 children, 78.5% had zinc deficiency (plasma zinc concentration < 65 µg/dL) and 40% had anaemia before receiving zinc supplementation. aAfter receiving the TZ, MNP or PZ regimen, the plasma anti-E. coli IgG levels were significantly increased compared with baseline; the effect on the antibody level was more pronounced in children with zinc deficiency. Interestingly, there was increased anti-E. coli IgG avidity in the control and PZ groups. This study suggests that PZ might be the optimal zinc supplementation regimen to increase both the quantity and quality of antibody responses in children with zinc deficiency. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT02428647 (NCT02428647, 29/04/2015).

Antibody Avidity and Neutralizing Response against SARS-CoV-2 Omicron Variant after Infection or Vaccination.

Background The recently emerged SARS-CoV-2 Omicron variant exhibits several mutations on the spike protein, enabling it to escape the immunity elicited by natural infection or vaccines. Avidity is the strength of binding between an antibody and its specific epitope. The SARS-CoV-2 spike protein binds to its cellular receptor with high affinity and is the primary target of neutralizing antibodies. Therefore, protective antibodies should show high avidity. This study aimed at investigating the avidity of receptor-binding domain (RBD) binding antibodies and their neutralizing activity against the Omicron variant in SARS-CoV-2 infected patients and vaccinees. Methods Samples were collected from 42 SARS-CoV-2 infected patients during the first pandemic wave, 50 subjects who received 2 doses of mRNA vaccine before the Omicron wave, 44 subjects who received 3 doses of mRNA vaccine, and 35 subjects who received heterologous vaccination (2 doses of adenovirus-based vaccine plus mRNA vaccine) during the Omicron wave. Samples were tested for the avidity of RBD-binding IgG and neutralizing antibodies against the wild-type SARS-CoV-2 virus and the Omicron variant. Results In patients, RBD-binding IgG titers against the wild-type virus increased with time, but remained low. High neutralizing titers against the wild-type virus were not matched by high avidity or neutralizing activity against the Omicron variant. Vaccinees showed higher avidity than patients. Two vaccine doses elicited the production of neutralizing antibodies, but low avidity for the wild-type virus; antibody levels against the Omicron variant were even lower. Conversely, 3 doses of vaccine elicited high avidity and high neutralizing antibodies against both the wild-type virus and the Omicron variant. Conclusions Repeated vaccination increases antibody avidity against the spike protein of the Omicron variant, suggesting that antibodies with high avidity and high neutralizing potential increase cross-protection against variants that carry several mutations on the RBD.