Protective Antibody Levels Research Articles

Immunogenicity and safety of vaccination in children with paediatric rheumatic diseases: a scoping review

Children with paediatric rheumatic diseases (PRDs) are at increased risk of vaccine-preventable disease. Safe and effective vaccination is central to preventive care in PRD patients; however, uncertainty surrounding immunogenicity and safety has contributed to suboptimal vaccination. The aim of this study was to evaluate treatment effect on immunogenicity to vaccination in PRD patients and assess vaccine safety, specifically adverse events following immunisation (AEFI) and disease flare. Scoping review. In this scoping review, a systematic search of PubMed, CINAHL and Embase databases was conducted from 2014 to 23 August 2022 to identify observational studies evaluating the immunogenicity and safety of commonly used vaccinations in PRD patients. The primary outcome was immunogenicity (defined as seroprotection and protective antibody concentrations), with secondary outcomes describing AEFI and disease flare also extracted. Due to extensive heterogeneity related to diagnostic and vaccination variability, narrative synthesis was used to describe the findings of each study. Study quality was assessed via the Mixed Methods Appraisal Tool. The review was prospectively registered with PROSPERO (CRD42022307212). The search yielded 19 studies evaluating immunogenicity to vaccination and incidence of AEFI and disease flares in this population, which were of acceptable quality. Corticosteroids did not have deleterious effects on vaccine response. Treatment with conventional disease-modifying antirheumatic drugs (DMARDs) and biologic DMARDs generally had no effect immunogenicity in PRD patients. While patients exhibited adequate seroprotection, protective antibody levels were lower in patients on some immunosuppressant agents. Varicella infections were recorded post vaccination in several patients with low protective antibody levels undergoing treatment with DMARDs and corticosteroids. Most vaccines appear safe and effective in PRD patients, despite immunosuppressant treatment. Booster vaccinations should be considered with some studies highlighting inadequate seroprotection following primary course of vaccinations with acceleration of antibody decline over time. There was limited evidence to support avoiding live vaccines in PRD patients.

Comparison of humoral immune response in heterologous and homologous COVID-19 booster vaccine groups using CoronaVac and mRNA-based BNT162b2 vaccines.

Heterologous COVID-19 booster vaccination is an alternative strategy to homologous vaccination, especially in developing countries, due to shortages, delays, or unequal distribution of COVID-19 vaccines. We compared cohorts vaccinated with different vaccine combinations to investigate whether a heterologous booster dose of mRNA-based BNT162b2 vaccine boosts the immune response in individuals primed with the CoronaVac vaccine. Anti-RBD IgG is generally measured 4 weeks after primary immunization and 4 weeks after booster vaccination. Data on anti-receptor-binding domain (anti-RBD) IgG antibody titers and clinical characteristics were provided by infection control units. The highest median anti-RBD IgG antibody titers (14589 AU/mL) after primary immunization was observed in the group vaccinated with two doses of BNT162b2 vaccine. Antibody titers were lower 4 months or more after the second CoronaVac vaccine dose in CoronaVac recipients with or without previous COVID-19. In the homologous COVID-19 booster vaccine group (primed with two doses of CoronaVac 4 weeks apart and a single booster dose of CoronaVac) the median anti-RBD titers decreased from 1025 to 242 AU/mL before the booster dose. In the heterologous group (primed with two doses of CoronaVac 4 weeks apart and a single booster dose of BNT162b2), the median anti-RBD titer increased to 31624 AU/mL, a 132-fold increase, 16 days after the booster dose. After the second dose of CoronaVac, protective neutralizing antibody levels decrease over time, and a booster dose is required. Heterologous COVID-19 booster vaccination with BNT162b2 is effective at boosting neutralizing antibody levels.

Soroprevalência de anticorpos contra o vírus da cinomose canina, parvovírus e adenovírus em cães de um abrigo de animais brasileiro

ABSTRACT This study aimed to identify and compare the seroprevalence for canine distemper virus (CDV), canine parvovirus (CPV), and canine adenovirus (CAV) between newly admitted and already sheltered dogs. 122 dogs over six months of age and unvaccinated upon admission were sampled and divided into two groups: (A) newly admitted dogs and (B) dogs sheltered for at least two months. Sera were collected to determine IgG antibody titers against CDV, CPV, and CAV. We conducted a descriptive analysis of the samples and a chi-square test to investigate the relationship between potential elements associated with protective antibody titers. The results were: 56.5% of the dogs had protective levels of antibodies to all three pathogens. Dogs in group A had lower titers compared to those in group B for all three pathogens, with significant differences for CDV and CAV. We found no significant difference between the proportion of seropositive dogs and their age or reproductive status. The study suggests that the examined pathogens can circulate in the animal shelter and that dogs can be more exposed to these pathogens in the shelter than in the urban environment. Therefore, an effective immunization program should be carried out on all animals upon admission to shelters.

Vaccine Responses in Congenital Cytomegalovirus Infection.

There is limited information on vaccine responses in children with congenital cytomegalovirus infection (cCMV). We studied diphtheria, tetanus, measles, mumps and rubella vaccine responses in 6-year-old children with cCMV and controls. Protective antibody levels and geometric mean concentrations did not differ significantly between the study groups. Therefore, immunizations for children with cCMV should be administrated according to established national schedules.

Şap hastalığı (FMD) ve üç gün hastalıklarına (BEF) karşı eş zamanlı aşılanmış sığırlarda bağışıklık yanıt

Bovine ephemeral fever (BEF) virus is an arthropod-borne rhabdovirus and causing an acute febrile illness disease in cattle and water buffalo. Foot-and-mouth disease (FMD) is a highly infectious viral disease of mammals and has a great potential for causing severe economic loss in susceptible cloven-hoofed animals. FMD and BEF vaccines are widely used in countries where both diseases are seen together. This study was carried out to determine the immunological response of cattle simultaneously vaccinated with BEF and FMD vaccines. For this purpose, the cattle were divided into 4 groups in this study as single FMD vaccination group (Group 1; n=10), single BEF vaccination group (Group 2; n=10), BEF+FMD simultaneously vaccinated group (Group 3; n=10) and unvaccinated control group (Group 4; n=10). After the first vaccinations, booster BEF vaccine was applied to the cattle in groups 2 and 3. Although there was no increase in the neutralizing antibody titers against BEF and FMD virus in the blood serums of unvaccinated cattle on the 30th and 60th days of vaccination, There were significant increases in statistically protective neutralizing antibody levels in the vaccinated cattle. As a result, it was demonstrated with this study that BEF and FMD vaccines can be applied simultaneously to combat both diseases in cattle.

Stabilized recombinant SARS-CoV-2 spike antigen enhances vaccine immunogenicity and protective capacity.

The SARS-CoV-2 spike (S) glycoprotein is synthesized as a large precursor protein and must be activated by proteolytic cleavage into S1 and S2. A recombinant modified vaccinia virus Ankara (MVA) expressing native, full-length S protein (MVA-SARS-2-S) is currently under investigation as a candidate vaccine in phase I clinical studies. Initial results from immunogenicity monitoring revealed induction of S-specific antibodies binding to S2, but low-level antibody responses to the S1 domain. Follow-up investigations of native S antigen synthesis in MVA-SARS-2-S-infected cells revealed limited levels of S1 protein on the cell surface. In contrast, we found superior S1 cell surface presentation upon infection with a recombinant MVA expressing a stabilized version of SARS-CoV-2 S protein with an inactivated S1/S2 cleavage site and K986P and V987P mutations (MVA-SARS-2-ST). When comparing immunogenicity of MVA vector vaccines, mice vaccinated with MVA-SARS-2-ST mounted substantial levels of broadly reactive anti-S antibodies that effectively neutralized different SARS-CoV-2 variants. Importantly, intramuscular MVA-SARS-2-ST immunization of hamsters and mice resulted in potent immune responses upon challenge infection and protected from disease and severe lung pathology. Our results suggest that MVA-SARS-2-ST represents an improved clinical candidate vaccine and that the presence of plasma membrane-bound S1 is highly beneficial to induce protective antibody levels.

A genetically engineered, stem-cell-derived cellular vaccine

Despite rapid clinical translation of COVID-19 vaccines in response to the global pandemic, an opportunity remains for vaccine technology innovation to address current limitations and meet challenges of inevitable future pandemics. We describe a universal vaccine cell (UVC) genetically engineered to mimic natural physiological immunity induced upon viral infection of host cells. Cells engineered to express the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike as a representative viral antigen induce robust neutralizing antibodies in immunized non-human primates. Similar titers generated in this established non-human primate (NHP) model have translated into protective human neutralizing antibody levels in SARS-CoV-2-vaccinated individuals. Animals vaccinated with ancestral spike antigens and subsequently challenged with SARS-CoV-2 Delta variant in a heterologous challenge have an approximately 3 log decrease in viral subgenomic RNA in the lungs. This cellular vaccine is designed as a scalable cell line with a modular poly-antigenic payload, allowing for rapid, large-scale clinical manufacturing and use in an evolving viral variant environment.

Features of course of chickenpox and immunization of children with congenital epidermolysis bullosa from <i>Varicella zoster virus</i>: Results of retrospective and prospective study

Patients with congenital epidermolysis bullosa (CEB) are at increased risk of developing skin infections. In this category of patients, infection with the varicella zoster virus (VZV) can lead to such complications.Purpose of the study. To assess the severity of Varicella (VA) and the immune status of patients with CEB who had a history of VA. To study the efficacy and safety of the varicella vaccine in patients with CEB.Methods. During the study, two groups were formed: children with CEB who had a history of VO (group 1), children who received one dose of vaccine against VO (group 2). The severity of chickenpox in children from group 1 was assessed based on the survey data. The immune status of participants in groups 1 and 2 was determined by the level of serum IgG antibodies to VZV by enzyme immunoassay. The safety of immunization against varicella in children with CEB was assessed by the number of adverse events in the post-vaccination period.Results. The study included 16 children with CEB who had a history of chickenpox and 30 children with CEB who were vaccinated against chickenpox. According to the survey, in group 1 5 (31.25%) people had mild chickenpox, 8 (50.00%) children had moderate severity, and 3 (18.75%) children had a severe course of the disease. According to the results of laboratory data, in 15 (94.00%) children, a sufficient level of protective antibodies was formed after the disease. Thirty patients were immunized with the first dose of varicella vaccine. The vast majority of patients developed a level of protective antibodies to the varicella-zoster virus. All patients did not have serious adverse events and worsening of the underlying disease in the post-vaccination period.Conclusion. The data obtained indicate a good safety profile and efficacy of the first dose of the varicella vaccine and allow us to proceed with further observations after the completion of the course of immunization of children with CEB against this infection.

SARS-CoV-2 Anti-Spike IgG Antibody and ACE2 Receptor Binding Inhibition Levels among Breakthrough Stage Veteran Patients.

SARS-CoV-2 mRNA vaccines have been critical to curbing pandemic COVID-19; however, a major shortcoming has been the inability to assess levels of protection after vaccination. This study assessed serologic status of breakthrough infections in vaccinated patients at a Veterans Administration medical center from June through December 2021 during a SARS-CoV-2 delta variant wave. Breakthrough occurred mostly beyond 150 days after two-dose vaccination with a mean of 239 days. Anti-SARS-CoV-2 spike (S) IgG levels were low at 0 to 2 days postsymptoms but increased in subjects presenting thereafter. Population measurements of anti-S IgG and angiotensin converting enzyme-2 receptor (ACE2-R) binding inhibition among uninfected, vaccinated patients suggested immune decay occurred after 150 days with 62% having anti-S IgG levels at or below 1,000 AU comparable with breakthrough patients at 0 to 2 days postsymptom onset. In contrast, vaccination after resolved infection conferred robust enduring anti-S IgG levels (5,000 to >50,000 AU) with >90% ACE2-R binding inhibition. However, monoclonal antibody (MAb)-treated patients did not benefit from their prior infection suggesting impaired establishment of B cell memory. Analysis of boosted patients confirmed the benefit of a third vaccine dose with most having anti-S IgG levels above 5,000 AU with >90% ACE2-R binding inhibition, but a subset had levels <5,000 AU. Anti-S IgG levels >5,000 AU were associated with >90% ACE2-R binding inhibition and no documented breakthrough infections, whereas levels falling below 5,000 AU and approaching 1,000 AU were associated with breakthrough infections. Thus, quantitative antibody measurements may provide a means to guide vaccination intervals for the individual. IMPORTANCE Currently, clinicians have no guidance for the serologic assessment of SARS-Cov-2 postvaccination status regarding protection and risk of infection. Vaccination and boosters are administered blindly without evaluation of need or outcome at the individual level. The recent development of automated quantitative assays for anti-SARS-CoV-2 spike protein IgG antibodies permits accurate measurement of humoral immunity in standardized units. Clinical studies, such as reported here, will help establish protective antibody levels allowing identification and targeted management of poor vaccine responders and vaccinated subjects undergoing immune decay.

Evaluation of Tetanus Seropositivity in Healthcare Professionals by Age and Occupational Groups

Objective: Our country has limited data on protective antibody levels following primary tetanus immunization. In this study, we planned to evaluate the tetanus antibody seroprevalence of healthcare workers in our hospital according to age and occupational groups. Methods: Tetanus antibody levels were determined by the enzyme-linked immunosorbent assay (ELISA) method. Antibody results were obtained through the hospital operating system, and the tetanus antibody level ≥0.5 IU/mL was considered seropositive. Results: 77.5% of 2082 healthcare workers were seropositive. According to age groups, the highest seropositivity was between 20-29; the lowest seropositivity was found in individuals over 50 years of age and over (66.3%). We determined that tetanus antibody protection decreased with age (p=0.03). There was no difference between tetanus seropositivity according to occupational groups. Conclusion: Antibody levels of tetanus decrease with age, and protection decreases significantly, especially over 50 years of age. It is important to apply a booster dose every ten years following the primary vaccine schedule in tetanus immunization.

Sars-Cov-2 T-Cell Responses after One or Two COVID-19 Vaccine Boosters in Allogeneic Transplant Recipients

Introduction: The rapid availability of SARS-CoV-2 mRNA vaccines at the beginning of 2021 allowed to a relative protection of recipients of allogeneic stem cell transplantation (Allo-SCT) since up to 80% of patients developed anti-spike (anti-S) antibodies after two doses. In addition, cellular adaptive responses have also been documented after 2 shots. For example, we recently reported a strong response of specific anti-SARS-CoV-2- CD4+ T-cells, with a IFNγ-/TNFα+ cytokine profile, in 89% of humoral responders and 40% of non-humoral responders (Clemenceau, 2022). The interest of at least one booster has been confirmed thereafter with a persistent and significant reduced incidence of severe form or death due to COVID-19 infections. In this study, we have evaluated humoral and T-cell responses after one (Vaccine 3 or V3 group n=40) or two (Vaccine 4 or V4 group n=12) BNT162b2 mRNA vaccine boosters in 52 Allo-HSCT patients and in 12 healthy donors (only one booster). Methods: Blood samples were collected between January 18th and March 3rd 2022 during the Omicron wave in France. Anti- spike antibodies were tested using anti-SARS-CoV-2 immunoassay Elecsys® (Roche, Rotkreuz, Switzerland). Anti-SARS-CoV-2 Spike and anti-EBV (as positive control) specific CD3+ T-cell responses were evaluated using Human INFg ELIspot (Mabtech 3420-2AST-10, Nacka Strand, Sweden) and intracellular cytokine staining after peptide stimulation (PepTivator Prot_S Complete, Miltenyi Biotec, Bergisch Gladbach, Germany). Results Characteristics of the participants are summarized in Table 1. All controls (100%) and 81% of the whole patient cohort have developed a protective anti-S antibody level (>250 BAU/mL) after the boost vaccinations. The rate of subject reaching the highest antibody concentration (>2500 BAU/mL) was significantly higher in controls than the whole patient cohort (100% vs 52%, p=0.005) (Table 1). After the booster vaccination, 85% of patients and 100% of controls developed a specific-T cell response. Median frequency of anti-Spike T-cells was significantly lower for V3 patients (median: 0.028 spot forming units (SFU)/100 CD3+ T-cells, range 0.000-0.771) than in controls (median: 0.127 (range (0.006-0.235) (p=0.03) but not significantly different between V4 patients and V3 controls (p=0.03) (p=0.08) (Table 1 and Figure 1.A). We did not find a significant difference in the anti-SARS-CoV-2 T-cell frequency between patients whose analysis was done before 6 months after the last vaccination or those for whom the analysis was done after 6 months (Figure 1B). For 14 individuals with the highest frequencies of anti-Spike CD3+ T cells (³ 0.180 SFU/100 CD3+ T-cells), the Th1 cytokine profiles of CD3+, CD4+ and CD8+ T cells were performed by INFg, TNFa and IL-2 intracellular staining. A predominance of anti-spike CD4+ T-cell response was observed and, interestingly, a polyfunctional cytokine profile was observed in both controls (n=3), and patients (V3 n=6; V4 n=5) (Figure 1 C and D). The only factors predicting T-cell response in patients were CD8+ and NK cells counts at time of analyses. Surprisingly, higher counts were associated with no T-cell response. A good humoral response was not predictive of T cell response (75% vs weak response 82%, p=1). Importantly, considering the patients with no antibody response (n=5) or not reaching a protective antibody level after boosts (n=5), 8/10 (80%) had a measurable T-cell response. At time of last follow-up (June 1st 2022), 2 controls with a good humoral and T-cell response (0.125 and 0.235 SFU/100 CD3+ T-cells) have presented a non-severe COVID 19 infections. Similarly, two V3 patients presented with a non-severe form (negative serology and 0.039 SFU/100 CD3+ T-cells and serology >2500 BAU/mL and 0.040 SFU/100 CD3+ T-cells). One V3 patient with negative serology and 0.367 SFU/100 CD3+ T-cells at time of analysis have died of COVID-19 infection. Conclusion: In this cohort after one or two booster vaccination, 81% of patient achieved a protective humoral response while 85% achieved a T-cell response. T-cell frequencies were comparable between V4 patients and controls while COVID-19 infections were only observed in individuals with one booster. Although these results have to be confirmed on a larger cohort, it may indicate that two booster vaccines may help to achieve sufficient protection in allotransplanted patients through a persistent specific T cell response. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Breakthrough COVID-19 Infections in Patients with Hematologic Malignancies during the Omicron (B.1.1.529) Surge: Data from the Patient-Reported Leukemia & Lymphoma Society National Registry

INTRODUCTION We have previously observed that many patients with B-cell derived hematologic malignancies fail to produce protective levels of anti-spike antibodies or anti-spike T-cells in response to SARS-CoV-2 mRNA vaccination. We attempted to understand if these results indicated that such patients may be vulnerable to COVID-19 infections. METHODS The patient-reported LLS National Registry was used to identify patients who had COVID-19 infections including those whose infections occurred after vaccination (breakthrough infections or BTIs) and correlate the BTI with the level of anti-spike antibodies prior to the infection (NCT04806295, NCT04794387). The cohort consisted primarily of patients with chronic lymphocytic leukemia (43%) and other B-cell derived non-Hodgkin lymphomas (35%). Patients self-reported data on demographic variables, vaccine type(s) and dates of administration, date of COVID-19 infection, diagnostic method to detect the infection, and hospitalization date. Anti-spike antibody levels were assessed using the Roche Elecsys semi-quantitative assay. This study was approved by the Western Institutional Review Board, and participants provided informed consent electronically. This survey was conducted on February 17, 2022. RESULTS 2707 patients who were vaccinated, predominately with SARS-CoV-2 mRNA vaccines, responded to the survey. 295 out of 2707 (10.9%) patients reported BTIs (Figure 1). 80% of BTIs occurred during December 2021 to February 2022, a timing that coincided with the Omicron surge in the general US population. Of the 295 patients who had BTIs, 133/1177 (11.3%), 155/1464 (10.6%), and 7/66 (10.6%) of the patients had 2, 3 or 4 vaccinations, respectively. Among the 866 patients who had three vaccinations and anti-spike antibody analysis, 70 (8.1%) had BTIs. Compared to the population of patients that had three vaccinations who did not develop BTIs, 14/166 (8.2%) and 33/429 (7.6%) patients who had BTIs had undetectable (<0.8 U/mL) or very high levels (>2500 U/mL) of anti-spike antibodies, respectively. There was a moderate association between anti-spike antibody levels and time between 3rd vaccination and BTI (r2 = 0.064, P = 0.03; median values 114 to 138 days for non-detectable and maximum anti-spike levels, respectively). Hospitalizations were reported by 19 of 295 (6.4%) patients. Ten of these patients had anti-spike antibody analysis done after vaccination and prior to the BTI. 100% (10/10) of these patients had anti-spike antibody levels below detectable levels (N = 7) or low anti-spike antibody levels (range : 42-167 U/mL). Nine out of these ten patients had BTIs during the Omicron surge. CONCLUSIONS AND FUTURE DIRECTIONS Approximately 10% of patients with hematologic malignancies that had two to four SARS-CoV-2 vaccines reported a BTI during the Omicron surge. The percentage of BTIs was similar regardless of the anti-spike antibody level prior to the infection. In contrast, hospitalization due to a BTI was only found in patients with no detectable anti-spike antibodies or antibody levels previously known to be associated with poor neutralizing antibody levels. Further analysis is on-going to determine if these trends also occur during the BA.5 surge. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Transplacental transfer of total immunoglobulin G and antibodies to Plasmodium falciparum antigens between the 24th week of gestation and term

Full-term newborns have antibody (Ab) repertoires and levels similar to their mothers to help protect them from environmental pathogens. Unfortunately, preterm babies, especially those born < 34 weeks, have reduced levels of protective antibodies. In Africa, antibodies to Plasmodium falciparum are important in protection from malaria. This study investigated the transfer of total IgG and antibodies to 9 P. falciparum antigens and tetanus toxoid between 24 weeks and term. Paired maternal and cord samples from 166 preterm (24–37 weeks) and 154 term deliveries were used. Transfer efficiency was expressed as the ratio of Ab levels in cord to maternal plasma (CMR). At 24–25 weeks, CMR ranged from 0.31 to 0.94 for the different antigens; the rate of transfer was similar for all antigens between 24 and 40 weeks; resulting in median CMR of 0.49–0.95 at term. Babies of mothers with hypergammaglobulinemia and normal IgG levels had similar amounts of IgG, supporting data that saturation of the neonatal Fc-receptor occurs at ~ 16 mg IgG/ml. Thus, babies born prior to 34–35 weeks in Africa are likely to have reduced Ab levels to some, but not all antigens. Since IgG transfer is Fc-mediated, why differences exist in CMR among the antigens warrants further investigation.

Pitfalls in Understanding and Handling of Covid-19 Vaccination (“Any Fool Can Know. The Point Is to Understand”)

The aim of this article is to critically review the managing of vaccination over the course of the present COVID-19 pandemic against the knowledge that had already been at hand and the scientific data that had yet to be learned. In the period before vaccines for COVID-19 became available, the startling similarity in epidemiologic behavior between COVID-19 and the Spanish flu could be observed. The development of vaccines against COVID-19 has evolved at an unprecedented speed resulting in highly immunogenic vaccines with incredible protective characteristics covering a relatively short follow-up time in clinical trials. The rollout in the general population turned out to take significantly longer time than the duration of immunity conferred by a 2-dose vaccination schedule (about 3-4 months). Therefore, the SARS-CoV-2 was left with the opportunity for random mutations with each replication cycle, resulting in immune evasion, shortened incubation, shortened serial interval, and increased transmissibility. The short incubation period of COVID-19 requires a steady protective antibody titer to be maintained to avert infection, achieve herd immunity, and terminate the pandemic spread. The protective neutralization titer needed to avert symptomatic infection and infection altogether is about 3% and 20%, respectively, of the mean convalescent titer. The latter corresponds to an absolute titer of 1:10–1:30. The intensity and duration of protective vaccinal and hybrid humoral immunity are explored. From the present perspective, it was naive to believe that a 2-dose vaccination would suffice to counter COVID-19 primarily due to its short incubation and a roll-out that was not catching up with the waning protective vaccinal antibody levels. Besides, the spacing of doses and boosters with respect to previous infection or vaccination, and differences in natural immunity and vaccine-induced immunity (adenovirus-vectored and mRNA) are discussed. The issue of vaccination and multisystem inflammatory syndrome in children is briefly presented. Finally, ethical points are discussed as some vaccine production platforms and neutralization tests use human cell lines derived from aborted fetuses.Conclusion – If the COVID-19 vaccines had been licensed as 3-dose vaccines, with more generous spacing, e.g. 0-2-6 months, providing for quantitatively larger and temporally more durable humoral immunity, that would have enabled attaining a steadier herd immunity and probably a paradoxical earlier effect on stopping the transmission.

COVID-19 breakthrough infections in vaccinated participants of the Safety and Efficacy of Preventative COVID Vaccines sub-study.

The rate of breakthrough infection in vaccinated Ontarians during the Omicron wave is unknown. Active participants of the Safety and Efficacy of Preventative COVID Vaccines (STOPCoV) study (892 ≥age 70 years and 369 aged 30-50 years) were invited to participate in a sub-study evaluating breakthrough COVID-19 infection. Self-administered rapid antigen tests (RAT) were reported twice weekly and symptom questionnaires weekly for 6 weeks. The primary outcome was the proportion reporting a positive RAT. A total of 806 e-consented, and 727 (90%) completed ≥1 RAT, with total 7,116 RATs completed between January 28 and March 29, 2022. Twenty out of twenty-five participants with a positive RAT had a booster vaccine prior to the positive test. All cases were mild, none requiring hospitalization. Nineteen had positive dried blood spot analysis for IgG antibody to the receptor binding domain (RBD) prior to the positive RAT. The mean normalized IgG ratio to RBD was 1.22 (SD 0.29) for younger and 0.98 (SD 0.44) for older participants, values similar to corresponding ratios for those without positive RATs and those in the main cohort. One hundred and five participants reported one and 96 reported ≥2 possible COVID-19 symptoms despite negative RATs. The false negative RAT was low (4% to 6.6 %) compared with subsequent positive nucleoprotein antibody. Positive RAT for COVID-19 was infrequent (3.4%). We were unable to determine a protective antibody level against breakthrough infection. Our findings can inform public health COVID-19 restrictions guidelines. Our decentralized study provides a model for rapid institution of new questions during a pandemic.

Population immunity in residents of the Kaliningrad region to current antigenic variants of influenza viruses over 2018-2021

The article presents the results of population immunity assessment in residents of the Kaliningrad region to current antigenic variants of influenza viruses over the period of 2018 to 2021. To assess spectrum of influenza types circulating in Kaliningrad region, the real-time PCR method was used using AmpliSense reagent kits. The biological material for the study was obtained from oropharyngeal swabs from the persons who applied to polyclinics with inflammatory diseases of upper respiratory tract, or underwent treatment at the out- or inpatient basis in a healthcare facilities of Kaliningrad region. Humoral immunity was assessed by testing blood sera obtained from healthy residents of Kaliningrad region during periodic prophylactic examinations at the city and regional polyclinics. The study of residents covered all age groups. For the period of 2018-2021, more than 14,000 studies have been carried out. Determination of specific serum antibody titers was carried out by staging the hemagglutination suppression reaction using local influenza antigens (LLC PPDP, St. Petersburg). Antibody titers of 1/40 and higher were considered sufficient to reduce the risk of disease by 50%. During the study period, 2165 cases of influenza were confirmed in the region by laboratory tests. Over the study period, the A(H1N1) pdm serotype proved to be the major strain causing influenza, its proportion reached 57.5%. However, along with A(H1N1) pdm, a significant contribution was also made the A(H3N2) strain to the epidemic process, being the etiological cause of influenza infection in 2019 (42.2%), type B influenza strains being actual in 2020 (42.5%). Over the period of 2018-2021, 420 samples of blood sera from vaccinated and non-vaccinated individuals were tested for specific antibodies. The sera were taken 1-2 months after vaccination and between epidemic rises of influenza (April-May). In vaccinated individuals, the antibody titer was protective in 58.3-64.5%. In this group of persons, the titer sufficient to produce immunity was maintained over the spring/summer period. Among those persons who refused vaccination, a protective antibody titer in the pre-epidemic period was noted in 41.2% of the examined, and during the off-season it was detected in 37.4% of the volunteers. Thus, the A(H1N1) pdm strain was the main etiological factor of influenza in Kaliningrad Region in 2018-2021. The protective level of antibodies in vaccinated population over the period preceding the epidemic peak, was observed 30% more often than in unvaccinated individuals. High incidence of influenza B strains noted in 2020 appears to require a change of specific vaccine preparation.

Strong SARS-CoV-2 T-Cell Responses after One or Two COVID-19 Vaccine Boosters in Allogeneic Hematopoietic Stem Cell Recipients.

A full exploration of immune responses is deserved after anti-SARS-CoV-2 vaccination and boosters, especially in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although several reports indicate successful humoral responses in such patients, the literature is scarce on cellular specific immunity. Here, both B- (antibodies) and T-cell responses were explored after one (V3 n = 40) or two (V4 n = 12) BNT162b2 mRNA vaccine boosters in 52 allo-HSCT recipients at a median of 755 days post-transplant (<1 year n = 9). Results were compared with those of 12 controls who had received only one booster (BNT162b2 n = 6; mRNA-1273 n = 6). All controls developed protective antibody levels (>250 BAU/mL) and anti-spike T-cell responses. Similarly, 81% of the patients developed protective antibody levels, without difference between V3 and V4 (82.5% vs. 75%, p = 0.63), and 85% displayed T-cell responses. The median frequency of anti-spike T cells did not differ either between controls or the whole cohort of patients, although it was significantly lower for V3 (but not V4) patients. COVID-19 infections were solely observed in individuals having received only one booster. These results indicate that four vaccine injections help to achieve a satisfactory level of both humoral and cellular immune protection in allo-HSCT patients.

PFAS exposure and immunotoxic effects in children from Greenland

Background and aim: Perfluoroalkyl substances (PFAS) have been in production for more than half a century and is still used in numerous consumer products. Humans are exposed to PFAS through contaminated food and water as well as dust from treated materials. These chemicals bioaccumulate and are widespread in the environment, and populations relying on a marine diet are thus often more exposed. The aim of this study was to examine the association between Greenlandic children’s exposure to major environmental chemicals and their concentrations of diphtheria and tetanus vaccine antibodies after vaccination. Methods: The study is based on cross-sectional data from Greenlandic children aged 7–12 years examined during 2012–2015. Among 175 children with known vaccination records, 169 provided a serum sample with sufficient volume to measure PFAS and specific antibodies against diphtheria and tetanus. Associations were examined in linear and logistic regression models. Results: We found higher serum-PFAS concentrations to be associated with lower diphtheria antibody concentrations after vaccination and with increased odds of having diphtheria antibody concentrations below the protective level. For each 1 ng/mL increase in serum concentrations of perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA), odds of not having protective levels of diphtheria antibodies were increased 6.44 times (95 % CI: 1.51–27.36), 1.14 times (95 % CI: 1.04–1.26), 1.96 times (95 % CI: 1.07–3.60), and 5.08 times (95 % CI: 1.32–19.51, respectively. Conclusions: Our findings emphasize the risk of immunotoxicity associated with PFAS exposure also in this Arctic population. Keywords: PFAS, Children, Vaccine antibodies, Immunotoxicity, Greenland

Coronavirus Vaccination: Spike Antibody Levels in Health Workers after Six Months-A Cross-Sectional Study.

Healthcare workers bear a high risk of infection during epidemics and pandemics such as the current SARS-CoV-2 pandemic. Various new vaccines have been approved. We investigated the influence of the time elapsed since vaccination, as well as of vaccination schema, on health workers’ spike antibody levels following their second vaccination. Blood samples were obtained from employees working at a German hospital between August 2021 and December 2021 on average half a year (range 130–280 days) after their second vaccination. Levels of SARS-CoV-2-IgG antibodies (spike and nucleocapsid protein) were qualitatively detected via chemiluminescent immunoassays (CLIAs). A previous infection with SARS-CoV-2 was an exclusion criterion. In total, 545 persons were included in this cross-sectional study. Most participants (97.8%) showed elevated anti-spike concentrations. Anti-spike levels differed significantly among vaccination schemas. Repeated vector vaccinations resulted in lower protective antibody levels. Higher age levels, immunosuppression and a longer time period since the second vaccination resulted in lower anti-spike levels. Women’s antibody levels were higher, but not significantly. Since anti-spike levels drop after vaccination, further boosters are required to increase immunoreactivity. If two vector vaccines have been administered, it is possible that an mRNA booster might increase the anti-spike level.

Persistence of protective anti-poliovirus antibody levels in 4-year-old children previously primed with Picovax®, a trivalent, aluminium-adjuvanted reduced dose inactivated polio vaccine

BackgroundTo meet the demand for effective and affordable inactivated polio vaccines (IPVs), a reduced dose, aluminium hydroxide (Al(OH)3)-adjuvanted IPV vaccine was developed (IPV-Al, Picovax®) and evaluated in clinical trials. The present trial is an extension of two previous trials (a primary and a booster trial). The aim was to evaluate the persistence of seroprotective antibodies (poliovirus type-specific antibody titre ≥ 8) in 4-year-old children who previously received IPV–Al as primary and booster vaccine doses and to determine the potential booster response and safety profile of an additional dose of IPV-Al. MethodsChildren participating in the two previous trials were invited to receive one additional dose of IPV-Al at 4 years of age (2.5 years after the booster dose) and to have their blood samples collected to measure the pre- and post-vaccination antibody titres. Systemic adverse events (AEs) and local reactogenicity were recorded. ResultsAt study entry, the seroprotection rates were 89.2%, 100% and 91.1% against poliovirus type 1, 2 and 3, respectively. The additional vaccination with IPV-Al boosted the level of poliovirus type 1, 2 and 3 antibodies to above the seroprotection threshold for all but one subject, i.e., 99.4% for type 1 and 100% for types 2 and 3. The additional dose induced a robust booster response of a 26.3-, 13.9- and 30.9-fold increase in titre for poliovirus types 1, 2 and 3, respectively. The vaccine was well tolerated, with only mild and transient AEs reported. ConclusionsThe present trial demonstrated that the primary vaccination with an aluminium-adjuvanted reduced dose IPV induced a persistent immune memory as evidenced by the robust anamnestic response when the subjects were re-exposed to the antigen 2.5 years after the last dose. Thus, the IPV-Al is an efficient and safe addition to increase the availability of inactivated polio vaccines globally. (ClinicalTrials.gov reg no. NCT04448132).