Specific Humoral Immunity Research Articles

Heterogeneity of SARS-CoV-2 immune responses after the nationwide Omicron wave in China.

It remains unclear how previous infections and vaccinations influenced and shaped heterogeneous immune responses against Omicron and its variants in diverse populations in China. After the national wave of Omicron in early 2023, we evaluated serum levels of neutralizing antibodies (nAbs) against Omicron (B.1.1.529) and its variants (BA.5, BF.7, and CH1.1) in 33 COVID-19 convalescents and 40 uninfected vaccinees, using vesicular stomatitis virus-based pseudovirus neutralizing assay. In addition, we followed 34 Delta convalescent patients to compare their immune responses against Omicron before (late 2021) and after the Omicron wave (early 2023). NAbs at the acute phase of the disease were investigated in 50 Omicron inpatients, including 24 vaccinated and 26 unvaccinated patients. Among them, nasal mucosal IgA levels were measured in 42 subjects. Compared to vaccination, breakthrough infections significantly increased the breadth and magnitude of serum nAbs and mucosal IgA levels against Omicron variants. Exposure to Omicron but not Delta elicited stronger pan-Omicron responses. In Omicron inpatients, nAbs continued to rise as vaccination doses increased. However, in both vaccinees and convalescents, a fourth dose vaccination did not elicit higher nAbs against Omicron. Furthermore, nAbs against Omicron variants lasted longer than nAbs against WT SARS-CoV-2. Breakthrough infections of Omicron variants elicited specific immune responses against Omicron compared to vaccination and Delta infection. Although repeated vaccination revealed limited impacts on serum nAbs, populations at high risk of hospitalization may still benefit from continued vaccination.IMPORTANCEThe study described the specific humoral immunity against Omicron and its variants (BA.5, BF.7, and CH1.1) in diverse populations, including Delta-positive convalescent patients, Omicron-infected patients with a previous or current confirmed Delta infection, Omicron-positive patients, and healthy controls. In addition, we followed Delta convalescents for 1 year to evaluate the effect of a booster vaccine, breakthrough infection, and reinfection. Nasal mucosal IgA levels against SARS-CoV-2 were also examined. The findings of this study demonstrated the varied responses of individuals in different states following the outbreak of Omicron, highlighting the potential advantages of ongoing immunization for groups that are more vulnerable and have a greater likelihood of being hospitalized.

Phase I Clinical Study of the Subunit Betulin-Adjuvanted Tetravalent Candidate Influenza Vaccine TetraFluBet.

This study aimed to determine the safety, tolerability and immunogenicity of TetraFluBet, an inactivated subunit influenza vaccine that contains a corpuscular immuno-adjuvant derived from natural betulin. We conducted a prospective, randomized, open-labeled, single-center, phase I trial. The study was conducted in two stages: 5 volunteers in stage I and 25 volunteers in stage II. Eligible participants received one single dose (20 μg/0.5 mL) of TetraFluBet intramuscularly. Participants were followed for adverse events and reactogenicity. Seroconversion rate, seroprotection level, geometric mean titers (GMTs) of virus-neutralizing antibodies, IFN-γ induction and cell-mediated immunity were assessed. A total of 30 participants were enrolled. No vaccine-related serious adverse events were observed. The proportions of study participants with 4-fold seroconversions assessed by the HI assay (with 95% CIs) were 80.0% (62.7; 90.5), 70.0% (52.1; 83.3), 63.3% (45.5; 78.1) and 73.3% (55.6; 85.8) for influenza virus subtypes A (H1N1), A (H3N2), B1 and B2, respectively. Seroprotection levels (with 95% CIs) were 83.3% (66.4; 92.7), 83.3% (66.4; 92.7), 73.3% (55.6; 85.8) and 66.7% (48.8; 80.8), respectively. The fold increases in the GMTs of virus-neutralizing antibodies for subtype H1N1 was 6.50, for subtype H3N2 was 3.03, for subtype B1 was 3.56 and for subtype B2 was 6.07. The population of cytotoxic T-cells increased significantly in the post-vaccination period, indicating a strong CD3+CD8+ response. TetraFluBet tetravalent inactivated subunit vaccine with adjuvant demonstrated pronounced immunogenic properties, leading to the formation of both specific humoral and cellular immunity at a 20 μg dose.

A candidate tick-borne encephalitis virus vaccine based on virus-like particles induces specific cellular and humoral immunity in mice1

Tick-borne encephalitis (TBE) is an important zoonotic viral disease transmitted by ticks. In recent decades, global climate change has increased human exposure to ticks, and mortality rates have gradually risen. Effective vaccines are essential for controlling TBE as specific antiviral treatment is unavailable. Vaccine candidates based on virus-like particles (VLPs) have previously been demonstrated to be efficient in eliciting excellent immune responses against influenza virus and SARS-CoV-2. Here, we constructed TBE virus (TBEV) VLPs containing the envelope and membrane proteins derived from the Far Eastern TBEV strain (WH2012) using an insect cell-baculovirus expression system. Induction of immune responses was investigated in mice following intramuscular injection with the TBEV VLPs vaccine candidates formulated of Poly(I:C) & Montanide ISA 201VG combination adjuvants. Mice produced memory T-cells and serum-specific IgG antibodies that averaged up to 1:104.6 and remained at 1:104 (mean) for 24 weeks after three immunizations. TBEV VLPs vaccine was able to provide long-term antibody protection against TBEV, making it a promising subunit vaccine candidate for this disease.

Курение подростков как фактор риска снижения адаптационных ресурсов метаболизма нейтрофилов ротовой полости и прогрессирующего течения рецидивирующего бронхита

High prevalence of smoking among children and its early onset is an urgent problem in modern pediatrics. For proper health risk quantification, it is extremely important to understand and parameterize relationships between effects of adverse factors and physiological processes in the body, including the cellular level. The aim of this study was to analyze how tobacco smoking influences maladaptive changes in the mucosal immunity system of the oral cavity in adolescents and to assess kinetic trends in the clinical course of recurrent bronchitis (RB) in long-term outlook. The study included 92 patients with RB aged 16.8 ± 3.1 years. Two groups were created of them; the observation group was made of 64 patients, who admitted smoking as a habit, and the reference group included 28 people without nicotine addiction. The control group was made of 23 adolescents of the same age without any signs of the analyzed disease. Oral neutrophils (N) were selected as basic research material. N oxygen metabolism was registered by luminol-dependent chemiluminescence (LDCL) in spontaneous (sLDCL) and induced (iLDCL) variants. Functional N probing was performed using opsonized zymosan (Σ) and and peptidoglycan from S. aureus strain Cowan. Concentrations of antibodies (AT) to glycolipid (GLP) (Re-mutant Salmonella Minnesota), Candida albicans and S. аureus were determined by ELISA tests. The analyses made it possible to detect a close relationship between levels of ROS generation by neutrophilic granulocytes and the immune components of anti-endotoxic immunity. Immune changes were not established to be universal in the groups of examined patients and were shown to reflect the specificity of destabilizing effects produced by tobacco smoke. A direct moderate correlation was established in the observation group between sLDCL indicators and the concentration of anti-candidosis antibodies (r = +0.59, p = 0.0382), which reflects the level of bacterial stimulation involving dysbiotic shifts in gut microbiota. A direct correlation was detected between levels of biocidal parameters of neutorphil granulocytes and anti-glycolipid levels (r = +0.64 p = 0.417). Integral assessment of specific humoral immunity to glycolipid and the phagocytic link of the mucosal protection in the oral cavity reflects the degree of endogenous intoxication and kinetic trends in the RB clinical course in adolescents in subsequent years of life. These relationships may provide solid rounds for ‘exposure – response’ stage in the risk assessment procedure for assessing risks of respiratory diseases in smoking adolescents.

Algorithm for assessing the level of T cell immune response against SARS-CoV-2 and the results of its application in unvaccinated and vaccinated people who have been infected with COVID-19

Antigen (AG)-specific T cell activity was compared in two groups of patients: those who underwent COVID-19 in 2021 during the circulation of the SARS-CoV-2 delta virus strain (43 individuals); and those who underwent COVID-19 in 2022 (Omicron strain, 23 individuals). The diagnosis was confirmed by PCR analysis of nasopharyngeal and oropharyngeal swabs. The 23 individuals following COVID-19 caused by SARS-CoV-2 (omicron) were part of a cohort of 41 volunteers who were examined multiple times during 2021–2023: during vaccination, after vaccination, before revaccination, and subsequently after illness (6–8 times in total). Due to this, it was possible to compare the indices of specific humoral and cellular immunity in the same patients 1–2 months before and after breakthrough infection. Detection of AG-specific T cells and assessment of their activity by AG-stimulated IFNγ production was carried out by our own previously developed method (Patent RU № 2780369 C1). For stimulation of memory T effectors in vitro, the same antigens were used to determine the concentration of antibodies against SARS-CoV-2 by ELISA method. A total of about 300 blood samples from healthy subjects and patients after COVID-19 were analyzed. Each sample was tested against 3 SARS-CoV-2 antigens and in 2 stimulation modes. A qualitative assessment algorithm for AG-specific T cell activity has been proposed that can be used to monitor the state of cellular immunity in a population in which SARS-CoV-2 virus continues to circulate and to create insights into what level of T cell activation is sufficient to prevent or reduce the severity of SARS-CoV-2 infection. Unvaccinated COVID-19 (SARS-CoV-2, Delta) survivors lacked AG-specific T cells to RBD SARS-CoV-2, but T cell specificity to full-length S glycoprotein at the same level, qualitatively assessed as low in 52% of the group, persisted for up to six months. In previously unvaccinated COVID-19 vaccinees, this duration of persistence of AG-specific T cells in circulating blood was achieved only after revaccination. Hybrid immunity, which we traced as a result of vaccination after COVID-19 (Delta strain) or as a breakthrough infection (SARS-CoV-2, Omicron), is characterized by the highest indices of memory T cell activity (43–46% of the group — normal activity of AG-specific cells, 30–43% — high activity) to all used antigens and the longest duration of preservation of indices at this level. Further investigation of the level of antiviral immunity after COVID-19 may be important for predicting the outcome of new waves of SARS-CoV-2 infection.

Specific immunological characteristics and risk factor of XBB variants re-infection in nasopharyngeal carcinoma patients after BA.5 infection

ObjectivesThe specific humoral immune response resulting from inactivated vaccination following by BA.5 infection, and predictors of XBB variants re-infection in BA.5 infection-recovered nasopharyngeal carcinoma (BA.5-RNPC) patients, were explored. MethodsSerum SARS-CoV-2 specific antibody levels were assessed using enzyme-linked-immunosorbent-assay. Univariate and multivariate binary logistic regression analyses were conducted to identify factors associated with the magnitude of specific humoral immunity and susceptibility to re-infection by XBB variants. ResultsOur data demonstrates that SARS-CoV-2 specific antibody levels were comparable between BA.5-RNPC patients and BA.5 infection-recovered-non-cancerous (BA.5-RNC) individuals. Specifically, serum levels of anti-ancestral-S1-IgG, anti-ancestral-nucleocapsid-protein (NP)-IgG, anti-BA.5-receptor binding domain (RBD)-IgG and anti-XBB.1.1.6-RBD-IgG were higher in BA.5-RNPC patients compared to those without a prior infection. Compared to BA.5-RNPC patients without vaccination, individuals who received inactivated vaccination exhibited significantly higher levels of anti-ancestral-S1-IgG and anti-XBB.1.16-RBD-IgG. Multivariate logistic regression analysis revealed that inactivated vaccination was the most significant predictor of all tested SARS-CoV-2 specific antibodies response. Subsequent analysis indicated that a low globulin level is an independent risk factor for XBB re-infection in BA.5-RNPC patients. ConclusionsThe SARS-CoV-2 specific antibodies have been improved in vaccinated BA.5-RNPC patients. However, the baseline immunity status biomarker IgG is an indicators of XBB variant re-infection risk in BA.5-RNPC patients.

Design of a New Vaccine Prototype against Porcine Circovirus Type 2 (PCV2), M. hyopneumoniae and M. hyorhinis Based on Multiple Antigens Microencapsulation with Sulfated Chitosan.

This work evaluated in vivo an experimental-multivalent-vaccine (EMV) based on three Porcine Respiratory Complex (PRC)-associated antigens: Porcine Circovirus Type 2 (PCV2), M. hyopneumoniae (Mhyop) and M. hyorhinis (Mhyor), microencapsulated with sulfated chitosan (M- ChS + PRC-antigens), postulating chitosan sulphate (ChS) as a mimetic of the heparan sulfate receptor used by these pathogens for cell invasion. The EMV was evaluated physicochemically by SEM (Scanning-Electron-Microscopy), EDS (Energy-Dispersive-Spectroscopy), Pdi (Polydispersity-Index) and zeta potential. Twenty weaned pigs, distributed in four groups, were evaluated for 12 weeks. The groups 1 through 4 were as follows: 1-EMV intramuscular-route (IM), 2-EMV oral-nasal-route (O/N), 3-Placebo O/N (M-ChS without antigens), 4-Commercial-vaccine PCV2-Mhyop. qPCR was used to evaluate viral/bacterial load from serum, nasal and bronchial swab and from inguinal lymphoid samples. Specific humoral immunity was evaluated by ELISA. M-ChS + PRC-antigens measured between 1.3-10 μm and presented low Pdi and negative zeta potential, probably due to S (4.26%). Importantly, the 1-EMV protected 90% of challenged animals against PCV2 and Mhyop and 100% against Mhyor. A significant increase in antibody was observed for Mhyor (1-EMV and 2-EMV) and Mhyop (2-EMV), compared with 4-Commercial-vaccine. No difference in antibody levels between 1-EMV and 4-Commercial-vaccine for PCV2-Mhyop was observed. Conclusion: The results demonstrated the effectiveness of the first EMV with M-ChS + PRC-antigens in pigs, which were challenged with Mhyor, PCV2 and Mhyop, evidencing high protection for Mhyor, which has no commercial vaccine available.

Biofunctional lipid nanoparticles for precision treatment and prophylaxis of bacterial infections.

The lack of bacterial-targeting function in antibiotics and their prophylactic usage have caused overuse of antibiotics, which lead to antibiotic resistance and inevitable long-term toxicity. To overcome these issues, we develop neutrophil-bacterial hybrid cell membrane vesicle (HMV)-coated biofunctional lipid nanoparticles (LNP@HMVs), which are designed to transport antibiotics specifically to bacterial cells at the infection site for the effective treatment and prophylaxis of bacterial infection. The dual targeting ability of HMVs to inflammatory vascular endothelial cells and homologous Gram-negative bacterial cells results in targeted accumulation of LNP@HMVs in the site of infections. LNP@HMVs loaded with the antibiotic norfloxacin not only exhibit enhanced activity against planktonic bacteria and bacterial biofilms in vitro but also achieve potent therapeutic efficacy in treating both systemic infection and lung infection. Furthermore, LNP@HMVs trigger the activation of specific humoral and cellular immunity to prevent bacterial infection. Together, LNP@HMVs provide a promising strategy to effectively treat and prevent bacterial infection.

Self-Assembling Sulfated Lactobacillus Exopolysaccharide Nanoparticles as Adjuvants for SARS-CoV-2 Subunit Vaccine Elicit Potent Humoral and Cellular Immune Responses.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic since its onset in 2019, and the development of effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to induce potent and long-lasting immunity remains a priority. Herein, we prepared two Lactobacillus exopolysaccharide (EPS) nanoparticle adjuvants (NPs 7-4 and NPs 8-2) that were constructed by using sulfation-modified EPS and quaternization-modified chitosan. These two NPs displayed a spherical morphology with sizes of 39 and 47 nm. Furthermore, the zeta potentials of NPs 7-4 and NPs 8-2 were 50.40 and 44.40 mV, respectively. In vitro assays demonstrated that NPs could effectively adsorb antigenic proteins and exhibited a sustained release effect. Mouse immunization tests showed that the NPs induced the expression of cytokines and chemokines at the injection site and promoted the uptake of antigenic proteins by macrophages. Mechanically, the NPs upregulated the expression of pattern recognition receptors (toll-like receptors and nod-like receptors) and activated the immune response of T cells and the production of neutralizing antibodies. In addition, the NP adjuvants had favorable immune-enhancing effects in cats, which are of great significance for controlling the trans-host transmission and re-endemicity of SARS-CoV-2. Overall, we demonstrated that NP-adjuvanted SARS-CoV-2 receptor binding domain proteins could induce robust specific humoral and cellular immunity.

JANUS KINASE INHIBITORS FOR RELAPSING POLYCHONDRITIS TREATMENT: A HYPOTHESIS

Relapsing polychondritis (RP) is a rare autoimmune disease marked by recurrent episodes of inflammation impacting cartilaginous structures. The underlying mechanism has not been fully elucidated; however, comprehensive genetic and histopathological evaluations have revealed the involvement of specific genes, cell-mediated immunity, and humoral immunity in the pathogenesis of RP. The spectrum of symptoms associated with this condition ranges from mild manifestations to severe, life-threatening presentations. Treatment options vary depending on the disease severity. Non-steroidal anti-inflammatory drugs, colchicine, dapsone, and systemic corticosteroids are commonly utilized as first-line therapeutic options. Furthermore, cyclophosphamide, methotrexate, azathioprine, cyclosporine, and biological disease-modifying anti-rheumatic drugs are employed as second-line treatment. Nevertheless, there is insufficient data regarding the use of Janus kinase inhibitors (JAKi) in RP patients as a treatment option. This hypothesis suggests that JAKi may be a viable treatment option for relieving symptoms in these patients.

Pediococcus pentosaceus MIANGUAN Enhances the Immune Response to Vaccination in Mice.

Increasing evidence shows that some probiotics can improve vaccine responses as adjuvants. This study aimed to evaluate the effect of Pediococcus pentosaceus MIANGUAN (PPM) on SARS-CoV-2 vaccine-elicited immune response in mice. Six-week-old female ICR mice were primed and boosted with SARS-CoV-2 vaccine intramuscularly at weeks 0 and 4, respectively. Mice were gavaged with PPM (5 × 109CFU/mouse) or PBS (control) for 3days immediately after boosting vaccination. Compared to the control, oral PPM administration resulted in significantly higher levels of RBD-specific IgG binding antibodies (> 2.3-fold) and RBD-specific IgG1 binding antibodies (> 4-fold) in the serum. Additionally, PPM-treated mice had higher titers of RBD-specific IgG binding antibodies (> 2.29-fold) and neutralization antibodies (> 1.6-fold) in the lung compared to the control mice. The transcriptional analyses showed that the B cell receptor (BCR) signaling pathway was upregulated in both splenocytes and BAL cells in the PPM group vs. the control group. In addition, the number of IFN-γ-producing splenocytes (mainly in CD4 + T cells as determined by flow cytometry) in response to restimulation of RBD peptides was significantly increased in the PPM group. RNA sequencing showed that the genes associated with T cell activation and maturation and MHC class II pathway (CD4, H2-DMa, H2-DMb1, H2-Oa, Ctss) were upregulated, suggesting that oral administration of PPM may enhance CD4 + T cell responses through MHC class II pathway. Furthermore, PPM administration could downregulate the expression level of proinflammatory genes. To conclude, oral administration of PPM could boost SARS-CoV-2 vaccine efficacy through enhancing the specific humoral and cellular immunity response and decrease the expression of inflammation pathways.

Promising directions in the development of new vaccines against papillomavirus infection

Papillomavirus infection is one of the most common viral infections worldwide. Highly oncogenic types of human papillomavirus (HPV) are the root cause of cancer of the cervix, vulva, vagina, genitals in men, anal cancer, as well as cancer of the oropharyngeal region. Currently, three HPV vaccines have been registered and successfully used in Russia: divalent (HPV types 16, 18) and quadrivalent (HPV types 6, 11, 16, 18). In the countries of America and Europe, a nine-valent vaccine is available, which contains nine types of HPV (6, 11, 16, 18, 31, 33, 45, 52, 58). These vaccines are preventive, have high immunogenicity and induce the production of specific antibodies. The action of preventive vaccines is aimed at creating specific humoral immunity to the capsid proteins of the virus, which leads to the prevention of HPV infection. Nevertheless, there are no specific medicines on the pharmaceutical market aimed at treating an already established pathology.
 Currently, active development of HPV vaccines with both preventive and therapeutic effects is underway. Candidates of therapeutic HPV vaccines undergo various stages of research. Experimental vaccination systems on animal models provide encouraging results. If preventive and therapeutic HPV vaccines prove to be effective in patients as well as in animal models, then pillomavirus infection and related malignant diseases can be controlled by vaccination.

The long-lasting Ascaris suum antigens in the lungs shapes the tissue adaptation modifying the pulmonary architecture and immune response after infection in mice

Ascariasis is the most prevalent helminth affecting approximately 819 million people worldwide. The acute phase of Ascariasis is characterized by larval migration of Ascaris spp., through the intestinal wall, carried to the liver and lungs of the host by the circulatory system. Most of the larvae subsequently transverse the lung parenchyma leading to tissue injury, reaching the airways and pharynx, where they can be expectorated and swallowed back to the gastrointestinal tract, where they develop into adult worms. However, some larvae are trapped in the lung parenchyma inciting an inflammatory response that causes persistent pulmonary tissue damage long after the resolution of infection, which returns to tissue homeostasis. However, the mechanism by which chronic lung disease develops and resolves remains unknown. Here, using immunohistochemistry, we demonstrate that small fragments and larval antigens of Ascaris suum are deposited and retained chronically in the lung parenchyma of mice following a single Ascaris infection. Our results reveal that the prolonged presence of Ascaris larval antigens in the lung parenchyma contributes to the persistent immune stimulation inducing histopathological changes observed chronically following infection, and clearly demonstrate that larval antigens are related to all phases of tissue adaptation after infection: lung injury, chronic inflammation, resolution, and tissue remodeling, in parallel to increased specific humoral immunity and the recovery of lung function in mice. Additional insight is needed into the mechanisms of Ascaris antigen to induce chronic immune responses and resolution in the host lungs following larval migration.

STATE OF HUMORAL IMMUNITY IN DIABETIC RETINOPATHY AGAINST THE BACKGROUND OF THE METABOLIC SYNDROME

Introduction. The most common cause of vision loss in case of diabetes is retinal pathology (diabetic retinopathy). The study of blood pressure levels in blood serum in patients with nonproliferative diabetic retinopathy in type 2 diabetes is a promising direction of research with the aim of studying the links of the pathogenesis of the development of this pathology, diagnosis, and possible prognosis of the disease
 The aim of the study: to find out the peculiarities of humoral immune dysfunction in patients with diabetic retinopathy against the background of metabolic syndrome
 Results and discussion. PSA increases in patients with decompensated diabetes (by 1.2 times compared to the control group). We found a statistically significant increase in the level of Ig A in patients of group 2 by 2.5 times compared to the control group and by 1.5 times compared to group 1. The content of Ig M exceeds the control indicator by 2.3 times and in group 1 by 1.7 times. The level of Ig G increased compared to the control indicator by 1.4 times, and did not differ from the indicator in group 1. The content of CIC in group 2 exceeded the indicators in the control group by 1.4 times and by 2 times the indicators in group 1, which indicates a higher probability of occurrence of III-type hypersensitivity reactions in the group of non-insulin-dependent patients with DR.
 Probable strong correlations of the concentration of immunoglobulins with other indicators in group 2 were revealed, which may indicate the preservation of relationships between immune indicators in compensated diabetes.
 The analysis of the ratio of the indicators implies the predominant activation of a specific link of humoral immunity and suggests the chronicity of the process, in the group of non-insulin-dependent patients there is a pronounced activation of humoral protection on the mucous membranes, as well as a predominant activation of early humoral immune mechanisms.
 Conclusion. Determination of the content of humoral factors of immunity in blood serum often does not reveal a probable difference. Therefore, it is advisable to determine the ratio of indicators. The obtained data indicate more pronounced changes in indicators of specific humoral immunity - immunoglobulins in patients with diabetic retinopathy, compared to the indicator of systemic inflammation - SRP.

Class switch towards spike protein-specific IgG4 antibodies after SARS-CoV-2 mRNA vaccination depends on prior infection history

Vaccinations against SARS-CoV-2 reduce the risk of developing serious COVID-19 disease. Monitoring spike-specific IgG subclass levels after vaccinations may provide additional information on SARS-CoV-2 specific humoral immune response. Here, we examined the presence and levels of spike-specific IgG antibody subclasses in health-care coworkers vaccinated with vector- (Sputnik, AstraZeneca) or mRNA-based (Pfizer-BioNTech, Moderna) vaccines against SARS-CoV-2 and in unvaccinated COVID-19 patients. We found that vector-based vaccines elicited lower total spike-specific IgG levels than mRNA vaccines. The pattern of spike-specific IgG subclasses in individuals infected before mRNA vaccinations resembled that of vector-vaccinated subjects or unvaccinated COVID-19 patients. However, the pattern of mRNA-vaccinated individuals without SARS-CoV-2 preinfection showed a markedly different pattern. In addition to IgG1 and IgG3 subclasses presented in all groups, a switch towards distal IgG subclasses (spike-specific IgG4 and IgG2) appeared almost exclusively in individuals who received only mRNA vaccines or were infected after mRNA vaccinations. In these subjects, the magnitude of the spike-specific IgG4 response was comparable to that of the spike-specific IgG1 response. These data suggest that the priming of the immune system either by natural SARS-CoV-2 infection or by vector- or mRNA-based vaccinations has an important impact on the characteristics of the developed specific humoral immunity.

SARS-CoV-2 specific plasma cells acquire long-lived phenotypes in human bone marrow

SARS-CoV-2 specific antibody-secreting plasma cells (PC) mediating specific humoral immunity have been identified in the human bone marrow (BM) after COVID-19 or vaccination against SARS-CoV-2. However, it remained unclear whether or not they acquire phenotypes of human memory plasma cells. SARS-CoV-2-specific human bone marrow plasma cells (BMPC) were characterised by tetramer-based, antigen-specific flow cytometry and FluoroSpot assay. SARS-CoV-2 spike-S1-specific PC were detectable in all tested BM samples of previously vaccinated individuals, representing 0.22% of total BMPC. The majority of SARS-CoV-2-specific BMPC expressed IgG and their specificity for the spike S1 protein indicated emergence from a systemic vaccination response. Of note, one-fifth of SARS-CoV-2-specific BMPC showed the phenotype of memory plasma cells, i.e., downregulated CD19 and present or absent CD45 expression. Our data indicate the establishment of phenotypically diverse SARS-CoV-2-specific PC in the human BM after basic mRNA immunization, including the formation of memory phenotypes. These results suggest the induction of durable humoral immunity after basic mRNA vaccination against SARS-CoV-2. The study was supported by funding by the DFG grants TRR130 TP24, ME 3644/8-1, and the Berlin Senate. SR received funding from DFGSFB-1444 C01 Central Service Project.

The effectiveness of medical personnel vaccination against hepatitis B

Medical personnel belong to the occupational risk group of hepatitis B virus (HBV) infection due to the increase of parenteral interventions and procedures using sophisticated equipment, constant contact with biological fluids of patients, the widespread use of antibiotics and cytostatics that have an immunosuppressive effect, etc. Insufficient objectivity in assessing the quality of hepatitis B (HBV) immunoprophylaxis only according to documentation may be associated with a violation of immunization regimens, the presence of chronic pathology in vaccinated, age-related immunodeficiency. Despite the effectiveness of HCV vaccination, the protective activity of specific humoral immunity (antibodies to HBsAg — anti-HBs) among vaccinated medical workers has not been sufficiently studied. The results of studying the intensity and duration of the immune response in 2075 employees of two large multidisciplinary hospitals vaccinated against HBV (average age 46.3 ± 10.1 years) are presented. A high level of vaccination coverage of medical personnel in hospitals No. 1 and No. 2 was established, amounting to 96.6 % and 97.2 %, and the level of collective immunity was equal to 1645.5±72.5 IU/l and 886±123.7 IU/l, respectively. The absence of cases of HBV in vaccinated individuals during immunoprophylaxis according to the standard scheme was noted. It seems advisable to use an individual approach to the tactics of revaccination when reducing the content of anti-HBs in the blood to low concentrations (10–100 IU / l), preventing them from falling below the protective level.

A tale of two conditions: when people living with HIV meet three doses of inactivated COVID-19 vaccines.

Currently, data on long-term immune responses to a homogenous booster dose of the inactivated COVID-19 vaccine are still limited among people living with HIV (PLWH). A prospective cohort study with a 13-month follow-up was conducted in China between March 2021 and August 2022 to evaluate the dynamics of SARS-CoV-2 specific humoral and cellular immunity against three doses of the inactivated COVID-19 vaccine from before the first dose until 6 months after the booster dose vaccination among PLWH in comparison to healthy controls (HC). 43 PLWH on antiretroviral therapy (ART) and 23 HC were enrolled. Compared with HC, the neutralizing antibodies (nAbs) levels among PLWH were significantly lower on days 14, 30, 60, 90, and 120 after the booster dose vaccination. Among PLWH, the nAbs titers on days 14, 30, and 60 after the booster dose were significantly higher than the peak of the second dose. However, on day 180 after the booster dose, the nAbs titers were similar to the peak of the second dose vaccination. Compared with HC, the frequencies of IFN-γ-secreting and TNF-α-secreting CD4+ and CD8+ T cells among PLWH were lower on days 14 and 180 after the booster dose vaccination. Among PLWH, increased T cell immunity was induced by the booster dose of the vaccine and kept stable on day 180 after the booster dose vaccination. Although a homogenous booster dose following two doses of the inactivated COVID-19 vaccine among PLWH could elicit higher nAb titers, reduce antibody decay, and maintain T cell responses even 6 months after vaccination, the overall immunogenicity of the booster dose was found to be lower among PLWH than among healthy controls. Further strategies are needed to improve immunogenicity to the inactivated COVID-19 vaccine among PLWH.

Clinical characteristics and host immunity responses of SARS-CoV-2 Omicron variant BA.2 with deletion of ORF7a, ORF7b and ORF8

BackgroundThe pathogenicity and virulence of the Omicron strain have weakened significantly pathogenesis of Omicron variants. Accumulating data indicated accessory proteins play crucial roles in host immune evasion and virus pathogenesis of SARS-CoV-2. Therefore, the impact of simultaneous deletion of accessory protein ORF7a, ORF7b and ORF8 on the clinical characteristics and specific immunity in Omicron breakthrough infected patients (BIPs) need to be verified.MethodsHerein, plasma cytokines were identified using a commercial Multi-cytokine detection kit. Enzyme-linked immunosorbent assay and pseudovirus neutralization assays were utilized to determine the titers of SARS-CoV-2 specific binding antibodies and neutralizing antibodies, respectively. In addition, an enzyme-linked immunospot assay was used to quantify SARS-CoV-2 specific T cells and memory B cells.ResultsA local COVID-19 outbreak was caused by the Omicron BA.2 variant, which featured a deletion of 871 base pairs (∆871 BA.2), resulting in the removal of ORF7a, ORF7b, and ORF8. We found that hospitalized patients with ∆871 BA.2 had significantly shorter hospital stays than those with wild-type (WT) BA.2. Plasma cytokine levels in both ∆871 BA.2 and WT BA.2 patients were within the normal range of reference, and there was no notable difference in the titers of SARS-CoV-2 ancestor or Omicron-specific binding IgG antibodies, neutralizing antibody titers, effector T cells, and memory B cells frequencies between ∆871 BA.2 and WT BA.2 infected adult patients. However, antibody titers in ∆871 BA.2 infected adolescents were higher than in adults.ConclusionsThe simultaneous deletion of ORF7a, ORF7b, and ORF8 facilitates the rapid clearance of the BA.2 variant, without impacting cytokine levels or affecting SARS-CoV-2 specific humoral and cellular immunity in Omicron-infected individuals.

Outcome prediction of the measles vaccination in healthcare employees

Vaccination is the only guarantee for elimination of measles infection. Healthcare workers have a 13- to 19-fold higher risk for contracting measles than the general population. The number of individuals in the population who did not respond to vaccination is up to 10%, and their accumulation may lead to an outbreak of the infection. The aim of our research was to find potential predictors of arising post-vaccination measles antibodies in the panel of biochemical and immunological serum markers in healthcare workers. The group of healthcare workers (n = 76) aged from 19 to 51 years, with proven absence of pre-existing anti-measles antibodies were twice vaccinated 3 months apart with live measles culture vaccine (SPA “Microgen”, Russia). Measles-specific IgG, total IgG, IgM, IgA, IFNγ, IL-6, CRP, total protein, ALT, AST, total bilirubin, urea, creatinine, protein fractions were determined before vaccination, 1 month after vaccination, 1 month following revaccination, 1 year after revaccination. ROC analysis was used to gain access to the diagnostic performance of quantitative variables in predicting a categorical outcome. Development of a predictive probability model for the binary outcome was carried out using logistic regression. IFNγ, total IgG, IgM, total bilirubin, ALT activity at various post-immunization stages may be considered potential laboratory predictors of measles vaccination failures in healthcare workers. Meanwhile, the contents of pre-vaccination IFNγ, and IgG to measles virus after first vaccination proved to be most informative indexes, which formed the basis for the development of regression models predicting the risk of both primary and secondary vaccination failures. These models allowed to develop algorithm for predicting failures of the measles vaccination in healthcare workers that can be used for detection of persons at risk for non-forming specific humoral immunity. This algorithm is primarily focused on search for the persons who have not responded to measles vaccination, including subjects with probable immunodeficiency conditions. We do not exclude that, on the basis of revealed predictors following measles vaccination, it would be possible to build prognostic models of vaccination efficiency for other vaccinemanaged infections.