Evaluation of Transplacental Antibody Transfer in SARS-CoV-2-Immunized Pregnant Women

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy could result in adverse perinatal outcome. Clinical data on the assessment of the immune response in vaccinated pregnant women and subsequent transplacental antibody transfer are quite limited. Objective: To assess maternal and neonatal neutralizing antibody levels against both wildtype and Delta (B.1.617.2) variants after maternal mRNA vaccination. Study Design: This cohort study was conducted 29 pregnant women who were vaccinated at least one dose of Moderna (mRNA-1273) vaccine. Both neutralizing antibody (wildtype and Delta variant) and S1 receptor binding domain IgG antibody levels were evaluated in maternal and cord blood on the day of delivery. Results: Superiority of antibody level was significant in fully vaccinated women compared with the one-dose group (maternal sera, median, 97.46%; cord sera, median, 97.37% versus maternal sera, median, 4.01%; cord sera, median, 1.44%). No difference in antibody level was noted in relation to interval of second immunization to delivery in the two-dose group (95.99% in 0–2 weeks, 97.45% in 2–4 weeks, 97.48% in 4–8 weeks, 97.72% in 8–10 weeks). The most pronounced reduction was observed for the Delta variant. The wildtype neutralizing antibody level of full-vaccinated women was not influenced by the pertussis vaccination. Conclusion: The data underscore the importance of full vaccination in pregnancy and support the recommendation of COVID-19 immunization for pregnant women. The lower level of vaccine-induced neutralizing antibodies for the Delta variant indicates insufficient protection for mother and newborn and highlights the need for development of effective vaccine strategies.

The recombinant pseudorabies virus expressing porcine deltacoronavirus spike protein is safe and effective for mice

Background Porcine deltacoronavirus (PDCoV) is a new pathogenic porcine intestinal coronavirus, which has appeared in many countries since 2012. PDCoV disease caused acute diarrhea, vomiting, dehydration and death in piglets, resulted in significant economic loss to the pig industry. However, there is no commercially available vaccine for PDCoV. In this study, we constructed recombinant pseudorabies virus (rPRVXJ-delgE/gI/TK-S) expressing PDCoV spike (S) protein and evaluated its safety and immunogenicity in mice. Results The recombinant strain rPRVXJ-delgE/gI/TK-S obtained by CRISPR/Cas gE gene editing technology and homologous recombination technology has genetic stability in baby hamster syrian kidney-21 (BHK-21) cells and is safe to mice. After immunizing mice with rPRVXJ-delgE/gI/TK-S, the expression levels of IFN-γ and IL-4 in peripheral blood of mice were up-regulated, the proliferation of spleen-specific T lymphocytes and the percentage of CD4+ and CD8+ lymphocytes in mice spleen was increased. rPRVXJ-delgE/gI/TK-S showed good immunogenicity for mice. On the seventh day after booster immunity, PRV gB and PDCoV S specific antibodies were detected in mice, and the antibody level continued to increase, and the neutralizing antibody level reached the maximum at 28 days post- immunization (dpi). The recombinant strain can protect mice with 100% from the challenge of virulent strain (PRV XJ) and accelerate the detoxification of PDCoV in mice. Conclusion The recombinant rPRVXJ-delgE/gI/TK-S strain is safe and effective with strong immunogenicity and is expected to be a candidate vaccine against PDCoV and PRV.

Myasthenia gravis associated with a pelvic follicular lymphoma

An 81-year-old woman presented with neck weakness, dysarthria, dysphasia and left-sided ptosis. Myasthenia gravis (MG) was strongly suspected. Voltage gated calcium channel (VGCC) antibodies, associated with Lambert-Eaton myasthenic syndrome (LEMS), were negative. Acetylcholine receptor (AChR) antibody level was 536 nmol/L and diagnosis of MG was confirmed. Imaging revealed a pelvic mass and subsequent biopsy confirmed a pelvic follicular lymphoma. Our searches revealed this to be the first documented case of MG associated with a pelvic follicular lymphoma. She underwent radiotherapy to treat the lymphoma and received both pyridostigmine and immunosuppression to treat the MG. Her AChR antibody level decreased to 38 nmol/L and her MG symptoms resolved aside from head drop which is continuing to improve. Her lymphoma is now in remission. We have presented a case with a successful outcome, which highlights the importance of screening for lymphoma and thymoma in new presentations of MG.

Anti-CCP antibody in rheumatoid arthritis patients and its relation with severity of the disease

Background: Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by chronic and erosive polyarthritis causing irreversible joint disability. It is the most common persistent inflammatory arthritis, affecting from 0.5 to 1% of the general population worldwide. Antibodies to citrullinated proteins (anti-CCP antibody) have been described in patients with RA and these appear to be the most specific marker of the disease. Methods: This cross-sectional study was carried out at department of medicine, Sher-E-Bangla Medical College Hospital, Barisal Form July’ 2016 to December’ 2016. All rheumatoid arthritis patients attending at OPD and those got admitted under Medicine Dept, who was satisfying the inclusion and exclusion criteria were included consecutively and purposively in this study. Results: Total 70 cases were included; the mean age was found 46.57±13.10 years in anti-CCP antibody positive group and 44.19±11.21 years in anti-CCP antibody negative group. Female were predominant in both groups. Duration of disease was around 8 years in both groups. Mean ESR was 29.0±22.0 mm in anti-CCP antibody positive group and 12.25±10.6 mm in anti-CCP antibody negative group. Mean rheumatoid factor was 189.4±102.1 U/L in anti-CCP antibody positive group and 66.5±36.0 U/L in anti-CCP antibody negative group. Mean DAS 28 score was 4.6±1.4 and 3.6±1.3 in anti-CCP antibody positive and negative group respectively. The mean difference was statistically significant (p<0.05) between the groups. Patients in disease remission had lower anti-CCP antibody titer than those with low, moderate or high disease activity. Significantly positive correlation (r=0.596; p=0.001) between severity of rheumatoid arthritis and anti CCP antibody level was observed. Conclusion: In RA patients’ disease was more severe in anti-CCP antibody positive group and significantly positive correlation between anti-CCP antibody level with disease severity of RA was observed. BIRDEM Med J 2022; 12(1): 36-40

CURRENT STRATEGIES OF USING MAJOR NON-ANTIBODY IMMUNITY SYSTEMS AGAINST DISEASES ACCOMPANYING COVID-19

The main dominated factors and strategies of non-antibody immunity (the human innate and others, microbial probiotic) aimed at maintaining and strengthening health in connection with the pandemic disease COVID-19 are considered and currently systematized. An integrated current evaluation of the non-antibody immunity is given and preventive and therapeutic approaches to its use for combating diseases accompanying COVID-19 (or on the it’s background) are indicated. Innate immunity is considered as the basic and deep support for the antibody level immunity as the higher and super-structure. The concept of increasing sensitivity to be infected with COVID-19 in population groups depending on the presence and/or the progress of spectrum pathologies and diseases and in connection with the waves of the pandemic COVID-19 is proposed.

DISAPPEARANCE OF ANTIBODIES IN COVID-19 MYTHS ORREALITY

Objective: To explore the disappearance of neutralizing antibodies from patients, their myths, and facts. Study Design: Cross-sectional study. Place and Duration of Study: Combined Military Hospital Multan Pakistan, from Jul 2021 to Aug 2021. Methodology: A total of 100 blood samples were collected from 100 COVID-19 patients. These 100 patients were followed up for a period of 3 months. Antibodies were determined with the modified neutralization assay method and enzyme-linked immuno-sorbent assay (ELISA). Results: The antibody level by NA and ELISA peaked on days 30-35 then decreased slightly. In multivariate analysis, patients aged 25-35, 36-56, and 57-84 years had a higher neutralizing antibody level than those aged 10-21 years. The patient with the worst clinical manifestation had a higher neutralizing antibody titer. In serum samples, IgG was undetectable at 18.3% and 11% and the geographical mean reciprocal titers dropped from 244 at 3-month period and neutralizing antibodies, the geographical mean reciprocal titers dropped from 874 at 3 months. Conclusion: All COVID-19 patients were seropositive and significantly neutralizing antibody response. Neutralizing antibody levels depend on the time after the onset of symptoms, age, and severity of the disease.

Antibody-Dependent Enhancement of SARS-CoV-2 Infection of Human Immune Cells: In Vitro Assessment Provides Insight in COVID-19 Pathogenesis

Patients with COVID-19 generally raise antibodies against SARS-CoV-2 following infection, and the antibody level is positively correlated to the severity of disease. Whether the viral antibodies exacerbate COVID-19 through antibody-dependent enhancement (ADE) is still not fully understood. Here, we conducted in vitro assessment of whether convalescent serum enhanced SARS-CoV-2 infection or induced excessive immune responses in immune cells. Our data revealed that SARS-CoV-2 infection of primary B cells, macrophages and monocytes, which express variable levels of FcγR, could be enhanced by convalescent serum from COVID-19 patients. We also determined the factors associated with ADE, and found which showed a time-dependent but not viral-dose dependent manner. Furthermore, the ADE effect is not associated with the neutralizing titer or RBD antibody level when testing serum samples collected from different patients. However, it is higher in a medium level than low or high dilutions in a given sample that showed ADE effect, which is similar to dengue. Finally, we demonstrated more viral genes or dysregulated host immune gene expression under ADE conditions compared to the no-serum infection group. Collectively, our study provides insight into the understanding of an association of high viral antibody titer and severe lung pathology in severe patients with COVID-19.

IMMUNOGRAPH-BASED ANALYSIS OF THE INFLUENZA A (H1N1)PDM09 VACCINE STRAIN IMMUNOGENICITY IN THE PANDEMIC AND POST-PANDEMIC PERIOD (2009-2014)

Currently, the assessment of the immunogenic properties of influenza viruses as a part of influenza vaccines, is carried out by using seroprotection, seroconversion as well as the rate of increases in post-vaccination antibodies. At the same time, significant differences in the immunogenicity of vaccines related to dynamic formation of high antibody titers responsible for long-term protection of the vaccinated, are neglected.Influenza viruses such as A (H1N1) pdm09 that caused 2009-2010 pandemic continue to circulate in the population, therefore, the assessment of the immunogenic activity of vaccine viruses prepared during the pandemic period is interesting in for the methodology to prepare pandemic vaccines to be used in various groups (adults, children, elderly people).Analyzing immunogenicity of influenza vaccines used during the 2009-10 swine influenza pandemic and the post-pandemic period up to the year 2014 was carried out by applying the graphical method for assessing immunogenicity (immunographs) measured as follows: for each group of vaccinated subjects (depending on the vaccine used), an increased rate in antibody level was calculated and the graphs of immunogenicity were plotted. An increased rate of serum antibodies magnitude from vaccinated subjects and the number of sera (in%) with a given fold increase rate in antibody level from 1 to the maximum magnitude were plotted on the x- and y-axis, respectively. The proposed method for assessing immunogenicity allows to plot immunogenicity graphs regardless of the serum antibodies level found in volunteers. The assessment described above revealed a several features for developing immune response to the pandemic virus A (H1N1)pdm09 such as the lack of immune response in a substantial number of adult volunteers (25-27%%) and young children (60-70%%) after monovaccine administration. The reason for such immune response can be both an insufficient dose of vaccine-containing viral antigen and suppressed immune response caused by the influenza A(H1N1)pdm09.A study on the immunogenic properties for seasonal influenza vaccines containing the influenza A (H1N1) pdm09 virus antigen in the years 2010 - 2014 revealed a variety in emerging humoral immunity ranging from a short-term, low-frequency increase in antibodies from vaccinated children to the formation of high antibody titers in elderly.Practically, immunographic analysis of influenza vaccines particularly those derived from the influenza A (H1N1)pdm09 virus, may result in proposing recommendations to increase an antigenic load at the beginning of a pandemic cycle and/or block the suppressive properties of vaccine-contained viruses in pediatric vaccines, because escalating virus dose in the vaccine may not always be achievable in this case.