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Patients with 2019 coronavirus disease (COVID-19) exhibit a broad spectrum of clinical presentations. A person's antimicrobial antibody profile, as partially shaped by past infection or vaccination, can reflect the immune system health that is critical to control and resolve the infection. We performed an explorative immunoproteomics study using microbial protein arrays displaying 318 full-length antigens from 77 viruses and 3 bacteria. We compared antimicrobial antibody profiles between 135 patients with mild COVID-19 disease and 215 patients with severe disease in 3 independent cohorts from Mexico and Italy. Severe disease patients were older with higher prevalence of comorbidities. We confirmed that severe disease patients elicited a stronger anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) response. We showed that antibodies against HCoV-229E and HcoV-NL63 but not against HcoV-HKU1 and HcoV-OC43 were also higher in those who had severe disease. We revealed that for a set of IgG and IgA antibodies targeting coronaviruses, herpesviruses, and other respiratory viruses, a subgroup of patients with the highest reactivity levels had a greater incidence of severe disease compared to those with mild disease across all three cohorts. On the contrary, fewer antibodies showed consistent greater prevalence in mild disease in all 3 cohorts. IMPORTANCE The clinical presentations of COVID-19 range from asymptomatic to critical illness that may lead to intensive care or even death. The health of the immune system, as partially shaped by past infections or vaccinations, is critical to control and resolve the infection. Using an innovative protein array platform, we surveyed antibodies against hundreds of full-length microbial antigens from 80 different viruses and bacteria in COVID-19 patients from different geographic regions with mild or severe disease. We not only confirmed the association of severe COVID-19 disease with higher reactivity of antibody responses to SARS-CoV-2 but also uncovered known and novel associations with antibody responses against herpesviruses and other respiratory viruses. Our study represents a significant step forward in understanding the factors contributing to COVID-19 disease severity. We also demonstrate the power of comprehensive antimicrobial antibody profiling in deciphering risk factors for severe COVID-19. We anticipate that our approach will have broad applications in infectious diseases.
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COVID-19, caused by the novel SARS-CoV-2 virus, poses major challenges for global public health. The detection of antibodies in blood serum is one of the important methods for diagnostics of COVID-19 patients. The main aim was to study the dynamics of the appearance of neutralizing antibodies and antibodies to the SARS-CoV-2 proteins in COVID-19 patients sera. Material and methods. The blood sera of four groups of people were studied: "intact" donors (blood sera were collected in 2016-2019);patients with a laboratory-confirmed diagnosis of acute respiratory viral infection;patients with influenza (antibodies to the influenza virus have been identified) and patients with a PCR confirmed diagnosis of COVID-19. Blood sera were analyzed in ELISA with commercial kits for detection of IgG to SARS-CoV-2 (N, S) proteins and total antibodies to RBD of protein S and in neutralization test (NT). Results and discussion. Antibodies to SARS-CoV-2 were not detected in paired blood sera of people from groups 1-3 by ELISA and NT. At the time of hospitalization of patients with COVID-19 in the sera of 12 (19%) patients antibodies to SARS-CoV-2 were absent when they were determined by NT and ELISA. In blood sera taken 4-9 days after hospitalization, neutralizing antibodies and antibodies to at least one viral protein were detected in ELISA. Conclusion. At the time of hospitalization, the overwhelming majority of patients had a humoral immune response to the SARS-CoV-2. In the dynamics of observation, the levels of antibodies to SARS-CoV-2 proteins increased, to a greater extent to RBD.Copyright © 2022 Geotar Media Publishing Group
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The analyses of effectiveness of medical means of protection based on virus specific antibodies, intended for special prophylactic and current of COVID-19 is conducted. The plasma of patients, obtained from the blood takes the leading part among these prepares. It is concluded, that convalescents plasma, containing virus neutralizing antibodies, may be used for emergency prevention or in the early stages of the disease. A risk group, that primarily needs in such drugs for special prophylactics, is medical workers. The other prepares, based on virus specific antibodies, including purified prepares of monoclonal antibodies, that may have certain advantages to convalescent's plasma due to their safety and high activity, due to complexity of their production and presumably high cost are unlikely to be available in the near future for mass use in the practice of medicine. The use of convalescents plasma for the prevention and treatment of COVID-19.can be based on the experience of their application in specialized medical centers and summarizing data from randomized clinical trials.Copyright © 2021 Moscow State University of Psychology and Education. All right reserved.
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To combat infectious diseases, vaccines are considered the best prophylactic strategy for a wide range of the population, but even when vaccines are effective, the administration of therapeutic antibodies against viruses could provide further treatment options, particularly for vulnerable groups whose immunity against the viruses is compromised. Therapeutic antibodies against dengue are ideally engineered to abrogate binding to Fcγ receptors (FcγRs), which can induce antibody-dependent enhancement (ADE). However, the Fc effector functions of neutralizing antibodies against SARS-CoV-2 have recently been reported to improve post-exposure therapy, while they are dispensable when administered as prophylaxis. Hence, in this report, we investigated the influence of Fc engineering on anti-virus efficacy using the anti-dengue/Zika human antibody SIgN-3C and found it affected the viremia clearance efficacy against dengue in a mouse model. Furthermore, we demonstrated that complement activation through antibody binding to C1q could play a role in anti-dengue efficacy. We also generated a novel Fc variant, which displayed the ability for complement activation but showed very low FcγR binding and an undetectable level of the risk of ADE in a cell-based assay. This Fc engineering approach could make effective and safe anti-virus antibodies against dengue, Zika and other viruses.
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Asymptomatic infections with SARS-CoV-2 are associated with viral transmission and have a key role in the propagation of the pandemic. Understanding viral shedding during asymptomatic infections is critical. Unfortunately, data on asymptomatic SARS-CoV-2 infection in children is extremely limited. To determine the presence of viral viable shedding, we prospectively followed two healthy children of a family where both parents developed mild COVID-19 (April 2021). SARS-CoV-2 detection was made by RT-PCR and virus isolation by cell culture from saliva samples. Positive samples were sequenced to identify variants of SARS-CoV-2. Serum samples were evaluated to determine the presence of antibodies using a single enzyme-linked immunosorbent assay (ELISA, COVIDAR IgG). Both children were SARS-CoV-2 positive and asymptomatic. In addition, the virus grew in cell culture from saliva samples. Furthermore, one child showed viable SARS-CoV-2 for at least 17 days after the onset symptoms from his father. The recommended isolation period for asymptomatic contacts during the acquisition of data had been established for 10 days;however, this child remained with viable virus beyond that period. The positive samples from both children were consistent with B.1.1.28.1 lineage (Gamma). In both asymptomatic children, anti-Spike IgG was detected. Asymptomatic children may represent a source of infection that should not be underestimated during this pandemic. Las infecciones asintomáticas por SARS-CoV-2 están asociadas a la transmisión viral y tienen un papel clave en la propagación de la pandemia. Comprender la excreción viral durante las infecciones asintomáticas es fundamental. Desafortunadamente, los datos sobre la infección asintomática por SARS-CoV-2 en niños son extremadamente limitados. Para determinar la presencia de excreción de virus viable, se siguió prospectivamente a dos niños sanos de una familia en la que ambos padres desarrollaron COVID-19 leve (abril 2021). La detección de SARS-CoV-2 se realizó por RT-PCR y el aislamiento del virus por cultivo celular a partir de muestras de saliva. Las muestras positivas se secuenciaron para identificar variantes de SARS-CoV-2. En las muestras de suero se determinó la presencia de anticuerpos utilizando un ensayo de ELISA (COVIDAR IgG). Ambos niños fueron positivos para SARS-CoV-2 y asintomáticos. Además, el virus creció en cultivos celulares a partir de muestras de saliva. Uno de los niños mantuvo SARS-CoV-2 viables durante al menos 17 días después de la aparición de los síntomas de su padre. El período de aislamiento recomendado para contactos asintomáticos durante la adquisición de datos se había establecido en 10 días, sin embargo, este niño permaneció con virus viable más allá de ese período. Las muestras positivas de estos niños correspondieron al linaje B.1.1.28.1 (Gamma). En ambos niños asintomáticos se detectó anticuerpos IgG anti-Spike. Concluimos que los niños asintomáticos pueden representar una fuente de infección que no debe subestimarse durante esta pandemia.
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Background Management of patients with multiple sclerosis (MS) and evidence of disease activity during treatment with cladribine tablets represents a challenging point. Objectives To report a patient with highly active multiple sclerosis (HAMS) who has been early switched from cladribine to alemtuzumab owing to tumultuous clinical and radiological activity Methods A single retrospective case report. Results. Treatment with alemtuzumab has led to a complete suppression of disease activity without any evidence of infections or acquired autoimmune diseases. Conclusion Our report suggests that an early switch from cladribine to alemtuzumab, may be safe and efficacious in selected HAMS cases.Copyright © 2022 The Authors
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Influenza is an infectious respiratory disease caused by influenza A and B, which is a virus characterized by a high mutation rate with new strains appearing regularly, making regular booster vaccinations necessary. In this study, we evaluated the immune status of Influenza A and B by using ELISA. A questionnaire was utilized to appraise the immunization anamnesis and the stance on vaccination. In total, 202 probands participated in this study. 35.6% of the probands were vaccinated, 10.9% indicated a confirmed influenza infection. 88.1% had a positive influenza A titer, whereas a positive influenza B titer was determined in only 38.6%. Additionally, a correlation between vaccination and titer could be observed. In this study, we were able to show a higher vaccination rate in our cohort than the Austrian average. Additionally, a higher percentage showed a positive influenza A titer compared to influenza B titer.Copyright © 2022
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Introduction and Objectives: Strategies to simplify the care circuit for patients with the hepatitis C virus (HCV) are vital to achieving its eradication. To achieve this aim, we introduced an electronic system of HCV serology detection to link diagnosis with specialized assistance in order to minimize the loss of patients. Material(s) and Method(s): A retrospective single-center study of HCV patients developed by Microbiology Department from February 15th, 2020, to December 15th, 2021. In the event of a positive HCV antibody, the anti-HCV core was directly measured by the electronic system. If positive, an encrypted e-mail with the patient data was automatically sent to HCV specialized physicians, who, after evaluating the benefits of antiviral therapy in each patient, contacted them by phone for an appointment. In the first face-to-face consultation FibroScan, HCV genotype and viral load measurement were performed, and antiviral therapy was prescribed. Patient diagnosis origin and public health characteristics were recorded. We analyzed the association between antiviral therapy prescription and these variables. Statistical significance was set at p<0.005. Result(s): Of 171 patients identified, with a mean age of 59.6 +/- 15.9, 61.5 % of males and 81.2% of Spanish nationals. HCV origin from out-of-hospital settings predominated (50.9%, 87/171), particularly primary care (28.7%), penitentiary (11.6%) and addiction units (8.2%). In all, 43.3% (74/171) were aware of their diagnosis, but 64.9% (48/74) hadn't previously received antiviral therapy. Genotype 1 predominated. We recorded 19.4% (20/103) of patients F3 fibrosis and 27.2% (26/103) F4. Finally, 58.5% (100/171) attended a physician consultation. They were all treated with pangenotypic interferon-free therapy. A 100% rate of sustained viral response was achieved. The main reasons for not being treated were high comorbidity (43.7%,31/71), not located (23.9%, 17/71), patient refusal to treatment (23.9%,17/71) and death (8.5%,6/71). The sole association found between antiviral therapy and patient variables was that of comorbidities with being untreated (OR=7.14, p<0.001). Conclusion(s): Our alert system is simple and easily reproducible. It allows for minimizing the loss of HCV patients, even considering it was performed during the COVID-19 pandemic.Copyright © 2023
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A 20-year-old patient was presented with subacute onset of headache, nausea and vomiting. Testing of nasal/oropharyngeal swabs indicated the presence of SARS-CoV-2 RNA, and later the antibodies to this virus were found. The treatment in the hospital for Coronavirus 19 Disease (COVID-19) provided only temporary relief, and the patient then was referred to the Regional Stroke Center (RSC) to exclude a subarachnoid hemorrhage. RSC neurologists drew attention to multiple skin nevi in the patient. Brain MRI demonstrated abnormal T1 hyperintensity in the brain leptomeninges, with leptomeningeal contrast enhancement as well as hyperintensity in amygdala regions on T1 weighted images, bilaterally. The anomaly of the Dandy-Walker malformation complex was also revealed. Cerebrospinal fluid (CSF) analysis showed elevated protein (0.52 g/L), low lymphocytosis (lymphocytes, 6 in mm3), and decreased glucose (1.8 mmol/L). Neurocutaneous melanocytosis (NCM) was diagnosed, which neurological manifestation was probably triggered by COVID-19. The patient's vision gradually progressively worsened. In 2.5 months after the clinical manifestation of NCM, fundoscopy revealed optic discs atrophy (despite the absence of previous edema), and repeated CSF analysis showed atypical cells with characteristics corresponding to melanoma. Malignant transformation of cerebral melanocytosis was suspected, and the patient was referred to an oncological dispensary for further therapy. In the presented literature review, special attention is paid to the issues of neuroimaging, cytological and immunocytochemical diagnostics of NCM.Copyright © Russian Neurological Journal. All rights reserved.
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By April 28, 2020, the global pandemic of COVID-19 has resulted in over 3 million infections and more than 200, 000 deaths. As the epidemic of COVID-19 has been basically controlled in China, the asymptomatic infection becomes one of most serious challenges for "External defense input, internal defense rebound" currently. Studies have shown that patients with asymptomatic infections are highly contagious in the early stage, most of whom are in the pre-symptomatic stage. Children and pregnant women have a higher incidence of asymptomatic infections, but the impacts are not yet clear. This article reviews the definition, epidemiological characteristics, contagiousness, viral shedding and cause of persistent positive nucleic acid in asymptomatic patients. Active detection of nucleic acids and antibodies and timely diagnosis and treatment of asymptomatic cases are the critical issues for the prevention and control of COVID-19.Copyright © 2020 by the Chinese Medical Association.
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By April 28, 2020, the global pandemic of COVID-19 has resulted in over 3 million infections and more than 200, 000 deaths. As the epidemic of COVID-19 has been basically controlled in China, the asymptomatic infection becomes one of most serious challenges for "External defense input, internal defense rebound" currently. Studies have shown that patients with asymptomatic infections are highly contagious in the early stage, most of whom are in the pre-symptomatic stage. Children and pregnant women have a higher incidence of asymptomatic infections, but the impacts are not yet clear. This article reviews the definition, epidemiological characteristics, contagiousness, viral shedding and cause of persistent positive nucleic acid in asymptomatic patients. Active detection of nucleic acids and antibodies and timely diagnosis and treatment of asymptomatic cases are the critical issues for the prevention and control of COVID-19.Copyright © 2020 by the Chinese Medical Association.
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Introduction and Objectives: In Argentina, it is estimated that around 50% of patients infected with hepatitis C virus (HCV) have been diagnosed and only 5% of those have accessed treatment after several months;this reality got worse with the pandemic. World Health Organization proposed a global health sector strategy to eliminate HCV as a public health threat by 2030. Key elements of the elimination plan include increased diagnosis and treatment access. This study aimed to describe the implementation of "Relinkage and simplified care pathway program" as a strategy for micro-elimination of HCV. Material(s) and Method(s): : Hospital outpatients aged over 18 years, with a confirmed or suspected diagnosis of HCV infection and without follow-up during the last year, were included. Patient selection was made by collecting data from medical records. Selected patients were contacted by telephone and scheduled for a clinic visit with a simplified care pathway. "Reflex Testing," which is an HCV antibody test, was used;if the result was positive, an HCV RNA and genotype test on the same specimen was performed. Untreated and non-responder patients were treated. Result(s): : A total of 938 patients were included, and 409 (44%) could be reached. Out Of these, 16.3% (67) died, 1.7% (7) developed hepatocellular carcinoma, and 6.75% (15) progressed to cirrhosis. We found that 21.7% were candidates for treatment, and the treatment was delivered in two clinic visits with an average time of 29 days (7-69). However, 41% (34) of patients with cirrhosis could not be contacted. Conclusion(s): : Program implementation improved the diagnosis and treatment access. Furthermore, it reduces the number of clinical visits and may increase adherence to follow-up. On the other hand, we are concerned that half of the patients were lost on the follow-up and about their progression to cirrhosis rate. If we are looking for different results, we should take different measures.Copyright © 2023
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Feline Infectious Peritonitis (FIP)is a fatal disease caused by Feline coronaviruses. The causative agent is Feline Infectious Peritonitis Virus, a mutation of Feline Enteric Coronavirus. Feline Corona Virusinfection is very common in the cat population.In Feline Corona Virus infected cats, the development of FIP depends on the cat's immune response. FIP disease is more common in young and old cats because young and old animals have a weaker immune system. The acute phase response is a complex systemic reaction that occurs as a response to acute or chronic inflammatory processes such as infection, neoplasia or immunological disorders, tissue damage, trauma, and surgery. The study material was composed of15 cats with FIP (study group) and 10 healthy cats (control group). Serum amyloid A (SAA), haptoglobin (Hp), alpha1-acid glycoprotein (AGP), albumin, interleukin-6 (IL-6), hepcidin, alanine-amino transferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen(BUN), and creatinine levels were measured in the serum collected from both groups. There was no difference between the wet and dry FIP in albumin values (p<0.05).Haptoglobin, alpha1-acid glycoprotein, SAA, IL-6, and hepcidin values were significantly different between the two groups (P<0.001). It was also concluded that hepcidinhas a potential for use as a biomarker in Feline Infectious Peritonitis disease like other acute phase proteins.Copyright © 2023, Sima Sahinduran, Metin Koray Albay, Mehmet Karaca, Mehmet Cagri Karakurum, Reyda Kiyici
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Background: Data are limited regarding the safety of and antibody response to the BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger ribonucleic acid vaccine in adolescents and young adults with underlying disease. Methods: This prospective observational study enrolled patients age 12–25 years with chronic underlying disease who received 2 doses of BNT162b2. A 18-item questionnaire was used to assess adverse events within 7 days post-vaccination, and data regarding severe adverse events were collected from electronic medical records. An antibody titer for the receptor-binding domain of the spike protein in SARS-CoV-2 was used to assess antibody response after the second vaccine dose. Results: Study participants were 429 patients (241 [56.2%] age 12–15 years;188 [43.8%] age 16–25 years). The most common underlying diseases were genetic or chromosomal abnormalities and/or congenital anomalies, followed by endocrine or metabolic diseases;32% of participants were immunocompromised. Severe adverse events were observed after the second dose in 1 (0.4%) patient age 12–15 years and in 2 (1.1%) patients age 16–25 years;all patients recovered. Seropositivity after the second vaccine dose was 99.0%. The geometric mean antibody titer was higher in patients age 12–15 years versus 16–25 years (1603.3 [1321.8–1944.7] U/mL vs. 949.4 [744.2–1211.0] U/mL). Compared with immunocompetent patients, immunocompromised patients had a lower antibody titer (2106.8 [1917.5–2314.7] U/mL vs. 467.9 [324.4–674.8] U/mL). Conclusions: Vaccination with BNT162b2 was acceptably safe and immunogenic for adolescents and young adults with underlying disease. © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases
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Vaccines having aided in escaping the majority of the population from immunological naïvety, our strategies are now shifting towards an increased focus on identifying and protecting the extremely vulnerable. We here describe the results of testing 12 patients, those with lymphoid malignancies having been targeted their B-cells for therapy with rituximab-containing regimens or a Bruton tyrosine kinase inhibitor, for anti-SARS-CoV-2 spike antibodies after receiving the BNT162b2 mRNA vaccine doses. The interval from last dosing of B-cell depletion therapy to SARS-CoV-2 vaccination was at median 5.3 (range 3.1–6.6) months. Using the ‘seroprotection' threshold of 775 [BAU/mL] for the anti-spike antibody titer, our finding points out the crucial unresponsiveness of the targeted population with 0/12 (0%) achieving ‘seroprotection'. Although IgG seroconversion was observed in 4/12 (33%), supporting the overall benefit of vaccination, the figures still point out a potential need for optimization of practice. IgA was further less responsive (unsuccessful ‘seroconversion' in 11/12 (92%)), implicating an underlying class switch defect. Those with depletion on B-cells are caught at a dilemma between, being too early and too late on receiving SARS-CoV-2 vaccines. They wish to get over their immunological naïvety at the earliest, while, in order to assure quality immune memory, are also required to hold the patience for their B-cells to repopulate. Although it remains an issue whether intensified vaccine schedules and/or regimens will lead to stronger immunogenicity or more effective boosters for non-responders, we shall take advantage of every increasing evidence in order to optimize current options. © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases
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Background: To mitigate the COVID-19 pandemic, many countries have recommended the use of booster vaccinations. The relationship between the degree of adverse vaccine reactions and elevated antibody titers is of interest;however, no studies have investigated the temporal changes in antibody titers based on repeated measurements after a third dose of the BNT162b2 vaccine. Methods: This prospective longitudinal cohort study was conducted with 62 healthcare workers who received a third dose of the BNT162b2 at Okayama University Hospital, Japan. Venous blood draw and fingertip whole blood test sample collection were conducted at the early (3–13 days) and 1-month time points;only FWT sample collection was conducted at the 2-month time point. Information on adverse reactions within 1 week after vaccination was also obtained. The association between fever of 37.5 °C or higher and antibody titers after the third dose of BNT162b2 was examined using a mixed-effects model and Poisson regression with robust variance. Results: A trend toward higher antibody titers in the early period after vaccination was observed in the febrile individuals, but the differences were not significant at 1 and 2 months post-vaccination (the partial regression coefficient for fever was 8094.3 [-1910.2, 18,098.8] at 1 month after vaccination, and 1764.1 [-4133.9, 7662.1] at 2 months after vaccination in the adjusted models). Conclusion: The findings suggest that the presence of fever after the third vaccine does not predict a sustained elevation in serum antibody titers. © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases
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Highly mutable pathogens pose daunting challenges for antibody design. The usual criteria of high potency and specificity are often insufficient to design antibodies that provide long-lasting protection. This is due, in part, to the ability of the pathogen to rapidly acquire mutations that permit them to evade the designed antibodies. To overcome these limitations, design of antibodies with a larger neutralizing breadth can be pursued. Such broadly neutralizing antibodies (bnAbs) should remain targeted to a specific epitope, yet show robustness against pathogen mutability, thereby neutralizing a higher number of antigens. This is particularly important for highly mutable pathogens, like the influenza virus and the human immunodeficiency virus (HIV). The protocol describes a method for computing the "breadth” of a given antibody, an essential aspect of antibody design. © 2023, Springer Science+Business Media, LLC, part of Springer Nature.
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Purpose: We examined a positivity of corona virus antibody in kidney transplant recipients who received two-doses BNT162B2 (mRNA) vaccination during the beginning 6 months in 2021. Method(s): The subjects include 111 kidney transplant recipients who received two-doses BNT162B2 (mRNA) vaccination, consisting of 61 male and 50 females, 53.7+/-14.7 years old on average. Healthy 10 volunteers were also enrolled in this study as a control group. We adopted LABScreen COVID plus beads (One Lambda) as an antibody reagent to detect antibodies against corona viruses including 5 types structural proteins such as extracellular domain (ECD), Spike 1, Spike 2, receptorbinding domain (RBD) and nucleoside. Result(s): Among 111 recipients, 46 recipients showed positivity (41%), whilst all control showed positivity (100%). Among 100 recipients taking tacrolimus, 37 recipients showed positivity, although 9 recipients out of 10 taking cyclosporine showed positivity (90%). It is noteworthy that recipients receiving rituximab (CD20 antibody) significantly shows lower rate of antibody positivity. The period between vaccination and rituximab administration is closely related to the positivity of antibody positivity. In recipients without rituximab administration, lower trough level for tacrolimus and MMF is related to higher positivity of antibody production. Positivity pattern in 5 protein fragments shows individually various different in transplant recipients, while it shows stable pattern in healthy volunteers. Conclusion(s): Kidney transplant recipients showed lower positivity of corona virus antibody compared to healthy volunteers, which is deeply related to immunosuppression in the past. This assay in this study yields reproductive excellent results for corona virus antibody. The assay helps us to find the appropriate booster vaccination time and doses on the basis of these past results. (Figure Presented).