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1.
Infect Drug Resist ; 15: 4127-4136, 2022.
Article in English | MEDLINE | ID: covidwho-1974458

ABSTRACT

Purpose: This study was conducted to investigate antibody immune responses induced by BNT162b2 and AZD1222 human COVID-19 vaccines in Riyadh city, Saudi Arabia. Patients and Methods: ELISA was used to evaluate antibodies, against the SARS-CoV-2 spike S1 protein, in serum samples from 432 vaccinated individuals at six time points: pre-vaccination (baseline), post-prime, post-boost, 6-months, and 1 year post-vaccination, and 3 weeks post a third dose. Virus microneutralization assay was used to confirm antibody responses in a subset of samples. Results: Anti-SARS-CoV-2 spike IgG were detected in most subjects post-prime, reached a peak level post-boost, and remained at high level at the 6-month follow-up. At 1 year post-vaccine, the antibody levels were low but increased to a significant level higher than the peak following a third dose. The third dose was given at an average of 250 days after the second dose. The virus microneutralization assay confirmed the neutralization activity of the induced SARS-CoV-2 IgG antibodies. The vaccines induced higher IgG titres at post-prime (p=0.0001) and 6 months (p=0.006) in previously infected individuals. An increased interval between prime and boost, more than recommended time, appeared to enhance the IgG levels (p=0004). Moreover, the vaccines induced higher IgG levels in younger subjects (p=0.01). Conclusion: These data provide insights and build on the current understanding of immune responses induced by these two vaccines; and support a third boosting dose for these COVID-19 vaccines.

2.
Trends Immunol ; 43(8): 640-656, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1972143

ABSTRACT

Tuberculosis (TB), the world's deadliest bacterial infection, afflicts more human males than females, with a male/female (M/F) ratio of 1.7. Sex disparities in TB prevalence, pathophysiology, and clinical manifestations are widely reported, but the underlying biological mechanisms remain largely undefined. This review assesses epidemiological data on sex disparity in TB, as well as possible underlying hormonal and genetic mechanisms that might differentially modulate innate and adaptive immune responses in males and females, leading to sex differences in disease susceptibility. We consider whether this sex disparity can be extended to the efficacy of vaccines and discuss novel animal models which may offer mechanistic insights. A better understanding of the biological factors underpinning sex-related immune responses in TB may enable sex-specific personalized therapies for TB.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis , Animals , Disease Susceptibility , Female , Humans , Immunity , Male , Tuberculosis/genetics
3.
Cell Rep ; : 111214, 2022 Aug 03.
Article in English | MEDLINE | ID: covidwho-1966424

ABSTRACT

Vaccine-associated enhanced respiratory disease (VAERD) is a severe complication for some respiratory infections. To investigate the potential for VAERD induction in coronavirus disease 2019 (COVID-19), we evaluate two vaccine leads utilizing a severe hamster infection model: a T helper type 1 (TH1)-biased measles vaccine-derived candidate and a TH2-biased alum-adjuvanted, non-stabilized spike protein. The measles virus (MeV)-derived vaccine protects the animals, but the protein lead induces VAERD, which can be alleviated by dexamethasone treatment. Bulk transcriptomic analysis reveals that our protein vaccine prepares enhanced host gene dysregulation in the lung, exclusively up-regulating mRNAs encoding the eosinophil attractant CCL-11, TH2-driving interleukin (IL)-19, or TH2 cytokines IL-4, IL-5, and IL-13. Single-cell RNA sequencing (scRNA-seq) identifies lung macrophages or lymphoid cells as sources, respectively. Our findings imply that VAERD is caused by the concerted action of hyperstimulated macrophages and TH2 cytokine-secreting lymphoid cells and potentially links VAERD to antibody-dependent enhancement (ADE). In summary, we identify the cytokine drivers and cellular contributors that mediate VAERD after TH2-biased vaccination.

4.
Clin Chim Acta ; 532: 130-136, 2022 Jul 01.
Article in English | MEDLINE | ID: covidwho-1966414

ABSTRACT

Both infection with and vaccination against SARS-CoV-2 trigger a complex B-cell and T-cell response. Methods for the analysis of the B-cell response are now well established. However, reliable methods for measuring the T-cell response are less well established and their usefulness in clinical settings still needs to be proven. Here, we have developed and validated a T-cell proliferation assay based on 3H thymidine incorporation. The assay is using SARS-CoV-2 derived peptide pools that cover the spike (S), the nucleocapsid (N) and the membrane (M) protein for stimulation. We have compared this novel SARS-CoV-2 lymphocyte transformation test (SARS-CoV-2 LTT) to an established ELISA assay detecting Immunoglobulin G (IgG) antibodies to the S1 subunit of the SARS-CoV-2 spike protein. The study was carried out using blood samples from both vaccinated and infected health care workers as well as from a non-infected control group. Our novel SARS-CoV-2 LTT shows excellent discrimination of infected and/or vaccinated individuals versus unexposed controls, with the ROC analysis showing an area under the curve (AUC) of > 0.95. No false positives were recorded as all unexposed controls had a negative LTT result. When using peptide pools not only representing the S protein (found in all currently approved vaccines) but also the N and M proteins (not contained in the vast majority of vaccines), the novel SARS-CoV-2 LTT can also discriminate T-cell responses resulting from vaccination against those induced by infection.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19/diagnosis , Cell Proliferation , Humans , Peptides , Spike Glycoprotein, Coronavirus , T-Lymphocytes , Vaccination
6.
Vaccines (Basel) ; 10(8)2022 Jul 25.
Article in English | MEDLINE | ID: covidwho-1957472

ABSTRACT

The COVID-19 pandemic is entering a new era with the approval of many SARS-CoV-2 vaccines. In spite of the restoration of an almost normal way of life thanks to the immune protection elicited by these innovative vaccines, we are still facing high viral circulation, with a significant number of deaths. To further explore alternative vaccination platforms, we developed COVID-eVax-a genetic vaccine based on plasmid DNA encoding the RBD domain of the SARS-CoV-2 spike protein. Here, we describe the correlation between immune responses and the evolution of viral infection in ferrets infected with the live virus. We demonstrate COVID-eVax immunogenicity as means of antibody response and, above all, a significant T-cell response, thus proving the critical role of T-cell immunity, in addition to the neutralizing antibody activity, in controlling viral spread.

7.
Cell Biosci ; 12(1): 88, 2022 Jun 11.
Article in English | MEDLINE | ID: covidwho-1957070

ABSTRACT

BACKGROUND: An animal model that can mimic the SARS-CoV-2 infection in humans is critical to understanding the rapidly evolving SARS-CoV-2 virus and for development of prophylactic and therapeutic strategies to combat emerging mutants. Studies show that the spike proteins of SARS-CoV and SARS-CoV-2 bind to human angiotensin-converting enzyme 2 (hACE2, a well-recognized, functional receptor for SARS-CoV and SARS-CoV-2) to mediate viral entry. Several hACE2 transgenic (hACE2Tg) mouse models are being widely used, which are clearly invaluable. However, the hACE2Tg mouse model cannot fully explain: (1) low expression of ACE2 observed in human lung and heart, but lung or heart failure occurs frequently in severe COVID-19 patients; (2) low expression of ACE2 on immune cells, but lymphocytopenia occurs frequently in COVID-19 patients; and (3) hACE2Tg mice do not mimic the natural course of SARS-CoV-2 infection in humans. Moreover, one of most outstanding features of coronavirus infection is the diversity of receptor usage, which includes the newly proposed human CD147 (hCD147) as a possible co-receptor for SARS-CoV-2 entry. It is still debatable whether CD147 can serve as a functional receptor for SARS-CoV-2 infection or entry. RESULTS: Here we successfully generated a hCD147 knock-in mouse model (hCD147KI) in the NOD-scid IL2Rgammanull (NSG) background. In this hCD147KI-NSG mouse model, the hCD147 genetic sequence was placed downstream of the endogenous mouse promoter for mouse CD147 (mCD147), which creates an in vivo model that may better recapitulate physiological expression of hCD147 proteins at the molecular level compared to the existing and well-studied K18-hACE2-B6 (JAX) model. In addition, the hCD147KI-NSG mouse model allows further study of SARS-CoV-2 in the immunodeficiency condition which may assist our understanding of this virus in the context of high-risk populations in immunosuppressed states. Our data show (1) the human CD147 protein is expressed in various organs (including bronchiolar epithelial cells) in hCD147KI-NSG mice by immunohistochemical staining and flow cytometry; (2) hCD147KI-NSG mice are marginally sensitive to SARS-CoV-2 infection compared to WT-NSG littermates characterized by increased viral copies by qRT-PCR and moderate body weight decline compared to baseline; (3) a significant increase in leukocytes in the lungs of hCD147KI-NSG mice, compared to infected WT-NSG mice. CONCLUSIONS: hCD147KI-NSG mice are more sensitive to COVID-19 infection compared to WT-NSG mice. The hCD147KI-NSG mouse model can serve as an additional animal model for further interrogation whether CD147 serve as an independent functional receptor or accessory receptor for SARS-CoV-2 entry and immune responses.

8.
J Med Virol ; 2022 Jun 15.
Article in English | MEDLINE | ID: covidwho-1941180

ABSTRACT

The virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the global coronavirus disease-2019 (COVID-19) pandemic, spread rapidly around the world causing high morbidity and mortality. However, there are four known, endemic seasonal coronaviruses in humans (HCoVs), and whether antibodies for these HCoVs play a role in severity of COVID-19 disease has generated a lot of interest. Of these seasonal viruses NL63 is of particular interest as it uses the same cell entry receptor as SARS-CoV-2. We use functional, neutralizing assays to investigate cross-reactive antibodies and their relationship with COVID-19 severity. We analyzed the neutralization of SARS-CoV-2, NL63, HKU1, and 229E in 38 COVID-19 patients and 62 healthcare workers, and a further 182 samples to specifically study the relationship between SARS-CoV-2 and NL63. We found that although HCoV neutralization was very common there was little evidence that these antibodies neutralized SARS-CoV-2. Despite no evidence in cross-neutralization, levels of NL63 neutralizing antibodies become elevated after exposure to SARS-CoV-2 through infection or following vaccination.

9.
Int J Environ Res Public Health ; 19(13)2022 07 02.
Article in English | MEDLINE | ID: covidwho-1934069

ABSTRACT

Exercise training involving exercises of optimal intensity and duration improves psychological and medical variables in relative leisure-deprived people living with HIV/AIDS. This study aimed to analyze associated psychological variables and the effect of exercise intensity and duration on immune responses in relative leisure-deprived people infected with HIV. The participants completed different moderate-intensity exercises (30 min (60-80% HRmax) and 45 min (60-80% HRmax)) and high-intensity exercise for 10 min (>80% HRmax). Levels higher than "normal" were rated for relative leisure deprivation, indicating relative deprivation of leisure among participants. The overall level of quality of life was "normal", indicating that quality of life was not considered high. The stress level was psychologically considered low. Time had a significant effect on cortisol levels (p < 0.05). Compared to pre-exercise, cortisol level was significantly decreased immediately after moderate exercise for 45 min and 3 h post-exercise after high-intensity exercise for 10 min (p < 0.05). However, time and the interaction of condition and time had no significant effect on IL-6 and sIgA levels (p > 0.05). Despite the small sample size of this pilot study, the results demonstrate that moderate-intensity exercise can be recommended to improve the health and quality of life of people infected with HIV.


Subject(s)
Acquired Immunodeficiency Syndrome , Hydrocortisone , Exercise , Humans , Immunity , Leisure Activities , Pilot Projects
10.
Front Immunol ; 13: 868361, 2022.
Article in English | MEDLINE | ID: covidwho-1933649

ABSTRACT

Background: Residents of nursing homes are one of the most vulnerable groups during the severe acute syndrome coronavirus 2 (SARS-CoV-2) pandemic. The aim of this study was to characterize cellular and humoral immune responses in >70-year-old participants before vaccination, after first and second vaccination with BNT162b2, in contrast to second-dose-vaccinated participants younger than 60 years. Methods: Peripheral blood mononuclear cells of 45 elderly and 40 younger vaccinees were analyzed by IFNγ ELISpot, specific immunoglobulin G antibody titers against SARS-CoV-2 spike protein, and neutralization abilities against SARS-CoV-2 wild-type (WT) and Delta variant (B.1.617.2). Results: Our results clearly demonstrate a significantly increased T cell response, IgG titers, and neutralization activities against SARS-CoV-2 WT and Delta between first and second vaccination with BNT162b2 in elderly vaccinees, thereby highlighting the importance of the second booster. Interestingly, similar cellular and humoral immune responses against SARS-CoV-2 WT and Delta were found after the second vaccine dose in the young and elderly groups. Conclusions: Our data demonstrate a full picture of cellular and humoral immune responses of BNT162b2-vaccinees in two age cohorts. In all vaccines, SARS-CoV-2 WT-specific antibodies with similar neutralizing activity were detected in all vaccinees. After the second vaccination, neutralization titers against SARS-CoV-2 Delta were impaired in both age groups compared with SARS-CoV-2 WT, thereby emphasizing the need for an additional booster to overcome rising variants of SARS-CoV-2.


Subject(s)
COVID-19 , Viral Vaccines , Aged , Antibodies, Viral , BNT162 Vaccine , Humans , Immunity, Humoral , Leukocytes, Mononuclear , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
11.
Acta Pharmaceutica Sinica B ; 12(5):2206-2223, 2022.
Article in English | Web of Science | ID: covidwho-1926204

ABSTRACT

Looking retrospectively at the development of humanity, vaccination is an unprecedented medical landmark that saves lives by harnessing the human immune system. During the ongoing coronavirus disease 2019 (COVID-19) pandemic, vaccination is still the most effective defense modality. The successful clinical application of the lipid nanoparticle-based Pfizer/BioNTech and Moderna mRNA COVID-19 vaccines highlights promising future of nanotechnology in vaccine development. Compared with conventional vaccines, nanovaccines are supposed to have advantages in lymph node accumulation, antigen assembly, and antigen presentation;they also have, unique pathogen biomimicry properties because of well-organized combination of multiple immune factors. Beyond infectious diseases, vaccine nanotechnology also exhibits considerable potential for cancer treatment. The ultimate goal of cancer vaccines is to fully mobilize the potency of the immune system as a living therapeutic to recognize tumor antigens and eliminate tumor cells, and nanotechnologies have the requisite properties to realize this goal. In this review, we summarize the recent advances in vaccine nanotechnology from infectious disease prevention to cancer immunotherapy and highlight the different types of materials, mechanisms, administration methods, as well as future perspectives. (C) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

12.
Front Immunol ; 13: 873195, 2022.
Article in English | MEDLINE | ID: covidwho-1911041

ABSTRACT

COVID-19 has proven to be particularly serious and life-threatening for patients presenting with pre-existing pathologies. Patients affected by rheumatic musculoskeletal disease (RMD) are likely to have impaired immune responses against SARS-CoV-2 infection due to their compromised immune system and the prolonged use of disease-modifying anti-rheumatic drugs (DMARDs), which include conventional synthetic (cs) DMARDs or biologic and targeted synthetic (b/ts) DMARDs. To provide an integrated analysis of the immune response following SARS-CoV-2 infection in RMD patients treated with different classes of DMARDs we carried out an immunological analysis of the antibody responses toward SARS-CoV-2 nucleocapsid and RBD proteins and an extensive immunophenotypic analysis of the major immune cell populations. We showed that RMD individuals under most DMARD treatments mount a sustained antibody response to the virus, with neutralizing activity. In addition, they displayed a sizable percentage of effector T and B lymphocytes. Among b-DMARDs, we found that anti-TNFα treatments are more favorable drugs to elicit humoral and cellular immune responses as compared to CTLA4-Ig and anti-IL6R inhibitors. This study provides a whole picture of the humoral and cellular immune responses in RMD patients by reassuring the use of DMARD treatments during COVID-19. The study points to TNF-α inhibitors as those DMARDs permitting elicitation of functional antibodies to SARS-CoV-2 and adaptive effector populations available to counteract possible re-infections.


Subject(s)
Antirheumatic Agents , COVID-19 , Rheumatic Diseases , Antirheumatic Agents/therapeutic use , COVID-19/drug therapy , Humans , Immunosuppressive Agents/therapeutic use , Rheumatic Diseases/drug therapy , SARS-CoV-2
13.
Cell Rep ; 39(13): 110989, 2022 Jun 28.
Article in English | MEDLINE | ID: covidwho-1906847

ABSTRACT

The interleukin-12 (IL-12) family comprises the only heterodimeric cytokines mediating diverse functional effects. We previously reported a striking bimodal IL-12p70 response to lipopolysaccharide (LPS) stimulation in healthy donors. Herein, we demonstrate that interferon ß (IFNß) is a major upstream determinant of IL-12p70 production, which is also associated with numbers and activation of circulating monocytes. Integrative modeling of proteomic, genetic, epigenomic, and cellular data confirms IFNß as key for LPS-induced IL-12p70 and allowed us to compare the relative effects of each of these parameters on variable cytokine responses. Clinical relevance of our findings is supported by reduced IFNß-IL-12p70 responses in patients hospitalized with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or chronically infected with hepatitis C (HCV). Importantly, these responses are resolved after viral clearance. Our systems immunology approach defines a better understanding of IL-12p70 and IFNß in healthy and infected persons, providing insights into how common genetic and epigenetic variation may impact immune responses to bacterial infection.


Subject(s)
Interferon-beta , Interleukin-12 , Toll-Like Receptor 4 , COVID-19/immunology , COVID-19/metabolism , COVID-19/virology , Cytokines/immunology , Cytokines/metabolism , Humans , Interferon-beta/immunology , Interferon-beta/metabolism , Interleukin-12/immunology , Interleukin-12/metabolism , Lipopolysaccharides/pharmacology , Proteomics , SARS-CoV-2/immunology
14.
Virulence ; 13(1): 1076-1087, 2022 12.
Article in English | MEDLINE | ID: covidwho-1908665

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has affected millions of individuals with various implications. Consistent with the crucial role of the microbiome in determining health and disease in humans, various studies have investigated the gut and respiratory microbiome effect on the COVID-19. Microbiota dysbiosis might support the entry, replication, and establishment of SARS-CoV-2 infection by modulating various mechanisms. One of the main mechanisms that the modulation of respiratory microbiota composition during the COVID-19 infection affects the magnitude of the disease is changes in innate and acquired immune responses, including inflammatory markers and cytokines and B- and T-cells. The diversity of respiratory microbiota in COVID-19 patients is controversial; some studies reported low microbial diversity, while others found high diversity, suggesting the role of respiratory microbiota in this disease. Modulating microbiota diversity and profile by supplementations and nutrients can be applied prophylactic and therapeutic in combating COVID-19. Here, we discussed the lung microbiome dysbiosis during various lung diseases and its interaction with immune cells, focusing on COVID-19.


Subject(s)
COVID-19 , Microbiota , Dysbiosis , Humans , Lung , SARS-CoV-2
15.
Front Immunol ; 13: 890517, 2022.
Article in English | MEDLINE | ID: covidwho-1903021

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated symptoms, named coronavirus disease 2019 (COVID-19), have rapidly spread worldwide, resulting in the declaration of a pandemic. When several countries began enacting quarantine and lockdown policies, the pandemic as it is now known truly began. While most patients have minimal symptoms, approximately 20% of verified subjects are suffering from serious medical consequences. Co-existing diseases, such as cardiovascular disease, cancer, diabetes, and others, have been shown to make patients more vulnerable to severe outcomes from COVID-19 by modulating host-viral interactions and immune responses, causing severe infection and mortality. In this review, we outline the putative signaling pathways at the interface of COVID-19 and several diseases, emphasizing the clinical and molecular implications of concurring diseases in COVID-19 clinical outcomes. As evidence is limited on co-existing diseases and COVID-19, most findings are preliminary, and further research is required for optimal management of patients with comorbidities.


Subject(s)
COVID-19 , COVID-19/epidemiology , Communicable Disease Control , Humans , Pandemics , Quarantine , SARS-CoV-2
16.
Iran J Basic Med Sci ; 25(5): 554-561, 2022 May.
Article in English | MEDLINE | ID: covidwho-1897274

ABSTRACT

Objectives: SARS-CoV-2, emerging as a major threat to public health, has to be controlled through vaccination. Naloxone (NLX), an opioid receptor antagonist, demonstrated its adjuvant activity for microbial vaccines. In this study, inactivated SARS-CoV-2 was developed in the Alum/NLX adjuvant to increase the potency of the inactivated SARS-CoV-2 vaccine. Materials and Methods: BALB/c mice were immunized on days 0 and 14 with inactivated SARS-CoV-2-Alum, -Alum + NLX 3 mg/kg, -Alum + NLX 10 mg/kg, and -Freund adjuvant, as well as PBS. IFN-γ and IL-4 cytokines and Granzyme-B release were assessed with ELISA. In addition, specific total IgG, IgG1/IgG2a isotypes, and ratio as well as anti-RBD IgG responses were assessed with an optimized ELISA. Results: SARS-CoV-2-Alum-NLX10 group showed a significant increase in the IFN-γ cytokine response versus SARS-CoV-2-Alum, SARS-CoV-2-Alum-NLX3, and PBS groups. The SARS-CoV-2-Alum-NLX3 group exhibited a significant decrease in IL-4 cytokine versus SARS-CoV-2-Alum. The mice immunized with SARS-CoV-2-Alum-NLX10 showed a significant increase in CTL activity versus SARS-CoV-2-Alum and PBS. In addition, mice immunized with SARS-CoV-2-Alum-NLX3, SARS-CoV-2-Alum-NLX10 and SARS-CoV-2-Freund demonstrated an increase in IgG response, as compared with SARS-CoV-2-Alum and PBS group. Furthermore, all formulations of SARS-CoV-2 vaccines could induce both IgG1 and IgG2a isotypes. But, the IgG2a/IgG1 ratio in SARS-CoV-2-Freund and SARS-CoV-2-Alum-NLX10 revealed an increase as compared with that of the SARS-CoV-2-Alum group. Anti-RBD IgG response in the SARS-CoV-2-Alum-NLX10 group showed a significant increase as compared with the Alum-based vaccine. Conclusion: Formulation of inactivated SARS-CoV-2 virus in NLX/alum adjuvant improved the potency of humoral and, especially, cellular responses.

17.
Infect Drug Resist ; 15: 2469-2474, 2022.
Article in English | MEDLINE | ID: covidwho-1896594

ABSTRACT

Purpose: To evaluate the response and safety of an inactivated vaccine (Sinovac Life Sciences Co., Ltd., Beijing, China) for coronavirus disease 2019 (COVID-19) in liver transplant (LTx) recipients from China. Patients and Methods: Thirty-five recipients post LTx from the First Affiliated Hospital of Zhejiang University School of Medicine who received inactivated vaccine from June to October 2021 were screened. Information regarding vaccine side effects and clinical data were collected. Results: Thirty-five LTx recipients were enrolled, with a mean age of 46 years, and most patients were male (30, 85.71%). All the participants had a negative history of COVID-19 infection. Predictors for negative response in the recipients were interleukin-2 receptor (IL-2R) induction during LTx, shorter time post LTx and application of a derivative from mycophenolate acid (MPA). No serious adverse events were observed during the progress of vaccination or after the vaccination. Conclusion: LTx recipients have a substantially partial immunological response to the inactivated vaccine for COVID-19. IL-2R induction during LTx, a shorter time post LTx and the application of a derivative from MPA seem to be predictors for a negative serological immunoglobulin G (IgG) antibody response in recipients. The findings require booster vaccination in these LTx recipients.

18.
Front Immunol ; 13: 889138, 2022.
Article in English | MEDLINE | ID: covidwho-1875415

ABSTRACT

Background: Individuals with secondary immunodeficiencies belong to the most vulnerable groups to succumb to COVID-19 and thus are prioritized for SARS-CoV-2 vaccination. However, knowledge about the persistence and anamnestic responses following SARS-CoV-2-mRNA vaccinations is limited in these patients. Methods: In a prospective, open-label, phase four trial we analyzed S1-specific IgG, neutralizing antibodies and cytokine responses in previously non-infected patients with cancer or autoimmune disease during primary mRNA vaccination and up to one month after booster. Results: 263 patients with solid tumors (SOT, n=63), multiple myeloma (MM, n=70), inflammatory bowel diseases (IBD, n=130) and 66 controls were analyzed. One month after the two-dose primary vaccination the highest non-responder rate was associated with lower CD19+ B-cell counts and was found in MM patients (17%). S1-specific IgG levels correlated with IL-2 and IFN-γ responses in controls and IBD patients, but not in cancer patients. Six months after the second dose, 18% of patients with MM, 10% with SOT and 4% with IBD became seronegative; no one from the control group became negative. However, in IBD patients treated with TNF-α inhibitors, antibody levels declined more rapidly than in controls. Overall, vaccination with mRNA-1273 led to higher antibody levels than with BNT162b2. Importantly, booster vaccination increased antibody levels >8-fold in seroresponders and induced anamnestic responses even in those with undetectable pre-booster antibody levels. Nevertheless, in IBD patients with TNF-α inhibitors even after booster vaccination, antibody levels were lower than in untreated IBD patients and controls. Conclusion: Immunomonitoring of vaccine-specific antibody and cellular responses seems advisable to identify vaccination failures and consequently establishing personalized vaccination schedules, including shorter booster intervals, and helps to improve vaccine effectiveness in all patients with secondary immunodeficiencies. Trial registration: EudraCT Number: 2021-000291-11.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , Multiple Myeloma , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunization, Secondary , Immunocompromised Host , Immunoglobulin G , Immunologic Memory , Multiple Myeloma/therapy , Prospective Studies , RNA, Messenger , SARS-CoV-2 , Tumor Necrosis Factor-alpha , Vaccination
19.
J Med Virol ; 2022 Jun 02.
Article in English | MEDLINE | ID: covidwho-1872246

ABSTRACT

The coronavirus disease-19 (COVID-19) pandemic became the greatest public health challenge globally. In our study, it was aimed to determine the antibody levels in the third month after the COVID-19 infection and the symptoms that continued until the third month from the onset of the infection. One hundred people who applied to Tarsus State Hospital with the suspicion of COVID-19 and were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by real-time reverse transcriptase-polymerase chain reaction were included. We collected serum samples from individuals, who were 3 months postinfection, and tested them in anti-SARS-CoV-2 Quanti-Vac ELISA IgG kit coated with recombinant S1 antigen for testing SARS-CoV-2 antibodies. Antibody levels were found to be higher in those aged ≥55 years, nonsmokers, those with comorbidities, and those who were hospitalized. The four most common symptoms that individuals initially encounter; are weakness, muscle and joint pain, loss of taste and smell, and cough. In 3 months after COVID-19 infection, the most common four symptoms are; muscle and joint pain, insomnia, fatigue, and other problems were determined. In conclusion; more research is needed to determine threshold levels of serum antibodies that could prevent reinfection of SARS-CoV-2.

20.
Mol Divers ; 2022 May 26.
Article in English | MEDLINE | ID: covidwho-1864434

ABSTRACT

SARS, or severe acute respiratory syndrome, is caused by a novel coronavirus (COVID-19). This situation has compelled many pharmaceutical R&D companies and public health research sectors to focus their efforts on developing effective therapeutics. SARS-nCoV-2 was chosen as a protein spike to targeted monoclonal antibodies and therapeutics for prevention and treatment. Deep mutational scanning created a monoclonal antibody to characterize the effects of mutations in a variable antibody fragment based on its expression levels, specificity, stability, and affinity for specific antigenic conserved epitopes to the Spike-S-Receptor Binding Domain (RBD). Improved contacts between Fv light and heavy chains and the targeted antigens of RBD could result in a highly potent neutralizing antibody (NAbs) response as well as cross-protection against other SARS-nCoV-2 strains. It undergoes multipoint core mutations that combine enhancing mutations, resulting in increased binding affinity and significantly increased stability between RBD and antibody. In addition, we improved. Structures of variable fragment (Fv) complexed with the RBD of Spike protein were subjected to our established in-silico antibody-engineering platform to obtain enhanced binding affinity to SARS-nCoV-2 and develop ability profiling. We found that the size and three-dimensional shape of epitopes significantly impacted the activity of antibodies produced against the RBD of Spike protein. Overall, because of the conformational changes between RBD and hACE2, it prevents viral entry. As a result of this in-silico study, the designed antibody can be used as a promising therapeutic strategy to treat COVID-19.

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