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Virologica Sinica Jun 2021Successful vaccines induce specific immune responses and protect against various viral and bacterial infections. Noninactivated vaccines, especially viral vector...
Successful vaccines induce specific immune responses and protect against various viral and bacterial infections. Noninactivated vaccines, especially viral vector vaccines such as adenovirus and poxvirus vaccines, dominate the vaccine market because their viral particles are able to replicate and proliferate in vivo and produce lasting immunity in a manner similar to natural infection. One challenge of human and livestock vaccination is vaccine stability related to the antigenicity and infectivity. Freeze-drying is the typical method to maintain virus vaccine stability, while cold chain transportation is required for temperatures about 2 °C-8 °C. The financial and technological resource requirements hinder vaccine distribution in underdeveloped areas. In this study, we developed a freeze-drying formula consisting of bovine serum albumin (BSA), L-glutamic acid (L-Glu), polyethylene glycol (PEG), and dextran (DEX) to improve the thermal stability and activity of viral vaccines, including vaccinia recombinant vaccine (rTTV-OVA) and adenovirus vaccine (Ad5-ENV). We compared a panel of five different formulations (PEG: DEX: BSA: L-GLU = 50:9:0:0(#1), 50:5:4:0(#2), 50:10:9:0(#3), 50:0:0:9(#4), and 50:1:0:8(#5), respectively) and optimized the freeze-drying formula for rTTV-OVA and Ad5-ENV. We found that the freeze-drying formulations #2 and #3 could maintain rTTV-OVA infectivity at temperatures of 4 °C and 25 °C and that rTTV-OVA immunogenicity was retained during lyophilization. However, formulations #4 and #5 maintained Ad5-ENV infectivity under the same conditions, and Ad5-ENV immunogenicity had maximum retention with freeze-drying formulation #4. In summary, we developed new freeze-drying formulations that increased virus vaccine storage times and retained immunogenicity at an ambient temperature.
Topics: Adenoviridae; Adenovirus Vaccines; Drug Stability; Freeze Drying; Humans; Temperature
PubMed: 32696399
DOI: 10.1007/s12250-020-00250-1 -
Thrombosis Research Dec 2021Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare coagulation disorder reported after administration of COVID-19 adenovirus-vectored vaccines. VITT is...
BACKGROUND
Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare coagulation disorder reported after administration of COVID-19 adenovirus-vectored vaccines. VITT is mediated by anti-platelet factor 4 (PF4) antibodies activating platelets through the Fcγ-receptor II (FcγRII), and it is associated with strong fibrin turnover. The complement system is involved in several other immunothrombotic entities, but its impact on VITT is not established.
OBJECTIVE
To assess antibodies in interaction with the activation of platelets and complement triggered by VITT.
METHODS
Antibodies against adenovirus type 2 hexon protein, ChAdOx1 adenoviral vector-specific IgG and PF4 were analyzed by enzyme immunoassays from VITT patients (n = 5). The EDTA plasma samples of the patients and controls were used to measure both terminal complement complexes (TCC) by ELISA and aggregation of healthy donor platelets. We studied the effects of human immunoglobulin (IVIG) and glycoprotein IIb/IIIa inhibitor (GPIIb/IIIa) on spontaneous and collagen-induced platelet aggregation supplemented with VITT plasma.
RESULTS
None of the patients had experienced a COVID-19 infection. Antibody analyses confirmed the immunogenicity of the adenovirus-vectored ChAdOx1 vaccine. Moreover, VITT plasma had anti-PF4 antibodies and elevated TCC levels as a sign of complement activation. In isolated healthy donor platelets, VITT patient plasma caused marked, spontaneous aggregation of platelets, which was abolished by eptifibatide and high-dose therapeutic IVIG.
CONCLUSIONS
Our findings suggest that VITT is triggered by antibodies against adenovirus vector and PF4-polyanion complexes which strongly co-activate complement and platelets. The spontaneous platelet aggregation was suppressed by IVIG or eptifibatide, indicating that besides FcγRII, also GPIIb/IIIa receptor exerts platelet procoagulant role in VITT.
Topics: Adenoviridae; Adenovirus Vaccines; Blood Platelets; COVID-19; COVID-19 Vaccines; Humans; Immunoglobulin G; Platelet Factor 4; SARS-CoV-2
PubMed: 34768097
DOI: 10.1016/j.thromres.2021.10.027 -
Journal of Medical Virology Dec 2021To systematically evaluate the effectiveness and safety of the SARS-CoV-2 vaccines currently undergoing clinical trials. (Review)
Review Meta-Analysis
OBJECTIVE
To systematically evaluate the effectiveness and safety of the SARS-CoV-2 vaccines currently undergoing clinical trials.
METHODS
PubMed, EMBASE, and Cochrane Library databases were searched to collect open human COVID-19 vaccines randomized controlled trials, without limiting the search time and language. The research papers collected in the above-mentioned databases were initially screened according to the title and abstract content and merged, and the repeated ones were removed. After reading the full text of the remaining research, the studies that did not meet the inclusion criteria were excluded, and finally, nine studies were obtained. After extracting the statistical data of adverse events in the study, load them into Review Manager for heterogeneity analysis.
RESULTS
The incidence of adverse reactions of inactivated virus vaccines, RNA vaccines, and adenovirus vector vaccines was higher than that of placebo. Common adverse reactions included pain, swelling, and fever at the injection site.
CONCLUSION
From the perspective of effectiveness, RNA vaccine > adenovirus vector vaccine > inactivated virus vaccine. From the perspective of safety, the incidence of adverse reactions of the three vaccines is higher than that of a placebo, and the incidence of adverse reactions of the adenovirus vector vaccine is higher.
Topics: Adenovirus Vaccines; COVID-19; COVID-19 Vaccines; Humans; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Vaccination; Vaccines, Inactivated; Vaccines, Synthetic
PubMed: 34264528
DOI: 10.1002/jmv.27203 -
Clinical Infectious Diseases : An... Apr 2023While rotavirus causes severe diarrheal disease in children aged <5 years, data on other viral causes in sub-Saharan Africa are limited.
Prevalence, Clinical Severity, and Seasonality of Adenovirus 40/41, Astrovirus, Sapovirus, and Rotavirus Among Young Children With Moderate-to-Severe Diarrhea: Results From the Vaccine Impact on Diarrhea in Africa (VIDA) Study.
BACKGROUND
While rotavirus causes severe diarrheal disease in children aged <5 years, data on other viral causes in sub-Saharan Africa are limited.
METHODS
In the Vaccine Impact on Diarrhea in Africa study (2015-2018), we analyzed stool from children aged 0-59 months with moderate-to-severe diarrhea (MSD) and without diarrhea (controls) in Kenya, Mali, and The Gambia using quantitative polymerase chain reaction. We derived the attributable fraction (AFe) based on the association between MSD and the pathogen, accounting for other pathogens, site, and age. A pathogen was attributable if the AFe was ≥0.5.The severity of attributable MSD was defined by a modified Vesikari score (mVS). Monthly cases were plotted against temperature and rainfall to assess seasonality.
RESULTS
Among 4840 MSD cases, proportions attributed to rotavirus, adenovirus 40/41, astrovirus, and sapovirus were 12.6%, 2.7%, 2.9%, and 1.9%, respectively. Attributable rotavirus, adenovirus 40/41, and astrovirus MSD cases occurred at all sites, with mVS of 11, 10, and 7, respectively. MSD cases attributable to sapovirus occurred in Kenya, with mVS of 9. Astrovirus and adenovirus 40/41 peaked during the rainy season in The Gambia, while rotavirus peaked during the dry season in Mali and The Gambia.
CONCLUSIONS
In sub-Saharan Africa, rotavirus was the most common cause of MSD; adenovirus 40/41, astrovirus, and sapovirus contributed to a lesser extent among children aged <5 years. Rotavirus- and adenovirus 40/41-attributable MSD were most severe. Seasonality varied by pathogen and location. Efforts to increase the coverage of rotavirus vaccines and to improve prevention and treatment for childhood diarrhea should continue.
Topics: Child; Humans; Infant; Child, Preschool; Rotavirus; Sapovirus; Prevalence; Diarrhea; Adenoviridae; RNA Viruses; Kenya; Feces; Vaccines
PubMed: 37074439
DOI: 10.1093/cid/ciad060 -
Medicina 2021The BCG vaccine was given for the first time in 1921, in Paris, to a newborn of a mother with tuberculosis. Between 1924 and 1960, the Pasteur Institute delivered BCG...
The BCG vaccine was given for the first time in 1921, in Paris, to a newborn of a mother with tuberculosis. Between 1924 and 1960, the Pasteur Institute delivered BCG cultures to more than 50 laboratories around the world. In 1925, Dr Andrés Arena introduced the BCG seed to Argentina, where the vaccine began to be produced and applied orally to newborns. The original strain underwent diverse genetic changes in different parts of the world, which did not seem to affect its protective efficacy. In Argentina, a study (1978-1985) showed that BCG prevents primary TB in general, and has 100% efficacy in meningitis and other extra-pulmonary TB locations. BCG effect is independent of TB control measures (case detection and treatment). Furthermore, BCG provides nonspecific protection from various infections and is used in the treatment of bladder cancer. By 2020, at least five technologies had already been established for the future development of anti-TB vaccines: cellular vaccines, protein subunits, nucleic acids, with adenovirus vector, and with recombinant influenza virus as a vector. There are currently more than 20 TB vaccine candidates under evaluation. History teaches, and the COVID-19 pandemic has confirmed, that vaccination is a fundamental instrument for the control of infectious diseases. Until a more effective vaccine becomes available, BCG will continue to be included in the Argentine National Vaccination Calendar for application to newborns.
Topics: BCG Vaccine; COVID-19; Humans; Infant, Newborn; Pandemics; SARS-CoV-2; Tuberculosis Vaccines; Vaccination
PubMed: 34875601
DOI: No ID Found -
Pharmacological Research Jan 2022Renal carcinoma progresses aggressively in patients with metastatic disease while curative strategies are limited. Here, we constructed a recombinant non-replicating...
Renal carcinoma progresses aggressively in patients with metastatic disease while curative strategies are limited. Here, we constructed a recombinant non-replicating adenovirus (Ad) vaccine encoding an immune activator, CD137L, and a tumor antigen, CAIX, for treating renal carcinoma. In a subcutaneous tumor model, tumor growth was significantly suppressed in the Ad-CD137L/CAIX vaccine group compared with the single vaccine group. The induction and maturity of CD11C and CD8CD11C dendritic cell (DC) subsets were promoted in Ad-CD137L/CAIX co-immunized mice. Furthermore, the Ad-CD137L/CAIX vaccine elicited stronger tumor-specific multifunctional CD8 T cell immune responses as demonstrated by increased proliferation and cytolytic function of CD8 T cells. Notably, depletion of CD8 T cells greatly compromised the effective protection provided by Ad-CD137L/CAIX vaccine, suggesting an irreplaceable role of CD8 T cells for the immunopotency of the vaccine. In both lung metastatic and orthotopic models, Ad-CD137L/CAIX vaccine treatment significantly decreased tumor metastasis and progression and increased the induction of tumor-specific multifunctional CD8 T cells, in contrast to treatment with the Ad-CAIX vaccine alone. The Ad-CD137L/CAIX vaccine also augmented the tumor-specific multifunctional CD8 T cell immune response in both orthotopic and metastatic models. These results indicated that Ad-CD137L/CAIX vaccine elicited a potent anti-tumor activity by inducing CD8DC-mediated multifunctional CD8 T cell immune responses. The potential strategy of CD137L-based vaccine might be served as a novel treatment for renal carcinoma or other malignant tumors.
Topics: 4-1BB Ligand; Adenovirus Vaccines; Animals; CD8-Positive T-Lymphocytes; Carbonic Anhydrase IX; Carcinoma, Renal Cell; Dendritic Cells; Female; HEK293 Cells; Humans; Interleukin-6; Kidney Neoplasms; Lung Neoplasms; Mice, Inbred BALB C; Mice
PubMed: 34915126
DOI: 10.1016/j.phrs.2021.106034 -
Cardiology in ReviewCOVID-19 is a prothrombotic and cardiac-damaging disease. There are 4 vaccines against COVID-19 currently approved in North America, including the mRNA vaccines by...
COVID-19 is a prothrombotic and cardiac-damaging disease. There are 4 vaccines against COVID-19 currently approved in North America, including the mRNA vaccines by Pfizer and Moderna, and the adenovirus vector vaccines by Johnson and Johnson and AstraZeneca. These vaccines have been proven effective in reducing morbidity and preventing mortality in patients who were exposed to COVID-19 infection, but the vaccines have also been associated with complications. Vaccine-induced thrombotic thrombocytopenia (VITT) has a similar pathogenesis to heparin-induced thrombocytopenia, with an inappropriate immune response leading to platelet activation, consumption of platelets, and thrombosis. It appears to be more common with the adenovirus vector vaccines. Secondary immune thrombocytopenic purpura has been reported with all COVID-19 vaccines and is distinct from VITT because there is no sign of platelet activation or thrombotic events. Myocarditis and pericarditis are often reported in young males following mRNA vaccines and is often associated with a full recovery. The long-term effects of VITT, secondary immune thrombocytopenic purpura, myocarditis, and pericarditis secondary to COVID-19 vaccines have yet to be elucidated. Continued surveillance for these complications after vaccination is crucial for accurate diagnosis and effective management. Patients should consult their physicians regarding repeated vaccine doses after experiencing an adverse effect.
PubMed: 35576367
DOI: 10.1097/CRD.0000000000000457 -
Glycoconjugate Journal Aug 2021Glycoconjugate vaccines, obtained by carbohydrates covalently bound to protein carriers, have contributed to fight diseases such as meningitidis, pneumonia and typhoid...
Glycoconjugate vaccines, obtained by carbohydrates covalently bound to protein carriers, have contributed to fight diseases such as meningitidis, pneumonia and typhoid fever. Despite new technologies such as RNA and adenovirus based vaccine have now reached the market, these approaches are unable to target carbohydrates which are key virulence factors.This issue intends to provide an overview on relevant directions where the field is evolving and serve as starting point to increase interest in this exciting and fundamental part of vaccinology.
Topics: Bacterial Vaccines; Glycoconjugates; Humans; Vaccines, Conjugate; Viral Vaccines
PubMed: 34169357
DOI: 10.1007/s10719-021-09997-5 -
The American Journal of Case Reports Feb 2022BACKGROUND Since December 2020, multiple vaccines have mobilized mass immunization campaigns capable of mitigating the current SARS-COV-2 pandemic. Ad26.COV2.S (Johnson...
BACKGROUND Since December 2020, multiple vaccines have mobilized mass immunization campaigns capable of mitigating the current SARS-COV-2 pandemic. Ad26.COV2.S (Johnson & Johnson/Janssen) is a recombinant, replication-incompetent vector vaccine encoding the SARS-CoV-2 spike (s) protein and is especially protective against severe-critical disease. It is a single-dose injection; adverse effects after vaccine administration are usually mild and self-limited, including pain at the injection site, headache, fatigue, muscle aches, and nausea. Severe adverse events involving hospitalization and death after Ad26.COV2.S rarely occur. However, not unlike previous viral vector vaccines, ongoing clinical trials may unveil rare complications of Ad26.COV2.S. Guillain-Barre Syndrome (GBS) is an autoimmune demyelinating polyneuropathy that can potentially manifest severe neurological symptoms after vaccination. CASE REPORT This report describes a case of classic GBS features that manifested 14 days after a single Ad26.COV2.S vaccine injection. The patient developed flaccid paralysis with treatment-related fluctuations. Our findings warrant further investigation into the potential relationship between SARS-CoV-2 vaccinations and the development of GBS. CONCLUSIONS A temporal association between the Ad26.COV2.S (Johnson & Johnson/Janssen) vaccine and the onset of GBS was demonstrated in this case report. A feasible underlying pathogenic mechanism involves the cross-reactivity of antibodies stimulated by adenovirus vaccine components and peripheral nerve glycoproteins. However, there is currently insufficient evidence to support a causal relationship between Ad26.COV2.S and the development of GBS. Further evidence gathered from clinician surveillance and clinical trials are needed to draw these conclusions.
Topics: Ad26COVS1; COVID-19; COVID-19 Vaccines; Guillain-Barre Syndrome; Humans; SARS-CoV-2; Vaccination
PubMed: 35157644
DOI: 10.12659/AJCR.935275 -
Vaccine Jun 2023During the COVID-19 pandemic multiple vaccines were rapidly developed and widely used throughout the world. At present there is very little information on COVID-19...
BACKGROUND
During the COVID-19 pandemic multiple vaccines were rapidly developed and widely used throughout the world. At present there is very little information on COVID-19 vaccine interactions with primary human immune cells such as peripheral blood mononuclear cells (PBMCs), monocyte-derived macrophages and dendritic cells (moDCs).
METHODS
Human PBMCs, macrophages and moDCs were stimulated with different COVID-19 vaccines, and the expression of interferon (IFN-λ1, IFN-α1), pro-inflammatory (IL-1β, IL-6, IL-8, IL-18, CXCL-4, CXCL-10, TNF-α) and Th1-type cytokine mRNAs (IL-2, IFN-γ) were analyzed by qPCR. In addition, the expression of vaccine induced spike (S) protein and antiviral molecules were studied in primary immune cells and in A549 lung epithelial cells.
RESULTS
Adenovirus vector (Ad-vector) vaccine AZD1222 induced high levels of IFN-λ1, IFN-α1, CXCL-10, IL-6, and TNF-α mRNAs in PBMCs at early time points of stimulation while the expression of IFN-γ and IL-2 mRNA took place at later times. AZD1222 also induced IFN-λ1, CXCL-10 and IL-6 mRNA expression in monocyte-derived macrophages and DCs in a dose-dependent fashion. AZD1222 also activated the phosphorylation of IRF3 and induced MxA expression. BNT162b2 and mRNA-1273 mRNA vaccines failed to induce or induced very weak cytokine gene expression in all cell models. None of the vaccines enhanced the expression of CXCL-4. AZD1222 and mRNA-1273 vaccines induced high expression of S protein in all studied cells.
CONCLUSIONS
Ad-vector vaccine induces higher IFN and pro-inflammatory responses than the mRNA vaccines in human immune cells. This data shows that AZD1222 readily activates IFN and pro-inflammatory cytokine gene expression in PBMCs, macrophages and DCs, but fails to further enhance CXCL-4 mRNA expression.
Topics: Humans; Interferons; Leukocytes, Mononuclear; COVID-19 Vaccines; ChAdOx1 nCoV-19; Tumor Necrosis Factor-alpha; mRNA Vaccines; BNT162 Vaccine; 2019-nCoV Vaccine mRNA-1273; Interleukin-2; Interleukin-6; Pandemics; Dendritic Cells; COVID-19; Cytokines; Macrophages; Vaccines; RNA, Messenger; Adenoviridae
PubMed: 37142461
DOI: 10.1016/j.vaccine.2023.04.049