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1.
Int J Mol Sci ; 22(3)2021 Jan 24.
Article in English | MEDLINE | ID: covidwho-1389388

ABSTRACT

The prevention and control of infectious diseases is crucial to the maintenance and protection of social and public healthcare. The global impact of SARS-CoV-2 has demonstrated how outbreaks of emerging and re-emerging infections can lead to pandemics of significant public health and socio-economic burden. Vaccination is one of the most effective approaches to protect against infectious diseases, and to date, multiple vaccines have been successfully used to protect against and eradicate both viral and bacterial pathogens. The main criterion of vaccine efficacy is the induction of specific humoral and cellular immune responses, and it is well established that immunogenicity depends on the type of vaccine as well as the route of delivery. In addition, antigen delivery to immune organs and the site of injection can potentiate efficacy of the vaccine. In light of this, microvesicles have been suggested as potential vehicles for antigen delivery as they can carry various immunogenic molecules including proteins, nucleic acids and polysaccharides directly to target cells. In this review, we focus on the mechanisms of microvesicle biogenesis and the role of microvesicles in infectious diseases. Further, we discuss the application of microvesicles as a novel and effective vaccine delivery system.


Subject(s)
COVID-19/prevention & control , Extracellular Vesicles/immunology , Immunologic Factors/immunology , SARS-CoV-2/immunology , Viral Vaccines/administration & dosage , Animals , COVID-19/immunology , Drug Delivery Systems/methods , Humans , Vaccination/methods , Viral Vaccines/immunology
2.
Clin Infect Dis ; 72(12): e978-e992, 2021 06 15.
Article in English | MEDLINE | ID: covidwho-1269557

ABSTRACT

BACKGROUND: Clinical outcomes of the interaction between the co-circulating pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and seasonal influenza viruses are unknown. METHODS: We established a golden Syrian hamster model coinfected by SARS-CoV-2 and mouse-adapted A(H1N1)pdm09 simultaneously or sequentially. The weight loss, clinical scores, histopathological changes, viral load and titer, and serum neutralizing antibody titer were compared with hamsters challenged by either virus. RESULTS: Coinfected hamsters had more weight loss, more severe lung inflammatory damage, and tissue cytokine/chemokine expression. Lung viral load, infectious virus titers, and virus antigen expression suggested that hamsters were generally more susceptible to SARS-CoV-2 than to A(H1N1)pdm09. Sequential coinfection with A(H1N1)pdm09 one day prior to SARS-CoV-2 exposure resulted in a lower lung SARS-CoV-2 titer and viral load than with SARS-CoV-2 monoinfection, but a higher lung A(H1N1)pdm09 viral load. Coinfection also increased intestinal inflammation with more SARS-CoV-2 nucleoprotein expression in enterocytes. Simultaneous coinfection was associated with delay in resolution of lung damage, lower serum SARS-CoV-2 neutralizing antibody, and longer SARS-CoV-2 shedding in oral swabs compared to that of SARS-CoV-2 monoinfection. CONCLUSIONS: Simultaneous or sequential coinfection by SARS-CoV-2 and A(H1N1)pdm09 caused more severe disease than monoinfection by either virus in hamsters. Prior A(H1N1)pdm09 infection lowered SARS-CoV-2 pulmonary viral loads but enhanced lung damage. Whole-population influenza vaccination for prevention of coinfection, and multiplex molecular diagnostics for both viruses to achieve early initiation of antiviral treatment for improvement of clinical outcome should be considered.


Subject(s)
COVID-19 , Coinfection , Influenza A Virus, H1N1 Subtype , Influenza, Human , Animals , Cricetinae , Disease Models, Animal , Humans , Mesocricetus , Mice , SARS-CoV-2
3.
J Immunother Cancer ; 9(6)2021 06.
Article in English | MEDLINE | ID: covidwho-1266401

ABSTRACT

SARS-CoV-2 infection and the resulting COVID-19 have afflicted millions of people in an ongoing worldwide pandemic. Safe and effective vaccination is needed urgently to protect not only the general population but also vulnerable subjects such as patients with cancer. Currently approved mRNA-based SARS-CoV-2 vaccines seem suitable for patients with cancer based on their mode of action, efficacy, and favorable safety profile reported in the general population. Here, we provide an overview of mRNA-based vaccines including their safety and efficacy. Extrapolating from insights gained from a different preventable viral infection, we review existing data on immunity against influenza A and B vaccines in patients with cancer. Finally, we discuss COVID-19 vaccination in light of the challenges specific to patients with cancer, such as factors that may hinder protective SARS-CoV-2 immune responses in the context of compromised immunity and the use of immune-suppressive or immune-modulating drugs.


Subject(s)
COVID-19 Vaccines , Neoplasms/therapy , RNA, Messenger , SARS-CoV-2/immunology , Viral Vaccines , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/genetics , COVID-19 Vaccines/therapeutic use , Drug Stability , Humans , Influenza, Human/epidemiology , Influenza, Human/immunology , Influenza, Human/prevention & control , Neoplasms/epidemiology , Neoplasms/immunology , Pandemics , RNA Stability/physiology , RNA, Messenger/administration & dosage , RNA, Messenger/adverse effects , RNA, Messenger/chemistry , RNA, Messenger/genetics , SARS-CoV-2/genetics , Vaccination/methods , Viral Vaccines/adverse effects , Viral Vaccines/chemistry , Viral Vaccines/genetics
4.
Nat Med ; 27(8): 1370-1378, 2021 08.
Article in English | MEDLINE | ID: covidwho-1263502

ABSTRACT

The effectiveness of COVID-19 vaccination in preventing new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the general community is still unclear. Here, we used the Office for National Statistics COVID-19 Infection Survey-a large community-based survey of individuals living in randomly selected private households across the United Kingdom-to assess the effectiveness of the BNT162b2 (Pfizer-BioNTech) and ChAdOx1 nCoV-19 (Oxford-AstraZeneca; ChAdOx1) vaccines against any new SARS-CoV-2 PCR-positive tests, split according to self-reported symptoms, cycle threshold value (<30 versus ≥30; as a surrogate for viral load) and gene positivity pattern (compatible with B.1.1.7 or not). Using 1,945,071 real-time PCR results from nose and throat swabs taken from 383,812 participants between 1 December 2020 and 8 May 2021, we found that vaccination with the ChAdOx1 or BNT162b2 vaccines already reduced SARS-CoV-2 infections ≥21 d after the first dose (61% (95% confidence interval (CI) = 54-68%) versus 66% (95% CI = 60-71%), respectively), with greater reductions observed after a second dose (79% (95% CI = 65-88%) versus 80% (95% CI = 73-85%), respectively). The largest reductions were observed for symptomatic infections and/or infections with a higher viral burden. Overall, COVID-19 vaccination reduced the number of new SARS-CoV-2 infections, with the largest benefit received after two vaccinations and against symptomatic and high viral burden infections, and with no evidence of a difference between the BNT162b2 and ChAdOx1 vaccines.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/epidemiology , COVID-19/virology , Humans , SARS-CoV-2/isolation & purification , United Kingdom/epidemiology
5.
Vaccines (Basel) ; 9(5)2021 May 18.
Article in English | MEDLINE | ID: covidwho-1234844

ABSTRACT

Due to their increased transmissibility, three variants of high concern have emerged in the United Kingdom (also known as B.1.1.7 lineage or VOC-202012/01), South Africa (B.1.351 lineage), and Brazil (P1 lineage) with multiple substitutions in the spike protein. Since neutralizing antibodies elicited by vaccination are likely considered as correlates of protection for SARS-CoV-2 infection, it is important to analyze whether vaccinees with mRNA BNT162b2 are equally protected against these emerging SARS-CoV-2 variants. To this aim, we enrolled healthy subjects one month after complete vaccination with Comirnaty and evaluated the neutralizing response against the native Wuhan strain and the emerging B.1.1.7, B.1.351 and P1 lineages, by using the microneutralization assay, currently considered the gold standard test for the evaluation and detection of functional neutralizing antibodies. The most remarkable finding of this study was the significantly lower neutralizing antibody titer against B.1.351 lineage, compared to the wild-type virus. No significant differences were observed with the other two lineages. These findings provide evidence that vaccinated subjects may not be equally protected against all SARS-CoV-2 lineages.

6.
Epidemiology ; 32(4): 508-517, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1232231

ABSTRACT

Observational studies of the effectiveness of vaccines to prevent COVID-19 are needed to inform real-world use. Such studies are now underway amid the ongoing rollout of SARS-CoV-2 vaccines globally. Although traditional case-control and test-negative design studies feature prominently among strategies used to assess vaccine effectiveness, such studies may encounter important threats to validity. Here, we review the theoretical basis for estimation of vaccine direct effects under traditional case-control and test-negative design frameworks, addressing specific natural history parameters of SARS-CoV-2 infection and COVID-19 relevant to these designs. Bias may be introduced by misclassification of cases and controls, particularly when clinical case criteria include common, nonspecific indicators of COVID-19. When using diagnostic assays with high analytical sensitivity for SARS-CoV-2 detection, individuals testing positive may be counted as cases even if their symptoms are due to other causes. The traditional case-control design may be particularly prone to confounding due to associations of vaccination with healthcare-seeking behavior or risk of infection. The test-negative design reduces but may not eliminate this confounding, for instance, if individuals who receive vaccination seek care or testing for less-severe illness. These circumstances indicate the two study designs cannot be applied naively to datasets gathered through public health surveillance or administrative sources. We suggest practical strategies to reduce bias in vaccine effectiveness estimates at the study design and analysis stages.


Subject(s)
COVID-19 , Vaccines , COVID-19 Vaccines , Humans , Retrospective Studies , SARS-CoV-2
7.
Nature ; 594(7864): 553-559, 2021 06.
Article in English | MEDLINE | ID: covidwho-1221200

ABSTRACT

Betacoronaviruses caused the outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, as well as the current pandemic of SARS coronavirus 2 (SARS-CoV-2)1-4. Vaccines that elicit protective immunity against SARS-CoV-2 and betacoronaviruses that circulate in animals have the potential to prevent future pandemics. Here we show that the immunization of macaques with nanoparticles conjugated with the receptor-binding domain of SARS-CoV-2, and adjuvanted with 3M-052 and alum, elicits cross-neutralizing antibody responses against bat coronaviruses, SARS-CoV and SARS-CoV-2 (including the B.1.1.7, P.1 and B.1.351 variants). Vaccination of macaques with these nanoparticles resulted in a 50% inhibitory reciprocal serum dilution (ID50) neutralization titre of 47,216 (geometric mean) for SARS-CoV-2, as well as in protection against SARS-CoV-2 in the upper and lower respiratory tracts. Nucleoside-modified mRNAs that encode a stabilized transmembrane spike or monomeric receptor-binding domain also induced cross-neutralizing antibody responses against SARS-CoV and bat coronaviruses, albeit at lower titres than achieved with the nanoparticles. These results demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses, and provide a multimeric protein platform for the further development of vaccines against multiple (or all) betacoronaviruses.


Subject(s)
Antibodies, Neutralizing/immunology , Betacoronavirus/immunology , COVID-19/immunology , COVID-19/prevention & control , Common Cold/prevention & control , Cross Reactions/immunology , Pandemics , Viral Vaccines/immunology , Adjuvants, Immunologic , Administration, Intranasal , Animals , COVID-19/epidemiology , COVID-19 Vaccines/immunology , Common Cold/immunology , Common Cold/virology , Disease Models, Animal , Female , Humans , Macaca/immunology , Male , Models, Molecular , Nanoparticles/chemistry , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Trachea , Vaccination
8.
Curr Nutr Rep ; 10(3): 200-210, 2021 09.
Article in English | MEDLINE | ID: covidwho-1216278

ABSTRACT

PURPOSE OF REVIEW: The SARS-CoV-2 (COVID-19) outbreak has manifested into a major public health concern across the globe, affecting particularly the most vulnerable population groups. Currently, there are various clinical trials being conducted to develop effective treatments. It is estimated that it could take one or more years before these drugs pass all safety tests and concrete results with regard to their effectiveness become available. In addition, despite the recent development of vaccines (licensed for use under conditional licenses) and the commencement of COVID-19 vaccination programs in several countries, there is still a need for safe and novel strategies that may reduce the symptomatology and/or prevent the severe complications associated with COVID-19. Natural compounds previously shown to have antiviral potential should be thoroughly considered and investigated for use in prophylactic treatment of COVID-19 due to their availability and safety. RECENT FINDINGS: The current narrative review investigates whether there is evidence in the literature that supplementation with dietary minerals and vitamins may have a role in preventing infection with SARS-CoV-2 or in reducing COVID-19 symptomatology and disease progression. The current evidence from the literature supports that zinc and vitamin C have a potential in reducing the inflammatory response associated with SARS-CoV-2 while folate and vitamin D may have a role in antagonizing the entry of SARs-CoV-2 virus in host calls. Thus, further research should be conducted that could lead to the development of nutritional supplements involving natural and widely available compounds such as zinc, folate, vitamin C, and vitamin D. The latter could be an effective, safe, and inexpensive way to either prevent infection with SARS-CoV-2 and/or lessen the burden of COVID-19 disease.


Subject(s)
COVID-19/prevention & control , Micronutrients/administration & dosage , Vitamins/administration & dosage , Ascorbic Acid , Dietary Supplements , Folic Acid , Humans , Pandemics , Vitamin D , Zinc
9.
Hum Vaccin Immunother ; 17(9): 3126-3130, 2021 Sep 02.
Article in English | MEDLINE | ID: covidwho-1207210

ABSTRACT

Aims: An observational study of a retrospective cohort was performed to assess the impact of influenza vaccination (IV) on the risk of SARS-CoV-2 infection in a population of middle-aged people for 8 weeks after IV and compared with an unvaccinated group.Patients and methods: Data from 1098 middle-aged patients (53.7 ± 4.7 years) after IV and 1205 unvaccinated patients (50.1 ± 6.8 years) were analyzed based on medical documentation. The inclusion criteria were age between 40 - 60 years and IV in the period from 1-30 September 2020. The incidence of infection with SARS-CoV-2 was confirmed by PCR and the classification of ICD-10 (U07.1).Results and conclusions: After IV, patients had significantly fewer SARS-CoV-2 infections than the unvaccinated patients (P = .017). The hazard ratio was 0.74 (95% CI: 0.54-0.89). IV may partially reduce the risk of SARS-CoV-2 infection.


Subject(s)
COVID-19 , Influenza, Human , Adult , Humans , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Middle Aged , Retrospective Studies , SARS-CoV-2 , Vaccination
10.
J Thromb Haemost ; 19(7): 1813-1818, 2021 07.
Article in English | MEDLINE | ID: covidwho-1205972

ABSTRACT

BACKGROUND: The COVID-19 vaccine from AstraZeneca (AZD1222) is one of several vaccines introduced to provide immunity against SARS-CoV-2. Recently, more than 50 cases have been reported presenting a combination of thrombosis, thrombocytopenia, and remarkably high levels of anti-platelet factor 4 (PF4)/polyanion antibodies post-AZD1222 vaccination. Now linked to the vaccine, the condition is referred to as vaccine-induced immune thrombotic thrombocytopenia. The European Medicines Agency still recommends vaccination with AZD1222, but several European countries have temporally paused and/or restricted its use because of the perceived risk of this severe side effect. Because there is no description of PF4/polyanion antibody testing in the clinical trials, knowledge about the prevalence of such antibodies in a vaccinated cohort is needed. OBJECTIVES: To investigate prevalence of thrombocytopenia and anti-PF4/polyanion antibodies in a population recently vaccinated with AZD1222. PATIENTS/METHODS: Four hundred and ninety-two health care workers recently vaccinated with the first dose of AZD1222 were recruited from two hospitals in Norway. Study individuals were screened for thrombocytopenia and the presence of anti-PF4/polyanion antibodies with a PF4/PVS immunoassay. Side effects after vaccination were registered. RESULTS: The majority of study participants had normal platelet counts and negative immunoassay. Anti-PF4/polyanion antibodies without platelet activating properties were only detected in six individuals (optical density ≥0.4, range 0.58-1.16), all with normal platelet counts. No subjects had severe thrombocytopenia. CONCLUSIONS: We found low prevalence of both thrombocytopenia and antibodies to PF4/polyanion-complexes among Norwegian health care workers after vaccination with AZD1222.


Subject(s)
COVID-19 , Thrombocytopenia , COVID-19 Vaccines , Europe , Health Personnel , Heparin , Humans , Norway/epidemiology , Platelet Factor 4 , Polyelectrolytes , Prevalence , SARS-CoV-2 , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Thrombocytopenia/epidemiology , Vaccination
11.
JAMA Netw Open ; 4(4): e214347, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1168797

ABSTRACT

Importance: A strategy that prioritizes individuals for SARS-CoV-2 vaccination according to their risk of SARS-CoV-2-related mortality would help minimize deaths during vaccine rollout. Objective: To develop a model that estimates the risk of SARS-CoV-2-related mortality among all enrollees of the US Department of Veterans Affairs (VA) health care system. Design, Setting, and Participants: This prognostic study used data from 7 635 064 individuals enrolled in the VA health care system as of May 21, 2020, to develop and internally validate a logistic regression model (COVIDVax) that predicted SARS-CoV-2-related death (n = 2422) during the observation period (May 21 to November 2, 2020) using baseline characteristics known to be associated with SARS-CoV-2-related mortality, extracted from the VA electronic health records (EHRs). The cohort was split into a training period (May 21 to September 30) and testing period (October 1 to November 2). Main Outcomes and Measures: SARS-CoV-2-related death, defined as death within 30 days of testing positive for SARS-CoV-2. VA EHR data streams were imported on a data integration platform to demonstrate that the model could be executed in real-time to produce dashboards with risk scores for all current VA enrollees. Results: Of 7 635 064 individuals, the mean (SD) age was 66.2 (13.8) years, and most were men (7 051 912 [92.4%]) and White individuals (4 887 338 [64.0%]), with 1 116 435 (14.6%) Black individuals and 399 634 (5.2%) Hispanic individuals. From a starting pool of 16 potential predictors, 10 were included in the final COVIDVax model, as follows: sex, age, race, ethnicity, body mass index, Charlson Comorbidity Index, diabetes, chronic kidney disease, congestive heart failure, and Care Assessment Need score. The model exhibited excellent discrimination with area under the receiver operating characteristic curve (AUROC) of 85.3% (95% CI, 84.6%-86.1%), superior to the AUROC of using age alone to stratify risk (72.6%; 95% CI, 71.6%-73.6%). Assuming vaccination is 90% effective at preventing SARS-CoV-2-related death, using this model to prioritize vaccination was estimated to prevent 63.5% of deaths that would occur by the time 50% of VA enrollees are vaccinated, significantly higher than the estimate for prioritizing vaccination based on age (45.6%) or the US Centers for Disease Control and Prevention phases of vaccine allocation (41.1%). Conclusions and Relevance: In this prognostic study of all VA enrollees, prioritizing vaccination based on the COVIDVax model was estimated to prevent a large proportion of deaths expected to occur during vaccine rollout before sufficient herd immunity is achieved.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Health Planning/methods , Health Priorities/statistics & numerical data , Mass Vaccination , Veterans/statistics & numerical data , Aged , Area Under Curve , Comorbidity , Female , Humans , Logistic Models , Male , Middle Aged , Prognosis , ROC Curve , Risk Assessment , Risk Factors , SARS-CoV-2 , United States
12.
Clin Transl Immunology ; 10(4): e1269, 2021.
Article in English | MEDLINE | ID: covidwho-1162553

ABSTRACT

OBJECTIVES: Efforts to develop and deploy effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue at pace. Here, we describe rational antigen design through to manufacturability and vaccine efficacy of a prefusion-stabilised spike (S) protein, Sclamp, in combination with the licensed adjuvant MF59 'MF59C.1' (Seqirus, Parkville, Australia). METHODS: A panel recombinant Sclamp proteins were produced in Chinese hamster ovary and screened in vitro to select a lead vaccine candidate. The structure of this antigen was determined by cryo-electron microscopy and assessed in mouse immunogenicity studies, hamster challenge studies and safety and toxicology studies in rat. RESULTS: In mice, the Sclamp vaccine elicits high levels of neutralising antibodies, as well as broadly reactive and polyfunctional S-specific CD4+ and cytotoxic CD8+ T cells in vivo. In the Syrian hamster challenge model (n = 70), vaccination results in reduced viral load within the lung, protection from pulmonary disease and decreased viral shedding in daily throat swabs which correlated strongly with the neutralising antibody level. CONCLUSION: The SARS-CoV-2 Sclamp vaccine candidate is compatible with large-scale commercial manufacture, stable at 2-8°C. When formulated with MF59 adjuvant, it elicits neutralising antibodies and T-cell responses and provides protection in animal challenge models.

13.
Pathol Res Pract ; 221: 153417, 2021 May.
Article in English | MEDLINE | ID: covidwho-1157673

ABSTRACT

The COVID-19 (coronavirus disease) pandemic caused by SARS-CoV-2 with its rapid expansion has led to extraordinary implications in our understanding of viral infections and their management globally. In this current scenario of unusual circumstances and public health emergency, the cancer care per se is facing unprecedented challenges. The peculiarity of the SARS-CoV-2 infections is still being uncovered as the pandemic spreads across the populations than showing signs of its curtailment. The review highlights the significance of idiosyncrasy of the SARS-Cov-2 infection especially putting forth the importance of immunosenescence, both in the COVID-19 specific immune response in the infected lungs of the elderly and in the cancer patients infected with SARS-CoV-2.The focus of the article is directed towards demystifying the unparalleled essence of a proprotein convertase, Furin in the biology of the SARS-Cov-2 infection and its role in facilitating viral transmission through expedited cellular entry into alveolar epithelial cells in COVID-19 infected cancer patients. The risk stratification of the cancer treatment and guidelines shaped up by national and international oncology societies in providing uncompromised patient care during the COVID-19 crisis have also been addressed. The global efforts towards vaccination in developing SARS CoV-2 immunity are also discussed in this article.


Subject(s)
COVID-19 , Furin/metabolism , Neoplasms , SARS-CoV-2/physiology , COVID-19/immunology , COVID-19/metabolism , Comorbidity , Humans , Immunosenescence , Neoplasms/epidemiology , Neoplasms/immunology , Virus Internalization
14.
Vaccines (Basel) ; 9(4)2021 Mar 24.
Article in English | MEDLINE | ID: covidwho-1154565

ABSTRACT

The unprecedented and rapid spread of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) has motivated the need for a rapidly producible and scalable vaccine. Here, we developed a synthetic soluble SARS-CoV-2 spike (S) DNA-based vaccine candidate, GX-19. In mice, immunization with GX-19 elicited not only S-specific systemic and pulmonary antibody responses but also Th1-biased T cell responses in a dose-dependent manner. GX-19-vaccinated nonhuman primates seroconverted rapidly and exhibited a detectable neutralizing antibody response as well as multifunctional CD4+ and CD8+ T cell responses. Notably, when the immunized nonhuman primates were challenged at 10 weeks after the last vaccination with GX-19, they had reduced viral loads in contrast to non-vaccinated primates as a control. These findings indicate that GX-19 vaccination provides a durable protective immune response and also support further development of GX-19 as a vaccine candidate for SARS-CoV-2.

16.
Cell Host Microbe ; 29(2): 236-249.e6, 2021 02 10.
Article in English | MEDLINE | ID: covidwho-978240

ABSTRACT

To develop a vaccine candidate against coronavirus disease 2019 (COVID-19), we generated a lentiviral vector (LV) eliciting neutralizing antibodies against the Spike glycoprotein of SARS-CoV-2. Systemic vaccination by this vector in mice, in which the expression of the SARS-CoV-2 receptor hACE2 has been induced by transduction of respiratory tract cells by an adenoviral vector, confers only partial protection despite high levels of serum neutralizing activity. However, eliciting an immune response in the respiratory tract through an intranasal boost results in a >3 log10 decrease in the lung viral loads and reduces local inflammation. Moreover, both integrative and non-integrative LV platforms display strong vaccine efficacy and inhibit lung deleterious injury in golden hamsters, which are naturally permissive to SARS-CoV-2 replication and closely mirror human COVID-19 physiopathology. Our results provide evidence of marked prophylactic effects of LV-based vaccination against SARS-CoV-2 and designate intranasal immunization as a powerful approach against COVID-19.


Subject(s)
Administration, Intranasal/methods , COVID-19 Vaccines/administration & dosage , COVID-19/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , Cricetinae , Female , Genetic Vectors , Immunity, Mucosal , Immunization, Secondary , Immunoglobulin A/immunology , Lentivirus/genetics , Lentivirus/immunology , Male , Mice , Models, Animal , Respiratory System/immunology , Spike Glycoprotein, Coronavirus/immunology , Viral Load
17.
Curr Pharm Des ; 27(13): 1553-1563, 2021.
Article in English | MEDLINE | ID: covidwho-890256

ABSTRACT

For nearly two decades, coronaviruses have caused many health and economic problems, while no effective commercial vaccine has yet been developed. It is worth mentioning that despite some mutations and recombination in SARS-CoV-2, its genotype is very close to the original strain from Wuhan, China. Therefore, the development of an effective vaccine would be promising. It might be hypothesized that BCG vaccination is performed in high-risk populations before the commercialization of an effective SARS-CoV-2 vaccine. However, the development of an effective vaccine without considering the adverse immune reactions derived from antibody-dependent or cell-based immune enhancement may threaten vaccinated people's lives and long-term side effects must be considered. To this end, targeting of the receptor-binding domain (RBD) in spike and not whole spike, glycolization of FC receptors, PD-1 blockers, CPPs, etc., are promising. Therefore, the subunit vaccines or RNA vaccines that encode the RBP segment of the spike are of interest. To enhance the vaccine efficacy, its co-delivery with an adjuvant has been recommended. Nanoparticles modulate immune response with higher efficiency than the soluble form of antigens and can be functionalized with the positively charged moieties and ligands of targeted cells, such as dendritic cells, to increase cellular uptake of the antigens and their presentation on the surface of immune cells. This research aimed to discuss the COVID-19 vaccines entering the clinical trial and their mode of action effective immunity against the virus and discusses their advantages compared to each other.


Subject(s)
COVID-19 , Viral Vaccines , COVID-19 Vaccines , China , Humans , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
18.
Expert Rev Vaccines ; 19(10): 919-936, 2020 10.
Article in English | MEDLINE | ID: covidwho-772835

ABSTRACT

Introduction Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), has quickly spread around the world. Areas covered This review will discuss the available immunologic and clinical evidence to support the benefit of the influenza, pneumococcal, and tuberculosis vaccines in the context of COVID-19 as well as to provide an overview on the COVID-19-specific vaccines that are in the development pipeline. In addition, implications for vaccination strategies from a public health perspective will be discussed. Expert opinion Some vaccines are being considered for their potentially beneficial role in preventing or improving the prognosis of COVID-19: influenza, pneumococcal and tuberculosis vaccines. These vaccines may have either direct effect on COVID-19 via different types of immune responses or indirect effects by reducing the burden of viral and bacterial respiratory diseases on individual patients and national healthcare system and by facilitating differential diagnoses with other viral/bacterial respiratory disease. On the other hand, a large number of candidate vaccines against SARS-CoV-2 are currently in the pipeline and undergoing phase I, II, and III clinical studies. As SARS-CoV-2 vaccines are expected to be marketed through accelerated regulatory pathways, vaccinovigilance as well as planning of a successful vaccination campaign will play a major role in protecting public health.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Vaccination , COVID-19/immunology , COVID-19 Vaccines/immunology , Drug Development , Humans , Pharmacovigilance , Public Health , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification
19.
Cell Immunol ; 356: 104187, 2020 10.
Article in English | MEDLINE | ID: covidwho-679683

ABSTRACT

Mycobacterium bovis BCG, a live attenuated tuberculosis vaccine offers protection against disseminated TB in children. BCG exhibits heterologous protective effects against unrelated infections and reduces infant mortality due to non-mycobacterial infections. Recent reports have suggested that BCG vaccination might have protective effects against COVID-19, however it is highly unlikely that BCG vaccine in its current form can offer complete protection against SARS-CoV-2 infection due to the lack of specific immunity. Nonetheless, recombinant BCG strains expressing antigens of SARS-CoV-2 may offer protection against COVID-19 due to the activation of innate as well as specific adaptive immune response. Further proven safety records of BCG in humans, its adjuvant activity and low cost manufacturing makes it a frontrunner in the vaccine development to stop this pandemic. In this review we discuss about the heterologous effects of BCG, induction of trained immunity and its implication in development of a potential vaccine against COVID-19 pandemic.


Subject(s)
BCG Vaccine/therapeutic use , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Betacoronavirus , COVID-19 , Humans , Immunity, Innate , Immunologic Memory , SARS-CoV-2 , Vaccines, Attenuated/therapeutic use
20.
Front Immunol ; 11: 970, 2020.
Article in English | MEDLINE | ID: covidwho-400215

ABSTRACT

Trained immunity is a type of non-specific memory-like immune response induced by some pathogens and vaccines, such as BCG, which can confer antigen-independent protection against a wide variety of pathogens. The BCG vaccine has been extensively used to protect against tuberculosis for almost a 100 years. Interestingly, this vaccine reduces children's mortality caused by infections unrelated to Mycobacterium tuberculosis infection, a phenomenon thought to be due to the induction of trained immunity. The SARS-CoV-2 pandemic has infected, as of April 22, 2020, 2,623,231 people globally, causing a major public health problem worldwide. Currently, no vaccine or treatment is available to control this pandemic. We analyzed the number of positive cases and deaths in different countries and correlated them with the inclusion of BCG vaccination at birth in their national vaccination programs. Interestingly, those countries where BCG vaccination is given at birth have shown a lower contagion rate and fewer COVID-19-related deaths, suggesting that this vaccine may induce trained immunity that could confer some protection for SARS-CoV-2.


Subject(s)
BCG Vaccine/immunology , Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Immunogenicity, Vaccine , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/immunology , Adult , COVID-19 , COVID-19 Vaccines , Child , Coronavirus Infections/immunology , Humans , Immunity, Innate , Immunologic Memory , Pneumonia, Viral/immunology , SARS-CoV-2
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