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2.
Life Sci ; 280: 119744, 2021 Sep 01.
Article in English | MEDLINE | ID: covidwho-1281492

ABSTRACT

Viral respiratory tract infections have significantly impacted global health as well as socio-economic growth. Respiratory viruses such as the influenza virus, respiratory syncytial virus (RSV), and the recent SARS-CoV-2 infection (COVID-19) typically infect the upper respiratory tract by entry through the respiratory mucosa before reaching the lower respiratory tract, resulting in respiratory disease. Generally, vaccination is the primary method in preventing virus pathogenicity and it has been shown to remarkably reduce the burden of various infectious diseases. Nevertheless, the efficacy of conventional vaccines may be hindered by certain limitations, prompting the need to develop novel vaccine delivery vehicles to immunize against various strains of respiratory viruses and to mitigate the risk of a pandemic. In this review, we provide an insight into how polymer-based nanoparticles can be integrated with the development of vaccines to effectively enhance immune responses for combating viral respiratory tract infections.


Subject(s)
Nanoparticles/chemistry , Polymers/chemistry , Respiratory Tract Infections/prevention & control , Respiratory Tract Infections/virology , Vaccination , Viral Vaccines/administration & dosage , Animals , COVID-19/prevention & control , COVID-19/virology , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Drug Carriers/chemistry , Humans , Influenza, Human/prevention & control , Influenza, Human/virology , Orthomyxoviridae Infections/prevention & control , Orthomyxoviridae Infections/virology , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Virus Infections/virology , Vaccination/methods , Viral Vaccines/therapeutic use
3.
Microbiol Immunol ; 64(1): 33-51, 2020 Jan.
Article in English | MEDLINE | ID: covidwho-1262996

ABSTRACT

The spike (S) protein of coronavirus, which binds to cellular receptors and mediates membrane fusion for cell entry, is a candidate vaccine target for blocking coronavirus infection. However, some animal studies have suggested that inadequate immunization against severe acute respiratory syndrome coronavirus (SARS-CoV) induces a lung eosinophilic immunopathology upon infection. The present study evaluated two kinds of vaccine adjuvants for use with recombinant S protein: gold nanoparticles (AuNPs), which are expected to function as both an antigen carrier and an adjuvant in immunization; and Toll-like receptor (TLR) agonists, which have previously been shown to be an effective adjuvant in an ultraviolet-inactivated SARS-CoV vaccine. All the mice immunized with more than 0.5 µg S protein without adjuvant escaped from SARS after infection with mouse-adapted SARS-CoV; however, eosinophilic infiltrations were observed in the lungs of almost all the immunized mice. The AuNP-adjuvanted protein induced a strong IgG response but failed to improve vaccine efficacy or to reduce eosinophilic infiltration because of highly allergic inflammatory responses. Whereas similar virus titers were observed in the control animals and the animals immunized with S protein with or without AuNPs, Type 1 interferon and pro-inflammatory responses were moderate in the mice treated with S protein with and without AuNPs. On the other hand, the TLR agonist-adjuvanted vaccine induced highly protective antibodies without eosinophilic infiltrations, as well as Th1/17 cytokine responses. The findings of this study will support the development of vaccines against severe pneumonia-associated coronaviruses.


Subject(s)
Adjuvants, Immunologic/pharmacology , Coronavirus Infections/prevention & control , Gold/chemistry , Immunoglobulin G/immunology , Lung/immunology , Metal Nanoparticles/chemistry , Severe Acute Respiratory Syndrome/prevention & control , Spike Glycoprotein, Coronavirus/immunology , Analysis of Variance , Animals , Antibodies, Viral/immunology , Chlorocebus aethiops , Coronavirus/immunology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cytokines/metabolism , Disease Models, Animal , Female , Immunization , Lung/pathology , Mice , Mice, Inbred BALB C , Recombinant Proteins/immunology , SARS Virus/immunology , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/virology , Spike Glycoprotein, Coronavirus/genetics , Toll-Like Receptors , Vaccination , Vaccines, Synthetic , Vero Cells , Viral Envelope Proteins/genetics , Viral Envelope Proteins/immunology , Viral Vaccines/immunology , Viral Vaccines/pharmacology , Viral Vaccines/therapeutic use
4.
Front Immunol ; 11: 575074, 2020.
Article in English | MEDLINE | ID: covidwho-1256374

ABSTRACT

Combined cellular and humoral host immune response determine the clinical course of a viral infection and effectiveness of vaccination, but currently the cellular immune response cannot be measured on simple blood samples. As functional activity of immune cells is determined by coordinated activity of signaling pathways, we developed mRNA-based JAK-STAT signaling pathway activity assays to quantitatively measure the cellular immune response on Affymetrix expression microarray data of various types of blood samples from virally infected patients (influenza, RSV, dengue, yellow fever, rotavirus) or vaccinated individuals, and to determine vaccine immunogenicity. JAK-STAT1/2 pathway activity was increased in blood samples of patients with viral, but not bacterial, infection and was higher in influenza compared to RSV-infected patients, reflecting known differences in immunogenicity. High JAK-STAT3 pathway activity was associated with more severe RSV infection. In contrast to inactivated influenza virus vaccine, live yellow fever vaccine did induce JAK-STAT1/2 pathway activity in blood samples, indicating superior immunogenicity. Normal (healthy) JAK-STAT1/2 pathway activity was established, enabling assay interpretation without the need for a reference sample. The JAK-STAT pathway assays enable measurement of cellular immune response for prognosis, therapy stratification, vaccine development, and clinical testing.


Subject(s)
Dengue Virus/immunology , Immunity, Cellular , Orthomyxoviridae/immunology , Respiratory Syncytial Virus, Human/immunology , Rotavirus/immunology , Viral Vaccines/therapeutic use , Virus Diseases/immunology , Yellow fever virus/immunology , Biomarkers/blood , Dengue/blood , Dengue/immunology , Dengue/prevention & control , Dengue/virology , Dengue Vaccines/therapeutic use , Dengue Virus/pathogenicity , Diagnosis, Differential , Host-Pathogen Interactions , Humans , Immunogenicity, Vaccine , Influenza Vaccines/therapeutic use , Influenza, Human/blood , Influenza, Human/immunology , Influenza, Human/prevention & control , Influenza, Human/virology , Oligonucleotide Array Sequence Analysis , Orthomyxoviridae/pathogenicity , Predictive Value of Tests , RNA, Messenger/blood , RNA, Messenger/genetics , Respiratory Syncytial Virus Infections/blood , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Virus, Human/pathogenicity , Rotavirus/pathogenicity , Rotavirus Infections/blood , Rotavirus Infections/immunology , Rotavirus Infections/prevention & control , Rotavirus Infections/virology , Rotavirus Vaccines , Signal Transduction/genetics , Virus Diseases/blood , Virus Diseases/prevention & control , Virus Diseases/virology , Yellow Fever/blood , Yellow Fever/immunology , Yellow Fever/prevention & control , Yellow Fever/virology , Yellow Fever Vaccine/therapeutic use , Yellow fever virus/pathogenicity
5.
J Med Virol ; 93(4): 1943-1949, 2021 04.
Article in English | MEDLINE | ID: covidwho-1217363

ABSTRACT

Live unattenuated vaccines (LUVs) have been neglected for decades, due to widespread prejudice against their safety, even though they have successfully controlled yellow fever and adenovirus infection in humans as well as rinderpest and infectious bursal disease in animals. This review elucidated that LUVs could be highly safe with selective use of neutralizing antivirus antibodies, natural antiglycan antibodies, nonantibody antivirals, and ectopic inoculation. Also, LUVs could be of high efficacy, high development speed, and high production efficiency, with the development of humanized monoclonal antibodies and other modern technologies. They could circumvent antibody-dependent enhancement and maternal-derived antibody interference. With these important advantages, LUVs could be more powerful than other vaccines for controlling some viral diseases, and they warrant urgent investigation with animal experiments and clinical trials for defeating the COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2.


Subject(s)
Vaccines, Live, Unattenuated/therapeutic use , Viral Vaccines/therapeutic use , Virus Diseases/prevention & control , Animals , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/immunology , Antibodies, Viral/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Injections, Intramuscular , Vaccination/methods
6.
JCI Insight ; 6(10)2021 05 24.
Article in English | MEDLINE | ID: covidwho-1197299

ABSTRACT

Emerging coronaviruses from zoonotic reservoirs, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been associated with human-to-human transmission and significant morbidity and mortality. Here, we study both intradermal and intramuscular 2-dose delivery regimens of an advanced synthetic DNA vaccine candidate encoding a full-length MERS-CoV spike (S) protein, which induced potent binding and neutralizing antibodies as well as cellular immune responses in rhesus macaques. In a MERS-CoV challenge, all immunized rhesus macaques exhibited reduced clinical symptoms, lowered viral lung load, and decreased severity of pathological signs of disease compared with controls. Intradermal vaccination was dose sparing and more effective in this model at protecting animals from disease. The data support the further study of this vaccine for preventing MERS-CoV infection and transmission, including investigation of such vaccines and simplified delivery routes against emerging coronaviruses.


Subject(s)
Coronavirus Infections/veterinary , Macaca mulatta/immunology , Middle East Respiratory Syndrome Coronavirus/immunology , Vaccines, DNA/therapeutic use , Viral Vaccines/therapeutic use , Animals , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Immunogenicity, Vaccine , Injections, Intradermal , Middle East Respiratory Syndrome Coronavirus/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vaccines, DNA/administration & dosage , Vaccines, DNA/genetics , Viral Vaccines/administration & dosage , Viral Vaccines/genetics
7.
Int J Mol Sci ; 22(6)2021 Mar 20.
Article in English | MEDLINE | ID: covidwho-1143520

ABSTRACT

The recent pandemic Sars-CoV2 infection and studies on previous influenza epidemic have drawn attention to the association between the obesity and infectious diseases susceptibility and worse outcome. Metabolic complications, nutritional aspects, physical inactivity, and a chronic unbalance in the hormonal and adipocytokine microenvironment are major determinants in the severity of viral infections in obesity. By these pleiotropic mechanisms obesity impairs immune surveillance and the higher leptin concentrations produced by adipose tissue and that characterize obesity substantially contribute to such immune response dysregulation. Indeed, leptin not only controls energy balance and body weight, but also plays a regulatory role in the interplay between energy metabolism and immune system. Since leptin receptor is expressed throughout the immune system, leptin may exert effects on cells of both innate and adaptive immune system. Chronic inflammatory states due to metabolic (i.e., obesity) as well as infectious diseases increase leptin concentrations and consequently lead to leptin resistance further fueling inflammation. Multiple factors, including inflammation and ER stress, contribute to leptin resistance. Thus, if leptin is recognized as one of the adipokines responsible for the low grade inflammation found in obesity, on the other hand, impairments of leptin signaling due to leptin resistance appear to blunt the immunologic effects of leptin and possibly contribute to impaired vaccine-induced immune responses. However, many aspects concerning leptin interactions with inflammation and immune system as well as the therapeutical approaches to overcome leptin resistance and reduced vaccine effectiveness in obesity remain a challenge for future research.


Subject(s)
Leptin/immunology , Leptin/metabolism , Obesity/complications , Obesity/virology , Virus Diseases/complications , Animals , Antiviral Agents/therapeutic use , COVID-19/complications , COVID-19/drug therapy , COVID-19/immunology , COVID-19/metabolism , Energy Metabolism/immunology , Humans , Immune System/metabolism , Immune System/virology , Obesity/immunology , Obesity/metabolism , Viral Vaccines/therapeutic use , Virus Diseases/drug therapy , Virus Diseases/immunology , Virus Diseases/metabolism
9.
Nat Commun ; 12(1): 1403, 2021 03 03.
Article in English | MEDLINE | ID: covidwho-1117351

ABSTRACT

SARS-CoV-2 vaccines are advancing into human clinical trials, with emphasis on eliciting high titres of neutralising antibodies against the viral spike (S). However, the merits of broadly targeting S versus focusing antibody onto the smaller receptor binding domain (RBD) are unclear. Here we assess prototypic S and RBD subunit vaccines in homologous or heterologous prime-boost regimens in mice and non-human primates. We find S is highly immunogenic in mice, while the comparatively poor immunogenicity of RBD is associated with limiting germinal centre and T follicular helper cell activity. Boosting S-primed mice with either S or RBD significantly augments neutralising titres, with RBD-focussing driving moderate improvement in serum neutralisation. In contrast, both S and RBD vaccines are comparably immunogenic in macaques, eliciting serological neutralising activity that generally exceed levels in convalescent humans. These studies confirm recombinant S proteins as promising vaccine candidates and highlight multiple pathways to achieving potent serological neutralisation.


Subject(s)
COVID-19 Vaccines/therapeutic use , SARS-CoV-2/pathogenicity , Animals , Antibodies, Neutralizing/immunology , Antibody Formation/physiology , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Humans , Macaca , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Helper-Inducer/metabolism , Viral Vaccines/therapeutic use
10.
mBio ; 12(2)2021 03 02.
Article in English | MEDLINE | ID: covidwho-1115090

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of the CoV disease 2019 (COVID-19) pandemic, enters host cells via the interaction of its receptor-binding domain (RBD) of the spike protein with host angiotensin-converting enzyme 2 (ACE2). Therefore, the RBD is a promising vaccine target to induce protective immunity against SARS-CoV-2 infection. In this study, we report the development of an RBD protein-based vaccine candidate against SARS-CoV-2 using self-assembling Helicobacter pylori-bullfrog ferritin nanoparticles as an antigen delivery system. RBD-ferritin protein purified from mammalian cells efficiently assembled into 24-mer nanoparticles. Sixteen- to 20-month-old ferrets were vaccinated with RBD-ferritin nanoparticles (RBD nanoparticles) by intramuscular or intranasal inoculation. All vaccinated ferrets with RBD nanoparticles produced potent neutralizing antibodies against SARS-CoV-2. Strikingly, vaccinated ferrets demonstrated efficient protection from SARS-CoV-2 challenge, showing no fever, body weight loss, or clinical symptoms. Furthermore, vaccinated ferrets showed rapid clearance of infectious virus in nasal washes and lungs as well as of viral RNA in respiratory organs. This study demonstrates that spike RBD-nanoparticles are an effective protein vaccine candidate against SARS-CoV-2.


Subject(s)
COVID-19/prevention & control , Nanoparticles/chemistry , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/metabolism , Viral Vaccines/therapeutic use , Angiotensin-Converting Enzyme 2/chemistry , Animals , Cellulose/chemistry , Coronavirus/immunology , Coronavirus/pathogenicity , Ferrets , Ferritins , SARS-CoV-2/immunology , Viral Vaccines/chemistry
11.
mBio ; 12(2)2021 03 02.
Article in English | MEDLINE | ID: covidwho-1115089

ABSTRACT

There are no approved vaccines against the life-threatening Middle East respiratory syndrome coronavirus (MERS-CoV). Attenuated vaccines have proven their potential to induce strong and long-lasting immune responses. We have previously described that severe acute respiratory syndrome coronavirus (SARS-CoV) envelope (E) protein is a virulence factor. Based on this knowledge, a collection of mutants carrying partial deletions spanning the C-terminal domain of the E protein (rMERS-CoV-E*) has been generated using a reverse genetics system. One of these mutants, MERS-CoV-E*Δ2in, was attenuated and provided full protection in a challenge with virulent MERS-CoV after a single immunization dose. The MERS-CoV-E*Δ2in mutant was stable as it maintained its attenuation after 16 passages in cell cultures and has been selected as a promising vaccine candidate.IMPORTANCE The emergence of the new highly pathogenic human coronavirus SARS-CoV-2 that has already infected more than 80 million persons, killing nearly two million of them, clearly indicates the need to design efficient and safe vaccines protecting from these coronaviruses. Modern vaccines can be derived from virus-host interaction research directed to the identification of signaling pathways essential for virus replication and for virus-induced pathogenesis, in order to learn how to attenuate these viruses and design vaccines. Using a reverse genetics system developed in our laboratory, an infectious cDNA clone of MERS-CoV was engineered. Using this cDNA, we sequentially deleted several predicted and conserved motifs within the envelope (E) protein of MERS-CoV, previously associated with the presence of virulence factors. The in vitro and in vivo evaluation of these deletion mutants highlighted the relevance of predicted linear motifs in viral pathogenesis. Two of them, an Atg8 protein binding motif (Atg8-BM), and a forkhead-associated binding motif (FHA-BM), when deleted, rendered an attenuated virus that was evaluated as a vaccine candidate, leading to full protection against challenge with a lethal dose of MERS-CoV. This approach can be extended to the engineering of vaccines protecting against the new pandemic SARS-CoV-2.


Subject(s)
Middle East Respiratory Syndrome Coronavirus/pathogenicity , COVID-19/immunology , COVID-19/prevention & control , Genetic Engineering/methods , Humans , Middle East Respiratory Syndrome Coronavirus/immunology , Vaccines, Attenuated/therapeutic use , Viral Vaccines/therapeutic use
12.
BMC Microbiol ; 21(1): 58, 2021 02 22.
Article in English | MEDLINE | ID: covidwho-1094025

ABSTRACT

BACKGROUND: A severe form of pneumonia, named coronavirus disease 2019 (COVID-19) by the World Health Organization is widespread on the whole world. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was proved to be the main agent of COVID-19. In the present study, we conducted an in depth analysis of the SARS-COV-2 nucleocapsid to identify potential targets that may allow identification of therapeutic targets. METHODS: The SARS-COV-2 N protein subcellular localization and physicochemical property was analyzed by PSORT II Prediction and ProtParam tool. Then SOPMA tool and swiss-model was applied to analyze the structure of N protein. Next, the biological function was explored by mass spectrometry analysis and flow cytometry. At last, its potential phosphorylation sites were analyzed by NetPhos3.1 Server and PROVEAN PROTEIN. RESULTS: SARS-COV-2 N protein composed of 419 aa, is a 45.6 kDa positively charged unstable hydrophobic protein. It has 91 and 49% similarity to SARS-CoV and MERS-CoV and is predicted to be predominantly a nuclear protein. It mainly contains random coil (55.13%) of which the tertiary structure was further determined with high reliability (95.76%). Cells transfected with SARS-COV-2 N protein usually show a G1/S phase block company with an increased expression of TUBA1C, TUBB6. At last, our analysis of SARS-COV-2 N protein predicted a total number of 12 phosphorylated sites and 9 potential protein kinases which would significantly affect SARS-COV-2 N protein function. CONCLUSION: In this study, we report the physicochemical properties, subcellular localization, and biological function of SARS-COV-2 N protein. The 12 phosphorylated sites and 9 potential protein kinase sites in SARS-COV-2 N protein may serve as promising targets for drug discovery and development for of a recombinant virus vaccine.


Subject(s)
COVID-19/virology , Nucleocapsid Proteins/metabolism , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Amino Acid Sequence , COVID-19/genetics , COVID-19/immunology , Genome, Viral/genetics , HCT116 Cells , Humans , Molecular Sequence Data , Nucleocapsid Proteins/chemistry , Nucleocapsid Proteins/genetics , Phosphorylation , Reproducibility of Results , SARS-CoV-2/genetics , Viral Vaccines/therapeutic use
14.
Hum Vaccin Immunother ; 16(12): 2913-2920, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-998188

ABSTRACT

Globally, researchers are undertaking significant efforts to design and develop effective vaccines, therapeutics, and antiviral drugs to curb the spread of coronavirus disease 2019 (COVID-19). Plants have been used for the production of vaccines, monoclonal antibodies, immunomodulatory proteins, drugs, and pharmaceuticals via molecular farming/transient expression system and are considered as bioreactors or factories for their bulk production. These biological products are stable, safe, effective, easily available, and affordable. Plant molecular farming could facilitate rapid production of biologics on an industrial scale, and has the potential to fulfill emergency demands, such as in the present situation of the COVID-19 pandemic. This article aims to describe the methodology and basics of plant biopharming, in addition to its prospective applications for developing effective vaccines and antibodies to counter COVID-19.


Subject(s)
Antibodies, Viral/therapeutic use , Biological Products/therapeutic use , COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Phytochemicals/therapeutic use , SARS-CoV-2 , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/therapeutic use , Antibodies, Viral/immunology , Antiviral Agents/immunology , Antiviral Agents/therapeutic use , Biological Products/immunology , COVID-19/immunology , COVID-19 Vaccines/immunology , Humans , Phytochemicals/immunology , Plants , SARS-CoV-2/immunology , Viral Vaccines/immunology , Viral Vaccines/therapeutic use
15.
Br J Biomed Sci ; 77(4): 168-184, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-975140

ABSTRACT

The COVID-19 disease is caused by the SARS-CoV-2 virus, which is highly infective within the human population. The virus is widely disseminated to almost every continent with over twenty-seven million infections and over ninety-thousand reported deaths attributed to COVID-19 disease. SARS-CoV-2 is a single stranded RNA virus, comprising three main viral proteins; membrane, spike and envelope. The clinical features of COVID-19 disease can be classified according to different degrees of severity, with some patients progressing to acute respiratory distress syndrome, which can be fatal. In addition, many infections are asymptomatic or only cause mild symptoms. As there is no specific treatment for COVID-19 there is considerable endeavour to raise a vaccine against SARS-CoV-2, in addition to engineering neutralizing antibody interventions. In the absence of an effective vaccine, movement controls of varying stringencies have been imposed. Whilst enforced lockdown measures have been effective, they may be less effective against the current strain of SARS-CoV-2, the G614 clade. Conversely, other mutations of the virus, such as the Δ382 variant could reduce the clinical relevance of infection. The front runners in the race to develop an effective vaccine focus on the SARS-Co-V-2 Spike protein. However, vaccines that produce a T-cell response to a wider range of SARS-Co-V-2 viral proteins, may be more effective. Population based studies that determine the level of innate immunity to SARS-CoV-2, from prior exposure to the virus or to other coronaviruses, will have important implications for government imposed movement control and the strategic delivery of vaccination programmes.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Pandemics , SARS-CoV-2/immunology , COVID-19/immunology , COVID-19/virology , Humans , SARS-CoV-2/pathogenicity , Viral Vaccines/therapeutic use
16.
N Engl J Med ; 383(20): 1920-1931, 2020 11 12.
Article in English | MEDLINE | ID: covidwho-971502

ABSTRACT

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein. METHODS: We conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 µg, 100 µg, or 250 µg. There were 15 participants in each dose group. RESULTS: After the first vaccination, antibody responses were higher with higher dose (day 29 enzyme-linked immunosorbent assay anti-S-2P antibody geometric mean titer [GMT], 40,227 in the 25-µg group, 109,209 in the 100-µg group, and 213,526 in the 250-µg group). After the second vaccination, the titers increased (day 57 GMT, 299,751, 782,719, and 1,192,154, respectively). After the second vaccination, serum-neutralizing activity was detected by two methods in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-µg dose group reported one or more severe adverse events. CONCLUSIONS: The mRNA-1273 vaccine induced anti-SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 ClinicalTrials.gov number, NCT04283461).


Subject(s)
Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , RNA, Messenger/immunology , Spike Glycoprotein, Coronavirus/immunology , Viral Vaccines/therapeutic use , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Antibody Formation , Betacoronavirus , COVID-19 , COVID-19 Vaccines , Female , Humans , Immunization, Secondary , Male , SARS-CoV-2 , T-Lymphocytes/immunology , Viral Vaccines/adverse effects , Young Adult
17.
Sci Rep ; 10(1): 21594, 2020 12 09.
Article in English | MEDLINE | ID: covidwho-966852

ABSTRACT

Present hopes to conquer the Covid-19 epidemic are largely based on the expectation of a rapid availability of vaccines. However, once vaccine production starts, it will probably take time before there is enough vaccine for everyone, evoking the question how to distribute it best. While present vaccination guidelines largely focus on individual-based factors, i.e. on the question to whom vaccines should be provided first, e.g. to risk groups or to individuals with a strong social-mixing tendency, here we ask if a strategic spatiotemporal distribution of vaccines, e.g. to prioritize certain cities, can help to increase the overall survival rate of a population subject to an epidemic disease. To this end, we propose a strategy for the distribution of vaccines in time and space, which sequentially prioritizes regions with the most new cases of infection during a certain time frame and compare it with the standard practice of distributing vaccines demographically. Using a simple statistical model we find that, for a locally well-mixed population, the proposed strategy strongly reduces the number of deaths (by about a factor of two for basic reproduction numbers of [Formula: see text] and by about 35% for [Formula: see text]). The proposed vaccine distribution strategy establishes the idea that prioritizing individuals not only regarding individual factors, such as their risk of spreading the disease, but also according to the region in which they live can help saving lives. The suggested vaccine distribution strategy can be tested in more detailed models in the future and might inspire discussions regarding the importance of spatiotemporal distribution rules for vaccination guidelines.


Subject(s)
COVID-19 , Models, Biological , Pandemics , SARS-CoV-2 , Vaccination , Viral Vaccines , COVID-19/mortality , COVID-19/prevention & control , Humans , Viral Vaccines/supply & distribution , Viral Vaccines/therapeutic use
18.
Cytokine Growth Factor Rev ; 58: 16-29, 2021 04.
Article in English | MEDLINE | ID: covidwho-950779

ABSTRACT

Infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) results in diverse outcomes. The symptoms appear to be more severe in males older than 65 and people with underlying health conditions; approximately one in five individuals could be at risk worldwide. The virus's sequence was rapidly established days after the first cases were reported and identified an RNA virus from the Coronaviridae family closely related to a Betacoronavirus virus found in bats in China. SARS-CoV-2 is the seventh coronavirus known to infect humans, and with the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS), the only ones to cause severe diseases. Lessons from these two previous outbreaks guided the identification of critical therapeutic targets such as the spike viral proteins promoting the virus's cellular entry through the angiotensin-converting enzyme 2 (ACE2) receptor expressed on the surface of multiple types of eukaryotic cells. Although several therapeutic agents are currently evaluated, none seems to provide a clear path for a cure. Also, various types of vaccines are developed in record time to address the urgency of efficient SARS-CoV-2 prevention. Currently, 58 vaccines are evaluated in clinical trials, including 11 in phase III, and 3 of them reported efficacy above 90 %. The results so far from the clinical trials suggest the availability of multiple effective vaccines within months.


Subject(s)
Antiviral Agents , COVID-19 Vaccines/therapeutic use , COVID-19/drug therapy , COVID-19/prevention & control , Molecular Targeted Therapy/methods , SARS-CoV-2/immunology , Angiotensin-Converting Enzyme 2/physiology , Antiviral Agents/isolation & purification , Antiviral Agents/therapeutic use , COVID-19/immunology , Drug Development/methods , Genome, Viral/physiology , Humans , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Viral Vaccines/therapeutic use
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