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3.
EBioMedicine ; 76: 103841, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1649699

ABSTRACT

Currently licensed COVID-19 vaccines are all designed for intramuscular (IM) immunization. However, vaccination today failed to prevent the virus infection through the upper respiratory tract, which is partially due to the absence of mucosal immunity activation. Despite the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, the next generation of COVID-19 vaccine is in demand and intranasal (IN) vaccination method has been demonstrated to be potent in inducing both mucosal and systemic immune responses. Presently, although not licensed, various IN vaccines against SARS-CoV-2 are under intensive investigation, with 12 candidates reaching clinical trials at different phases. In this review, we give a detailed description about current status of IN COVID-19 vaccines, including virus-vectored vaccines, recombinant subunit vaccines and live attenuated vaccines. The ongoing clinical trials for IN vaccines are highlighted. Additionally, the underlying mechanisms of mucosal immunity and potential mucosal adjuvants and nasal delivery devices are also summarized.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , SARS-CoV-2/immunology , Administration, Intranasal , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/immunology , Clinical Trials as Topic , Humans , Immunity, Mucosal , SARS-CoV-2/isolation & purification , Viral Vaccines/administration & dosage , Viral Vaccines/immunology
4.
Biochemistry ; 60(46): 3449-3451, 2021 11 23.
Article in English | MEDLINE | ID: covidwho-1590174

ABSTRACT

Single-particle cryogenic electron microscopy (cryo-EM), whose full power was not realized until the advent of powerful detectors in 2012, has a unique position as a method of structure determination as it is capable of providing information about not only the structure but also the dynamical features of biomolecules. This information is of special importance in understanding virus-host interaction and explains the crucial role of cryo-EM in the efforts to find vaccinations and cures for pandemics the world has experienced in the past decade.


Subject(s)
Cryoelectron Microscopy , Host Microbial Interactions , Single Molecule Imaging , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Dengue/epidemiology , Dengue/prevention & control , Dengue/virology , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/prevention & control , Hemorrhagic Fever, Ebola/virology , Humans , Pandemics/prevention & control , Viral Vaccines/administration & dosage , Zika Virus Infection/epidemiology , Zika Virus Infection/prevention & control , Zika Virus Infection/virology
5.
Front Cell Infect Microbiol ; 10: 596166, 2020.
Article in English | MEDLINE | ID: covidwho-1574497

ABSTRACT

Viral infections continue to cause considerable morbidity and mortality around the world. Recent rises in these infections are likely due to complex and multifactorial external drivers, including climate change, the increased mobility of people and goods and rapid demographic change to name but a few. In parallel with these external factors, we are gaining a better understanding of the internal factors associated with viral immunity. Increasingly the gastrointestinal (GI) microbiome has been shown to be a significant player in the host immune system, acting as a key regulator of immunity and host defense mechanisms. An increasing body of evidence indicates that disruption of the homeostasis between the GI microbiome and the host immune system can adversely impact viral immunity. This review aims to shed light on our understanding of how host-microbiota interactions shape the immune system, including early life factors, antibiotic exposure, immunosenescence, diet and inflammatory diseases. We also discuss the evidence base for how host commensal organisms and microbiome therapeutics can impact the prevention and/or treatment of viral infections, such as viral gastroenteritis, viral hepatitis, human immunodeficiency virus (HIV), human papilloma virus (HPV), viral upper respiratory tract infections (URTI), influenza and SARS CoV-2. The interplay between the gastrointestinal microbiome, invasive viruses and host physiology is complex and yet to be fully characterized, but increasingly the evidence shows that the microbiome can have an impact on viral disease outcomes. While the current evidence base is informative, further well designed human clinical trials will be needed to fully understand the array of immunological mechanisms underlying this intricate relationship.


Subject(s)
Dysbiosis/virology , Microbiota/immunology , Probiotics/therapeutic use , Virus Diseases/immunology , Virus Diseases/microbiology , Animals , COVID-19/immunology , Dysbiosis/immunology , Gastrointestinal Microbiome/immunology , Host Microbial Interactions , Humans , SARS-CoV-2/isolation & purification , Viral Vaccines/administration & dosage , Viral Vaccines/immunology
6.
J Virol ; 96(3): e0150421, 2022 02 09.
Article in English | MEDLINE | ID: covidwho-1546442

ABSTRACT

In the age of COVID, nucleic acid vaccines have garnered much attention, at least in part, because of the simplicity of construction, production, and flexibility to adjust and adapt to an evolving outbreak. Orthopoxviruses remain a threat on multiple fronts, especially as emerging zoonoses. In response, we developed a DNA vaccine, termed 4pox, that protected nonhuman primates against monkeypox virus (MPXV)-induced severe disease. Here, we examined the protective efficacy of the 4pox DNA vaccine delivered by intramuscular (i.m.) electroporation (EP) in rabbits challenged with aerosolized rabbitpox virus (RPXV), a model that recapitulates the respiratory route of exposure and low dose associated with natural smallpox exposure in humans. We found that 4pox-vaccinated rabbits developed immunogen-specific antibodies, including neutralizing antibodies, and did not develop any clinical disease, indicating protection against aerosolized RPXV. In contrast, unvaccinated animals developed significant signs of disease, including lesions, and were euthanized. These findings demonstrate that an unformulated, nonadjuvanted DNA vaccine delivered i.m. can protect against an aerosol exposure. IMPORTANCE The eradication of smallpox and subsequent cessation of vaccination have left a majority of the population susceptible to variola virus or other emerging poxviruses. This is exemplified by human monkeypox, as evidenced by the increase in reported endemic and imported cases over the past decades. Therefore, a malleable vaccine technology that can be mass produced and does not require complex conditions for distribution and storage is sought. Herein, we show that a DNA vaccine, in the absence of a specialized formulation or adjuvant, can protect against a lethal aerosol insult of rabbitpox virus.


Subject(s)
/immunology , Orthopoxvirus/immunology , Poxviridae Infections/prevention & control , Vaccinia virus/immunology , Vaccinia/prevention & control , Viral Proteins/immunology , Viral Vaccines/immunology , Animals , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Dose-Response Relationship, Immunologic , Electroporation , Female , Immunization/methods , Immunogenicity, Vaccine , Lymphocyte Activation/immunology , Oligodeoxyribonucleotides/administration & dosage , Oligodeoxyribonucleotides/immunology , Rabbits , Vaccines, DNA/immunology , Vaccinia virus/genetics , Viral Vaccines/administration & dosage
7.
Biomed Pharmacother ; 144: 112282, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1517062

ABSTRACT

Six months after the publication of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) sequence, a record number of vaccine candidates were listed, and quite a number of them have since been approved for emergency use against the novel coronavirus disease 2019 (COVID-19). This unprecedented pharmaceutical feat did not only show commitment, creativity and collaboration of the scientific community, but also provided a swift solution that prevented global healthcare system breakdown. Notwithstanding, the available data show that most of the approved COVID-19 vaccines protect only a proportion of recipients against severe disease but do not prevent clinical manifestation of COVID-19. There is therefore the need to probe further to establish whether these vaccines can induce sterilizing immunity, otherwise, COVID-19 vaccination would have to become a regular phenomenon. The emergence of SARS-CoV-2 variants could further affect the capability of the available COVID-19 vaccines to prevent infection and protect recipients from a severe form of the disease. These notwithstanding, data about which vaccine(s), if any, can confer sterilizing immunity are unavailable. Here, we discuss the immune responses to viral infection with emphasis on COVID-19, and the specific adaptive immune response to SARS-CoV-2 and how it can be harnessed to develop COVID-19 vaccines capable of conferring sterilizing immunity. We further propose factors that could be considered in the development of COVID-19 vaccines capable of stimulating sterilizing immunity. Also, an old, but effective vaccine development technology that can be applied in the development of COVID-19 vaccines with sterilizing immunity potential is reviewed.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , T-Lymphocytes, Helper-Inducer/immunology , COVID-19 Vaccines/administration & dosage , Humans , SARS-CoV-2/drug effects , T-Lymphocytes, Helper-Inducer/drug effects , Viral Vaccines/administration & dosage , Viral Vaccines/immunology
9.
Proc Natl Acad Sci U S A ; 118(43)2021 10 26.
Article in English | MEDLINE | ID: covidwho-1481965

ABSTRACT

Self-amplifying RNA replicons are promising platforms for vaccine generation. Their defects in one or more essential functions for viral replication, particle assembly, or dissemination make them highly safe as vaccines. We previously showed that the deletion of the envelope (E) gene from the Middle East respiratory syndrome coronavirus (MERS-CoV) produces a replication-competent propagation-defective RNA replicon (MERS-CoV-ΔE). Evaluation of this replicon in mice expressing human dipeptidyl peptidase 4, the virus receptor, showed that the single deletion of the E gene generated an attenuated mutant. The combined deletion of the E gene with accessory open reading frames (ORFs) 3, 4a, 4b, and 5 resulted in a highly attenuated propagation-defective RNA replicon (MERS-CoV-Δ[3,4a,4b,5,E]). This RNA replicon induced sterilizing immunity in mice after challenge with a lethal dose of a virulent MERS-CoV, as no histopathological damage or infectious virus was detected in the lungs of challenged mice. The four mutants lacking the E gene were genetically stable, did not recombine with the E gene provided in trans during their passage in cell culture, and showed a propagation-defective phenotype in vivo. In addition, immunization with MERS-CoV-Δ[3,4a,4b,5,E] induced significant levels of neutralizing antibodies, indicating that MERS-CoV RNA replicons are highly safe and promising vaccine candidates.


Subject(s)
Coronavirus Infections/prevention & control , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/immunology , RNA, Viral/administration & dosage , Replicon , Viral Vaccines/administration & dosage , Animals , Antibodies, Neutralizing/biosynthesis , Antibodies, Viral/biosynthesis , Coronavirus Infections/genetics , Coronavirus Infections/immunology , Coronavirus Infections/virology , Defective Viruses/genetics , Defective Viruses/immunology , Female , Gene Deletion , Genes, env , Humans , Mice , Mice, Inbred C57BL , Mice, Transgenic , Middle East Respiratory Syndrome Coronavirus/pathogenicity , RNA, Viral/genetics , RNA, Viral/immunology , Vaccines, DNA , Vaccines, Virus-Like Particle/administration & dosage , Vaccines, Virus-Like Particle/genetics , Vaccines, Virus-Like Particle/immunology , Viral Vaccines/genetics , Viral Vaccines/immunology , Virulence/genetics , Virulence/immunology
11.
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
12.
Nat Commun ; 12(1): 4636, 2021 07 30.
Article in English | MEDLINE | ID: covidwho-1347938

ABSTRACT

Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that causes swift outbreaks. Major concerns are the persistent and disabling polyarthralgia in infected individuals. Here we present the results from a first-in-human trial of the candidate simian adenovirus vectored vaccine ChAdOx1 Chik, expressing the CHIKV full-length structural polyprotein (Capsid, E3, E2, 6k and E1). 24 adult healthy volunteers aged 18-50 years, were recruited in a dose escalation, open-label, nonrandomized and uncontrolled phase 1 trial (registry NCT03590392). Participants received a single intramuscular injection of ChAdOx1 Chik at one of the three preestablished dosages and were followed-up for 6 months. The primary objective was to assess safety and tolerability of ChAdOx1 Chik. The secondary objective was to assess the humoral and cellular immunogenicity. ChAdOx1 Chik was safe at all doses tested with no serious adverse reactions reported. The vast majority of solicited adverse events were mild or moderate, and self-limiting in nature. A single dose induced IgG and T-cell responses against the CHIKV structural antigens. Broadly neutralizing antibodies against the four CHIKV lineages were found in all participants and as early as 2 weeks after vaccination. In summary, ChAdOx1 Chik showed excellent safety, tolerability and 100% PRNT50 seroconversion after a single dose.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Chikungunya Fever/immunology , Chikungunya virus/immunology , Viral Vaccines/immunology , Adolescent , Adult , Chikungunya Fever/prevention & control , Chikungunya Fever/virology , Chikungunya virus/classification , Chikungunya virus/physiology , Cytokines/immunology , Cytokines/metabolism , Enzyme-Linked Immunosorbent Assay , Fatigue/chemically induced , Female , Headache/chemically induced , Humans , Immunoglobulin G/immunology , Injections, Intramuscular , Male , Middle Aged , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Vaccination/methods , Viral Vaccines/administration & dosage , Viral Vaccines/adverse effects , Young Adult
13.
Drug Deliv Transl Res ; 11(3): 748-787, 2021 06.
Article in English | MEDLINE | ID: covidwho-1343054

ABSTRACT

The host immune system is highly compromised in case of viral infections and relapses are very common. The capacity of the virus to destroy the host cell by liberating its own DNA or RNA and replicating inside the host cell poses challenges in the development of antiviral therapeutics. In recent years, many new technologies have been explored for diagnosis, prevention, and treatment of viral infections. Nanotechnology has emerged as one of the most promising technologies on account of its ability to deal with viral diseases in an effective manner, addressing the limitations of traditional antiviral medicines. It has not only helped us to overcome problems related to solubility and toxicity of drugs, but also imparted unique properties to drugs, which in turn has increased their potency and selectivity toward viral cells against the host cells. The initial part of the paper focuses on some important proteins of influenza, Ebola, HIV, herpes, Zika, dengue, and corona virus and those of the host cells important for their entry and replication into the host cells. This is followed by different types of nanomaterials which have served as delivery vehicles for the antiviral drugs. It includes various lipid-based, polymer-based, lipid-polymer hybrid-based, carbon-based, inorganic metal-based, surface-modified, and stimuli-sensitive nanomaterials and their application in antiviral therapeutics. The authors also highlight newer promising treatment approaches like nanotraps, nanorobots, nanobubbles, nanofibers, nanodiamonds, nanovaccines, and mathematical modeling for the future. The paper has been updated with the recent developments in nanotechnology-based approaches in view of the ongoing pandemic of COVID-19.Graphical abstract.


Subject(s)
Antiviral Agents/administration & dosage , Drug Carriers , Nanomedicine , Nanoparticles , Polymers/chemistry , Vaccination , Viral Vaccines/administration & dosage , Virus Diseases/prevention & control , Antiviral Agents/chemistry , COVID-19 Vaccines/administration & dosage , Drug Compounding , Humans , Viral Vaccines/chemistry , Virus Diseases/immunology , Virus Diseases/virology
14.
Viruses ; 13(7)2021 06 23.
Article in English | MEDLINE | ID: covidwho-1289015

ABSTRACT

A 59-year-old male with follicular lymphoma treated by anti-CD20-mediated B-cell depletion and ablative chemotherapy was hospitalized with a COVID-19 infection. Although the patient did not develop specific humoral immunity, he had a mild clinical course overall. The failure of all therapeutic options allowed infection to persist nearly 300 days with active accumulation of SARS-CoV-2 virus mutations. As a rescue therapy, an infusion of REGEN-COV (10933 and 10987) anti-spike monoclonal antibodies was performed 270 days from initial diagnosis. Due to partial clearance after the first dose (2.4 g), a consolidation dose (8 g) was infused six weeks later. Complete virus clearance could then be observed over the following month, after he was vaccinated with the Pfizer-BioNTech anti-COVID-19 vaccination. The successful management of this patient required prolonged enhanced quarantine, monitoring of virus mutations, pioneering clinical decisions based upon close consultation, and the coordination of multidisciplinary experts in virology, immunology, pharmacology, input from REGN, the FDA, the IRB, the health care team, the patient, and the patient's family. Current decisions to take revolve around patient's follicular lymphoma management, and monitoring for virus clearance persistence beyond disappearance of REGEN-COV monoclonal antibodies after anti-SARS-CoV-2 vaccination. Overall, specific guidelines for similar cases should be established.


Subject(s)
Antibodies, Monoclonal/therapeutic use , B-Lymphocytes/immunology , COVID-19/immunology , COVID-19/therapy , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , COVID-19/complications , Humans , Immunity, Humoral , Lymphocyte Depletion , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/therapy , Male , Middle Aged , SARS-CoV-2/genetics , Viral Vaccines/administration & dosage , Viral Vaccines/immunology
15.
Int J Mol Sci ; 22(13)2021 Jun 28.
Article in English | MEDLINE | ID: covidwho-1288899

ABSTRACT

Viral-associated respiratory infectious diseases are one of the most prominent subsets of respiratory failures, known as viral respiratory infections (VRI). VRIs are proceeded by an infection caused by viruses infecting the respiratory system. For the past 100 years, viral associated respiratory epidemics have been the most common cause of infectious disease worldwide. Due to several drawbacks of the current anti-viral treatments, such as drug resistance generation and non-targeting of viral proteins, the development of novel nanotherapeutic or nano-vaccine strategies can be considered essential. Due to their specific physical and biological properties, nanoparticles hold promising opportunities for both anti-viral treatments and vaccines against viral infections. Besides the specific physiological properties of the respiratory system, there is a significant demand for utilizing nano-designs in the production of vaccines or antiviral agents for airway-localized administration. SARS-CoV-2, as an immediate example of respiratory viruses, is an enveloped, positive-sense, single-stranded RNA virus belonging to the coronaviridae family. COVID-19 can lead to acute respiratory distress syndrome, similarly to other members of the coronaviridae. Hence, reviewing the current and past emerging nanotechnology-based medications on similar respiratory viral diseases can identify pathways towards generating novel SARS-CoV-2 nanotherapeutics and/or nano-vaccines.


Subject(s)
Antiviral Agents/chemistry , Drug Carriers/chemistry , Nanomedicine , Respiratory Tract Infections/pathology , Viral Vaccines/chemistry , Virus Diseases/pathology , Antiviral Agents/therapeutic use , COVID-19/immunology , COVID-19/pathology , COVID-19/therapy , COVID-19/virology , Humans , Immune System/metabolism , Respiratory Tract Infections/therapy , Respiratory Tract Infections/virology , SARS-CoV-2/isolation & purification , Viral Vaccines/administration & dosage , Viral Vaccines/immunology , Virus Diseases/immunology , Virus Diseases/prevention & control , Virus Diseases/therapy
16.
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
17.
Adv Sci (Weinh) ; 8(16): e2100985, 2021 08.
Article in English | MEDLINE | ID: covidwho-1281196

ABSTRACT

COVID-19 is disastrous to global health and the economy. SARS-CoV-2 infection exhibits similar clinical symptoms and immunopathological sequelae to SARS-CoV infection. Therefore, much of the developmental progress on SARS-CoV vaccines can be utilized for the development of SARS-CoV-2 vaccines. Careful antigen selection during development is always of utmost importance for the production of effective vaccines that do not compromise recipient safety. This holds especially true for SARS-CoV vaccines, as several immunopathological disorders are associated with the activity of structural and nonstructural proteins encoded in the virus's genetic material. Whole viral protein and RNA-encoding full-length proteins contain both protective and "dangerous" sequences, unless pathological fragments are deleted. In light of recent advances, peptide vaccines may present a very safe and effective alternative. Peptide vaccines can avoid immunopathological pro-inflammatory sequences, focus immune responses on neutralizing immunogenic epitopes, avoid off-target antigen loss, combine antigens with different protective roles or mechanisms, even from different viral proteins, and avoid mutant escape by employing highly conserved cryptic epitopes. In this review, an attempt is made to exploit the similarities between SARS-CoV and SARS-CoV-2 in vaccine antigen screening, with particular attention to the pathological and immunogenic properties of SARS proteins.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Viral Vaccines/immunology , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Humans , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Subunit/administration & dosage , Vaccines, Subunit/immunology , Viral Vaccines/administration & dosage
18.
J Virol ; 95(17): e0066721, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1274527

ABSTRACT

Cellular immune responses play a key role in the control of viral infection. The nucleocapsid (N) protein of infectious bronchitis virus (IBV) is a major immunogenic protein that can induce protective immunity. To screen for potential T-cell epitopes on IBV N protein, 40 overlapping peptides covering the entirety of the N protein were designed and synthesized. Four T-cell epitope peptides were identified by gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISpot), intracellular cytokine staining, and carboxyfluorescein succinimidyl ester (CFSE) lymphocyte proliferation assays; among them, three peptides (N211-230, N271-290, and N381-400) were cytotoxic T lymphocyte (CTL) epitopes, and one peptide (N261-280) was a dual-specific T-cell epitope, which can be recognized by both CD8+ and CD4+ T cells. Multi-epitope gene transcription cassettes comprising four neutralizing epitope domains and four T-cell epitope peptides were synthesized and inserted into the genome of Newcastle disease virus strain La Sota between the P and M genes. Recombinant IBV multi-epitope vaccine candidate rLa Sota/SBNT was generated via reverse genetics, and its immune protection efficacy was evaluated in specific-pathogen-free chickens. Our results show that rLa Sota/SBNT induced IBV-specific neutralizing antibody and T-cell responses and provided significant protection against homologous and heterologous IBV challenge. Thus, the T-cell epitope peptides identified in this study could be good candidates for IBV vaccine development, and recombinant Newcastle disease virus-expressing IBV multi-epitope genes represent a safe and effective vaccine candidate for controlling infectious bronchitis. IMPORTANCE T-cell-mediated immune responses are critical for the elimination of IBV-infected cells. To screen conserved T-cell epitopes in the IBV N protein, 40 overlapping peptides covering the entirety of the N protein were designed and synthesized. By combining IFN-γ ELISpot, intracellular cytokine staining, and CFSE lymphocyte proliferation assays, we identified three CTL epitopes and one dual-specific T-cell epitope. The value of T-cell epitope peptides identified in the N protein was further verified by the design of an IBV multi-epitope vaccine. Results show that IBV multi-epitope vaccine candidate rLa Sota/SBNT provided cross protection against challenges with a QX-like or a TW-like IBV strain. So, T-cell-mediated immune responses play an important role in the control of viral infection, and conserved T-cell epitopes serve as promising candidates for use in multi-epitope vaccine construction. Our results provide a new perspective for the development of a safer and more effective IBV vaccine.


Subject(s)
Coronavirus Infections/prevention & control , Epitopes, T-Lymphocyte/immunology , Immunity, Cellular/immunology , Infectious bronchitis virus/immunology , Nucleocapsid Proteins/immunology , Poultry Diseases/prevention & control , Viral Vaccines/administration & dosage , Animals , Chickens , Coronavirus Infections/immunology , Coronavirus Infections/virology , Immunity, Cellular/drug effects , Poultry Diseases/immunology , Specific Pathogen-Free Organisms , T-Lymphocytes, Cytotoxic/immunology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunology , Viral Vaccines/immunology
19.
Asian Pac J Allergy Immunol ; 38(3): 150-161, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1231595

ABSTRACT

SARS-CoV-2 had already killed more than 400,000 patients around the world according to data on 7 June 2020. Bacillus Calmette-Guérin (BCG) vaccine is developed from live-attenuated Mycobacterium bovis, which is a microorganism found in a cow. Discovered by Dr. Albert Calmette and Camille Guérin since 1921, the BCG has served as a protection against tuberculosis and its complications. It is noticeable that countries which use mandatory BCG vaccination approach had lower COVID-19 infection and death rate. Current review aims to clarify this issue through epidemiological illustration of correlation between national BCG immunization and COVID-19 mortality, in addition to biological background of BCG-induced immunity Epidemiological data shows that universal BCG policy countries have lower median mortality rate compare to countries with past universal BCG policy and non-mass immunization BCG. (18 May 2020). Still, the links between BCG vaccination and better COVID-19 situation in certain countries are unclear, and more data on actual infection rate using SAR-CoV-2 antibody testing in large population sample is crucial for disease spreading comparison. Two immunological mechanisms, heterologous effects of adaptive immunity and trained innate immunity which induced by BCG vaccination, may explain host tolerance against COVID-19 infection, however, there is no direct evidence to support this biological background. Clinical trials related to BCG vaccination against COVID-19 are under investigation. Without a strong evidence, BCG must not be recommended for COVID-19 prevention, although, this should not be absolute contraindication. Risk of local and systemic complications from the vaccine should be informed to individual, who request BCG immunization.


Subject(s)
BCG Vaccine/administration & dosage , Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Vaccination , Viral Vaccines/administration & dosage , Adaptive Immunity , BCG Vaccine/adverse effects , BCG Vaccine/immunology , COVID-19 , COVID-19 Vaccines , Cause of Death , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Coronavirus Infections/virology , Host-Pathogen Interactions , Humans , Immunity, Innate , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , SARS-CoV-2 , Treatment Outcome , Vaccination/adverse effects , Viral Vaccines/adverse effects , Viral Vaccines/immunology
20.
Math Biosci ; 337: 108621, 2021 07.
Article in English | MEDLINE | ID: covidwho-1207058

ABSTRACT

When allocating limited vaccines to control an infectious disease, policy makers frequently have goals relating to individual health benefits (e.g., reduced morbidity and mortality) as well as population-level health benefits (e.g., reduced transmission and possible disease eradication). We consider the optimal allocation of a limited supply of a preventive vaccine to control an infectious disease, and four different allocation objectives: minimize new infections, deaths, life years lost, or quality-adjusted life years (QALYs) lost due to death. We consider an SIR model with n interacting populations, and a single allocation of vaccine at time 0. We approximate the model dynamics to develop simple analytical conditions characterizing the optimal vaccine allocation for each objective. We instantiate the model for an epidemic similar to COVID-19 and consider n=2 population groups: one group (individuals under age 65) with high transmission but low mortality and the other group (individuals age 65 or older) with low transmission but high mortality. We find that it is optimal to vaccinate younger individuals to minimize new infections, whereas it is optimal to vaccinate older individuals to minimize deaths, life years lost, or QALYs lost due to death. Numerical simulations show that the allocations resulting from our conditions match those found using much more computationally expensive algorithms such as exhaustive search. Sensitivity analysis on key parameters indicates that the optimal allocation is robust to changes in parameter values. The simple conditions we develop provide a useful means of informing vaccine allocation decisions for communicable diseases.


Subject(s)
Epidemics/prevention & control , Mass Vaccination , Models, Theoretical , Viral Vaccines , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19/prevention & control , Humans , Mass Vaccination/methods , Mass Vaccination/standards , Middle Aged , Viral Vaccines/administration & dosage , Viral Vaccines/supply & distribution , Young Adult
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