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1.
Can Vet J ; 65(6): 581-586, 2024 Jun.
Article En | MEDLINE | ID: mdl-38827595

Objective: Bovine respiratory disease (BRD) and overall postweaning treatment rates were compared among 3 groups of calves either differentially primed and boosted with commercially available bovine coronavirus (BCoV) vaccine or not vaccinated against BCoV. Animals: Commercial heifer and steer beef calves born in April and May 2022. Procedure: In June 2022, calves were randomly enrolled into 3 treatment groups. Those in 2 groups [V1 (n = 160) and V2 (n = 160)] were administered a mucosal priming dose of 1 of 2 commercial BCoV vaccines; those in the 3rd group [CTL (n = 151)] were unvaccinated against BCoV. The V1 and V2 groups were boosted by intramuscular injection pre-weaning with the same vaccine used for priming. Weaning occurred 3 wk after the last preweaning processing day. Ranch staff used a BRD case definition provided by their herd veterinarian to identify, treat, and record treatments for 45 d post-weaning. Results: Postweaning BRD treatment rates for V1, V2, and CTL were 7%, 9%, and 14%, respectively. The CTL calves had 2.2× greater odds of receiving treatment for BRD than V1 calves. There were no differences in odds of treatment between CTL and V2 calves or V1 and V2 calves. Conclusion: In a herd with previously diagnosed BCoV BRD cases, prime-boost vaccination of calves is associated with a difference in odds of BRD treatment post-weaning compared to not vaccinating calves against BCoV. Clinical relevance: Prime-boost vaccination with commercial BCoV vaccine may be an important management tool for herds with known BCoV BRD outbreaks.


Comparaison des taux de traitement des maladies respiratoires bovines après le sevrage entre des veaux de boucherie témoins non vaccinés et des veaux vaccinés amorce-rappel de manière variable à l'aide de vaccins contre le coronavirus bovin commercialement disponibles. Objectif: La maladie respiratoire bovine (BRD) et les taux globaux de traitement post-sevrage ont été comparés parmi 3 groupes de veaux soit vaccinés de manière différentielle et avec un rappel avec le vaccin contre le coronavirus bovin (BCoV) disponible commercialement, soit non vaccinés contre le BCoV. Animaux: Génisses et veaux de boucherie commerciaux nés en avril et mai 2022. Procédure: En juin 2022, les veaux ont été randomisés lors du recrutement dans 3 groupes de traitement. Ceux des 2 groupes [V1 (n = 160) et V2 (n = 160)] ont reçu une dose d'amorce par voie muqueuse de l'un des deux vaccins commerciaux BCoV; ceux du 3ème groupe [CTL (n = 151)] n'étaient pas vaccinés contre le BCoV. Les groupes V1 et V2 ont eu un rappel par injection intramusculaire avant le sevrage avec le même vaccin que celui utilisé pour l'amorçage. Le sevrage a eu lieu 3 semaines après le dernier jour de conditionnement pré-sevrage. Le personnel du ranch a utilisé une définition de cas de BRD fournie par le vétérinaire de leur troupeau pour identifier, traiter et enregistrer les traitements pendant 45 jours après le sevrage. Résultats: Les taux de traitement BRD post-sevrage pour V1, V2 et CTL étaient respectivement de 7 %, 9 % et 14 %. Les veaux CTL avaient 2,2 fois plus de chances de recevoir un traitement contre la BRD que les veaux V1. Il n'y avait aucune différence dans les probabilités de traitement entre les veaux CTL et V2 ou entre les veaux V1 et V2. Conclusion: Dans un troupeau avec des cas de BRD causés par le BCoV déjà diagnostiqués, la vaccination amorce-rappel des veaux est associée à une différence de probabilité de traitement par le BRD après le sevrage par rapport à la nonvaccination des veaux contre le BCoV. Pertinence clinique: La vaccination amorce-rappel avec le vaccin commercial BCoV peut être un outil de gestion important pour les troupeaux présentant des foyers connus de BCoV BRD.(Traduit par Dr Serge Messier).


Coronavirus, Bovine , Viral Vaccines , Animals , Cattle , Viral Vaccines/administration & dosage , Viral Vaccines/immunology , Coronavirus, Bovine/immunology , Male , Female , Coronavirus Infections/veterinary , Coronavirus Infections/prevention & control , Weaning , Vaccination/veterinary , Bovine Respiratory Disease Complex/prevention & control
2.
Front Public Health ; 12: 1386495, 2024.
Article En | MEDLINE | ID: mdl-38827618

Introduction: Mitigating the spread of infectious diseases is of paramount concern for societal safety, necessitating the development of effective intervention measures. Epidemic simulation is widely used to evaluate the efficacy of such measures, but realistic simulation environments are crucial for meaningful insights. Despite the common use of contact-tracing data to construct realistic networks, they have inherent limitations. This study explores reconstructing simulation networks using link prediction methods as an alternative approach. Methods: The primary objective of this study is to assess the effectiveness of intervention measures on the reconstructed network, focusing on the 2015 MERS-CoV outbreak in South Korea. Contact-tracing data were acquired, and simulation networks were reconstructed using the graph autoencoder (GAE)-based link prediction method. A scale-free (SF) network was employed for comparison purposes. Epidemic simulations were conducted to evaluate three intervention strategies: Mass Quarantine (MQ), Isolation, and Isolation combined with Acquaintance Quarantine (AQ + Isolation). Results: Simulation results showed that AQ + Isolation was the most effective intervention on the GAE network, resulting in consistent epidemic curves due to high clustering coefficients. Conversely, MQ and AQ + Isolation were highly effective on the SF network, attributed to its low clustering coefficient and intervention sensitivity. Isolation alone exhibited reduced effectiveness. These findings emphasize the significant impact of network structure on intervention outcomes and suggest a potential overestimation of effectiveness in SF networks. Additionally, they highlight the complementary use of link prediction methods. Discussion: This innovative methodology provides inspiration for enhancing simulation environments in future endeavors. It also offers valuable insights for informing public health decision-making processes, emphasizing the importance of realistic simulation environments and the potential of link prediction methods.


Contact Tracing , Coronavirus Infections , Disease Outbreaks , Middle East Respiratory Syndrome Coronavirus , Humans , Republic of Korea/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/prevention & control , Coronavirus Infections/epidemiology , Contact Tracing/methods , Disease Outbreaks/prevention & control , Quarantine , Computer Simulation
3.
Med Microbiol Immunol ; 213(1): 6, 2024 May 09.
Article En | MEDLINE | ID: mdl-38722338

To date, there is no licensed vaccine for Middle East respiratory syndrome coronavirus (MERS-CoV). Therefore, MERS-CoV is one of the diseases targeted by the Coalition for Epidemic Preparedness Innovations (CEPI) vaccine development programs and has been classified as a priority disease by the World Health Organization (WHO). An important measure of vaccine immunogenicity and antibody functionality is the detection of virus-neutralizing antibodies. We have developed and optimized a microneutralization assay (MNA) using authentic MERS-CoV and standardized automatic counting of virus foci. Compared to our standard virus neutralization assay, the MNA showed improved sensitivity when analyzing 30 human sera with good correlation of results (Spearman's correlation coefficient r = 0.8917, p value < 0.0001). It is important to use standardized materials, such as the WHO international standard (IS) for anti-MERS-CoV immunoglobulin G, to compare the results from clinical trials worldwide. Therefore, in addition to the neutralizing titers (NT50 = 1384, NT80 = 384), we determined the IC50 and IC80 of WHO IS in our MNA to be 0.67 IU/ml and 2.6 IU/ml, respectively. Overall, the established MNA is well suited to reliably quantify vaccine-induced neutralizing antibodies with high sensitivity.


Antibodies, Neutralizing , Antibodies, Viral , Middle East Respiratory Syndrome Coronavirus , Neutralization Tests , Middle East Respiratory Syndrome Coronavirus/immunology , Humans , Neutralization Tests/methods , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Coronavirus Infections/prevention & control , Coronavirus Infections/immunology , Coronavirus Infections/diagnosis , Animals , Inhibitory Concentration 50 , Sensitivity and Specificity
4.
Med Sci (Basel) ; 12(2)2024 May 22.
Article En | MEDLINE | ID: mdl-38804384

mRNA vaccines have emerged as an optimistic technological platform for vaccine innovation in this new scientific era. mRNA vaccines have dramatically altered the domain of vaccinology by offering a versatile and rapid approach to combating infectious diseases and virus-induced cancers. Clinical trials have demonstrated efficacy rates of 94-95% in preventing COVID-19, and mRNA vaccines have been increasingly recognized as a powerful vaccine platform. Although mRNA vaccines have played an essential role in the COVID-19 pandemic, they still have several limitations; their instability and degradation affect their storage, delivery, and over-all efficiency. mRNA is typically enclosed in a transport mechanism to facilitate its entry into the target cell because it is an unstable and negatively charged molecule. For instance, mRNA that is given using lipid-nanoparticle-based vaccine delivery systems (LNPs) solely enters cells through endocytosis, establishing an endosome without damaging the cell membrane. The COVID-19 pandemic has accelerated the development of mRNA vaccine platforms used to treat and prevent several infectious diseases. This technology has the potential to change the future course of the disease by providing a safe and effective way to combat infectious diseases and cancer. A single-stranded genetic sequence found in mRNA vaccines instructs host cells to produce proteins inside ribosomes to elicit immunological responses and prepare the immune system to fight infections or cancer cells. The potential applications of mRNA vaccine technology are vast and can lead to the development of a preferred vaccine pattern. As a result, a new generation of vaccinations has gradually gained popularity and access to the general population. To adapt the design of an antigen, and even combine sequences from different variations in response to new changes in the viral genome, mRNA vaccines may be used. Current mRNA vaccines provide adequate safety and protection, but the duration of that protection can only be determined if further clinical research is conducted.


COVID-19 , SARS-CoV-2 , mRNA Vaccines , Humans , COVID-19/prevention & control , SARS-CoV-2/immunology , Pandemics/prevention & control , Oncogenic Viruses , Vaccines, Synthetic , Vaccine Development , COVID-19 Vaccines/immunology , Pneumonia, Viral/prevention & control , Coronavirus Infections/prevention & control , Betacoronavirus , Viral Vaccines/immunology , RNA, Messenger , Neoplasms
5.
Hum Vaccin Immunother ; 20(1): 2351664, 2024 Dec 31.
Article En | MEDLINE | ID: mdl-38757508

Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal beta-coronavirus that emerged in 2012. The virus is part of the WHO blueprint priority list with a concerning fatality rate of 35%. Scientific efforts are ongoing for the development of vaccines, anti-viral and biotherapeutics, which are majorly directed toward the structural spike protein. However, the ongoing effort is challenging due to conformational instability of the spike protein and the evasion strategy posed by the MERS-CoV. In this study, we have expressed and purified the MERS-CoV pre-fusion spike protein in the Expi293F mammalian expression system. The purified protein was extensively characterized for its biochemical and biophysical properties. Thermal stability analysis showed a melting temperature of 58°C and the protein resisted major structural changes at elevated temperature as revealed by fluorescence spectroscopy and circular dichroism. Immunological assessment of the MERS-CoV spike immunogen in BALB/c mice with AddaVaxTM and Imject alum adjuvants showed elicitation of high titer antibody responses but a more balanced Th1/Th2 response with AddaVaxTM squalene like adjuvant. Together, our results suggest the formation of higher-order trimeric pre-fusion MERS-CoV spike proteins, which were able to induce robust immune responses. The comprehensive characterization of MERS-CoV spike protein warrants a better understanding of MERS spike protein and future vaccine development efforts.


Antibodies, Viral , Mice, Inbred BALB C , Middle East Respiratory Syndrome Coronavirus , Spike Glycoprotein, Coronavirus , Viral Vaccines , Middle East Respiratory Syndrome Coronavirus/immunology , Animals , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/genetics , Antibodies, Viral/immunology , Antibodies, Viral/blood , Viral Vaccines/immunology , Mice , Female , Coronavirus Infections/prevention & control , Coronavirus Infections/immunology , Immunogenicity, Vaccine , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , Adjuvants, Immunologic/administration & dosage , Adjuvants, Vaccine , Humans
6.
Front Immunol ; 15: 1397118, 2024.
Article En | MEDLINE | ID: mdl-38812505

Porcine epidemic diarrhea virus (PEDV) causes a highly contagious enteric disease with major economic losses to swine production worldwide. Due to the immaturity of the neonatal piglet immune system and given the high virulence of PEDV, improving passive lactogenic immunity is the best approach to protect suckling piglets against the lethal infection. We tested whether oral vitamin A (VA) supplementation and PEDV exposure of gestating and lactating VA-deficient (VAD) sows would enhance their primary immune responses and boost passive lactogenic protection against the PEDV challenge of their piglets. We demonstrated that PEDV inoculation of pregnant VAD sows in the third trimester provided higher levels of lactogenic protection of piglets as demonstrated by >87% survival rates of their litters compared with <10% in mock litters and that VA supplementation to VAD sows further improved the piglets' survival rates to >98%. We observed significantly elevated PEDV IgA and IgG antibody (Ab) titers and Ab-secreting cells (ASCs) in VA-sufficient (VAS)+PEDV and VAD+VA+PEDV sows, with the latter maintaining higher Ab titers in blood prior to parturition and in blood and milk throughout lactation. The litters of VAD+VA+PEDV sows also had the highest serum PEDV-neutralizing Ab titers at piglet post-challenge days (PCD) 0 and 7, coinciding with higher PEDV IgA ASCs and Ab titers in the blood and milk of their sows, suggesting an immunomodulatory role of VA in sows. Thus, sows that delivered sufficient lactogenic immunity to their piglets provided the highest passive protection against the PEDV challenge. Maternal immunization during pregnancy (± VA) and VA sufficiency enhanced the sow primary immune responses, expression of gut-mammary gland trafficking molecules, and passive protection of their offspring. Our findings are relevant to understanding the role of VA in the Ab responses to oral attenuated vaccines that are critical for successful maternal vaccination programs against enteric infections in infants and young animals.


Adaptive Immunity , Antibodies, Viral , Coronavirus Infections , Immunity, Maternally-Acquired , Porcine epidemic diarrhea virus , Swine Diseases , Vitamin A , Animals , Porcine epidemic diarrhea virus/immunology , Female , Swine , Pregnancy , Vitamin A/administration & dosage , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Coronavirus Infections/veterinary , Coronavirus Infections/virology , Antibodies, Viral/blood , Swine Diseases/immunology , Swine Diseases/prevention & control , Swine Diseases/virology , Animals, Newborn , Lactation/immunology , Dietary Supplements , Vitamin A Deficiency/immunology , Immunization
7.
Hum Vaccin Immunother ; 20(1): 2346390, 2024 Dec 31.
Article En | MEDLINE | ID: mdl-38691025

Middle East respiratory coronavirus (MERS-CoV) is a newly emergent, highly pathogenic coronavirus that is associated with 34% mortality rate. MERS-CoV remains listed as priority pathogen by the WHO. Since its discovery in 2012 and despite the efforts to develop coronaviruses vaccines to fight against SARS-CoV-2, there are currently no MERS-CoV vaccine that has been approved. Therefore, there is high demand to continue on the development of prophylactic vaccines against MERS-CoV. Current advancements in vaccine developments can be adapted for the development of improved MERS-CoV vaccines candidates. Nucleic acid-based vaccines, including pDNA and mRNA, are relatively new class of vaccine platforms. In this work, we developed pDNA and mRNA vaccine candidates expressing S.FL gene of MERS-CoV. Further, we synthesized a silane functionalized hierarchical aluminosilicate to encapsulate each vaccine candidates. We tested the nucleic acid vaccine candidates in mice and evaluated humoral antibodies response. Interestingly, we determined that the non-encapsulated, codon optimized S.FL pDNA vaccine candidate elicited the highest level of antibody responses against S.FL and S1 of MERS-CoV. Encapsulation of mRNA with nanoporous aluminosilicate increased the humoral antibody responses, whereas encapsulation of pDNA did not. These findings suggests that MERS-CoV S.FL pDNA vaccine candidate induced the highest level of humoral responses. This study will enhance further optimization of nanosilica as potential carrier for mRNA vaccines. In conclusion, this study suggests MERS-CoV pDNA vaccine candidate as a suitable vaccine platform for further pivotal preclinical testings.


Antibodies, Viral , Coronavirus Infections , Middle East Respiratory Syndrome Coronavirus , Nanoparticles , Silicon Dioxide , Vaccines, DNA , Viral Vaccines , Animals , Vaccines, DNA/immunology , Vaccines, DNA/genetics , Vaccines, DNA/administration & dosage , Middle East Respiratory Syndrome Coronavirus/immunology , Middle East Respiratory Syndrome Coronavirus/genetics , Mice , Viral Vaccines/immunology , Viral Vaccines/genetics , Viral Vaccines/administration & dosage , Antibodies, Viral/immunology , Coronavirus Infections/prevention & control , Coronavirus Infections/immunology , Silicon Dioxide/chemistry , Mice, Inbred BALB C , Female , Humans , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/genetics , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , Vaccine Development
8.
ACS Nano ; 18(19): 12235-12260, 2024 May 14.
Article En | MEDLINE | ID: mdl-38696217

Variants of coronavirus porcine epidemic diarrhea virus (PEDV) frequently emerge, causing an incomplete match between the vaccine and variant strains, which affects vaccine efficacy. Designing vaccines with rapidly replaceable antigens and high efficacy is a promising strategy for the prevention of infection with PEDV variant strains. In our study, three different types of self-assembled nanoparticles (nps) targeting receptor-binding N-terminal domain (NTD) and C-terminal domain (CTD) of S1 protein, named NTDnps, CTDnps, and NTD/CTDnps, were constructed and evaluated as vaccine candidates against PEDV. NTDnps and CTDnps vaccines mediated significantly higher neutralizing antibody (NAb) titers than NTD and CTD recombinant proteins in mice. The NTD/CTDnps in varying ratios elicited significantly higher NAb titers when compared with NTDnps and CTDnps alone. The NTD/CTDnps (3:1) elicited NAb with titers up to 92.92% of those induced by the commercial vaccine. Piglets immunized with NTD/CTDnps (3:1) achieved a passive immune protection rate of 83.33% of that induced by the commercial vaccine. NTD/CTDnps (3:1) enhanced the capacity of mononuclear macrophages and dendritic cells to take up and present antigens by activating major histocompatibility complex I and II molecules to stimulate humoral and cellular immunity. These data reveal that a combination of S1-NTD and S1-CTD antigens targeting double receptor-binding domains strengthens the protective immunity of nanoparticle vaccines against PEDV. Our findings will provide a promising vaccine candidate against PEDV.


Nanoparticles , Porcine epidemic diarrhea virus , Viral Vaccines , Porcine epidemic diarrhea virus/immunology , Animals , Nanoparticles/chemistry , Swine , Mice , Viral Vaccines/immunology , Coronavirus Infections/prevention & control , Coronavirus Infections/immunology , Mice, Inbred BALB C , Antigens, Viral/immunology , Antigens, Viral/chemistry , Antibodies, Neutralizing/immunology , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/chemistry , Protein Domains/immunology , Female , Nanovaccines
10.
J Gen Virol ; 105(4)2024 Apr.
Article En | MEDLINE | ID: mdl-38656455

Porcine epidemic diarrhea (PED) is a serious disease in piglets that leads to high mortality. An effective measure that provides higher IgA levels in the intestine and milk is required to decrease losses. Porcine epidemic diarrhea virus (PEDV) was dissolved in calcium alginate (Alg) and combined with chitosan (CS) via electrostatic interactions between cationic chitosan and anionic alginate to create a porous gel (Alg-CS+PEDV). The gel was used to immunize mice orally or in combination with subcutaneous injections of inactivated PEDV vaccine. At 12 and 24 days after immunization, levels of IgA and IgG in Alg-CS+PEDV were higher than with normal PEDV oral administration. At 24 days after immunization, the concentration of IFN-γ in Alg-CS+PEDV was higher than with normal PEDV oral administration. Furthermore, oral administration combining subcutaneous immunization induced higher levels of IgG and IgA than oral administration alone. Our study provides a new method for the preparation and administration of oral vaccines to achieve enhanced mucosal immunity against PEDV.


Alginates , Antibodies, Viral , Chitosan , Immunity, Mucosal , Immunoglobulin A , Immunoglobulin G , Porcine epidemic diarrhea virus , Viral Vaccines , Animals , Administration, Oral , Porcine epidemic diarrhea virus/immunology , Alginates/administration & dosage , Chitosan/administration & dosage , Mice , Viral Vaccines/immunology , Viral Vaccines/administration & dosage , Antibodies, Viral/immunology , Immunoglobulin A/immunology , Immunoglobulin G/blood , Swine , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Coronavirus Infections/veterinary , Coronavirus Infections/virology , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/immunology , Swine Diseases/immunology , Swine Diseases/prevention & control , Swine Diseases/virology , Female , Gels/administration & dosage , Mice, Inbred BALB C , Interferon-gamma/immunology , Glucuronic Acid/administration & dosage , Hexuronic Acids/administration & dosage
12.
Int J Biol Macromol ; 267(Pt 1): 131427, 2024 May.
Article En | MEDLINE | ID: mdl-38583833

Due to the health emergency created by SARS-CoV-2, the virus that causes the COVID-19 disease, the rapid implementation of a new vaccine technology was necessary. mRNA vaccines, being one of the cutting-edge new technologies, attracted significant interest and offered a lot of hope. The potential of these vaccines in preventing admission to hospitals and serious illness in people with comorbidities has recently been called into question due to the vaccines' rapidly waning immunity. Mounting evidence indicates that these vaccines, like many others, do not generate sterilizing immunity, leaving people vulnerable to recurrent infections. Additionally, it has been discovered that the mRNA vaccines inhibit essential immunological pathways, thus impairing early interferon signaling. Within the framework of COVID-19 vaccination, this inhibition ensures an appropriate spike protein synthesis and a reduced immune activation. Evidence is provided that adding 100 % of N1-methyl-pseudouridine (m1Ψ) to the mRNA vaccine in a melanoma model stimulated cancer growth and metastasis, while non-modified mRNA vaccines induced opposite results, thus suggesting that COVID-19 mRNA vaccines could aid cancer development. Based on this compelling evidence, we suggest that future clinical trials for cancers or infectious diseases should not use mRNA vaccines with a 100 % m1Ψ modification, but rather ones with the lower percentage of m1Ψ modification to avoid immune suppression.


COVID-19 , Neoplasms , Pseudouridine , SARS-CoV-2 , Humans , COVID-19/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Neoplasms/immunology , Pseudouridine/metabolism , COVID-19 Vaccines/immunology , Animals , mRNA Vaccines , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Pneumonia, Viral/prevention & control , Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Coronavirus Infections/immunology , Coronavirus Infections/virology
13.
Funct Integr Genomics ; 24(3): 79, 2024 Apr 24.
Article En | MEDLINE | ID: mdl-38653845

Coronaviruses have been identified as pathogens of gastrointestinal and respiratory diseases in humans and various animal species. In recent years, the global spread of new coronaviruses has had profound influences for global public health and economies worldwide. As highly pathogenic zoonotic viruses, coronaviruses have become the focus of current research. Porcine Deltacoronavirus (PDCoV), an enterovirus belonging to the family of coronaviruses, has emerged on a global scale in the past decade and significantly influenced the swine industry. Moreover, PDCoV infects not only pigs but also other species, including humans, chickens and cattles, exhibiting a broad host tropism. This emphasizes the need for in-depth studies on coronaviruses to mitigate their potential threats. In this review, we provided a comprehensive summary of the current studies on PDCoV. We first reviewed the epidemiological investigations on the global prevalence and distribution of PDCoV. Then, we delved into the studies on the pathogenesis of PDCoV to understand the mechanisms how the virus impacts its hosts. Furthermore, we also presented some exploration studies on the immune evasion mechanisms of the virus to enhance the understanding of host-virus interactions. Despite current limitations in vaccine development for PDCoV, we highlighted the inhibitory effects observed with certain substances, which offers a potential direction for future research endeavors. In conclusion, this review summarized the scientific findings in epidemiology, pathogenesis, immune evasion mechanisms and vaccine development of PDCoV. The ongoing exploration of potential vaccine candidates and the insights gained from inhibitory substances have provided a solid foundation for future vaccine development to prevent and control diseases associated with PDCoV.


Coronavirus Infections , Deltacoronavirus , Immune Evasion , Swine Diseases , Viral Vaccines , Animals , Swine , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Coronavirus Infections/epidemiology , Deltacoronavirus/pathogenicity , Deltacoronavirus/immunology , Deltacoronavirus/genetics , Swine Diseases/virology , Swine Diseases/immunology , Swine Diseases/prevention & control , Swine Diseases/epidemiology , Viral Vaccines/immunology , Vaccine Development , Humans
14.
Virus Res ; 345: 199381, 2024 Jul.
Article En | MEDLINE | ID: mdl-38679392

Porcine epidemic diarrhea (PED) is a highly contagious swine intestinal disease caused by PED virus (PEDV). Vaccination is a promising strategy to prevent and control PED. Previous studies have confirmed that glycosylation could regulate the immunogenicity of viral antigens. In this study, we constructed three recombinant PEDVs which removed the glycosylation sites in RBD. Viral infection assays revealed that similar replication characteristics between the recombinant viruses and parental PEDV. Although animal challenging study demonstrated that the glycosylation sites in RBD do not affect the pathogenicity of PEDV, we found that removing the glycosylation sites on the RBD regions could promote the IgG and neutralization titer in vivo, suggesting deglycosylation in RBD could enhance the immunogenicity of PEDV. These findings demonstrated that removal of the glycosylation sites in RBD is a promising method to develop PEDV vaccines.


Antibodies, Neutralizing , Antibodies, Viral , Porcine epidemic diarrhea virus , Spike Glycoprotein, Coronavirus , Swine Diseases , Animals , Porcine epidemic diarrhea virus/immunology , Porcine epidemic diarrhea virus/genetics , Glycosylation , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/genetics , Swine , Swine Diseases/virology , Swine Diseases/immunology , Swine Diseases/prevention & control , Antibodies, Viral/immunology , Antibodies, Neutralizing/immunology , Viral Vaccines/immunology , Coronavirus Infections/prevention & control , Coronavirus Infections/veterinary , Coronavirus Infections/immunology , Coronavirus Infections/virology , Vero Cells , Chlorocebus aethiops , Immunoglobulin G/immunology , Immunoglobulin G/blood , Immunogenicity, Vaccine , Mice
15.
J Virol ; 98(5): e0195723, 2024 May 14.
Article En | MEDLINE | ID: mdl-38557247

Zoonotic coronaviruses pose a continuous threat to human health, with newly identified bat-borne viruses like swine acute diarrhea syndrome coronavirus (SADS-CoV) causing high mortality in piglets. In vitro studies indicate that SADS-CoV can infect cell lines from diverse species, including humans, highlighting its potential risk to human health. However, the lack of tools to study viral entry, along with the absence of vaccines or antiviral therapies, perpetuates this threat. To address this, we engineered an infectious molecular clone of Vesicular Stomatitis Virus (VSV), replacing its native glycoprotein (G) with SADS-CoV spike (S) and inserting a Venus reporter at the 3' leader region to generate a replication-competent rVSV-Venus-SADS S virus. Serial passages of rVSV-Venus-SADS S led to the identification of an 11-amino-acid truncation in the cytoplasmic tail of the S protein, which allowed more efficient viral propagation due to increased cell membrane anchoring of the S protein. The S protein was integrated into rVSV-Venus-SADS SΔ11 particles, susceptible to neutralization by sera from SADS-CoV S1 protein-immunized rabbits. Additionally, we found that TMPRSS2 promotes SADS-CoV spike-mediated cell entry. Furthermore, we assessed the serum-neutralizing ability of mice vaccinated with rVSV-Venus-SADS SΔ11 using a prime-boost immunization strategy, revealing effective neutralizing antibodies against SADS-CoV infection. In conclusion, we have developed a safe and practical tool for studying SADS-CoV entry and exploring the potential of a recombinant VSV-vectored SADS-CoV vaccine.IMPORTANCEZoonotic coronaviruses, like swine acute diarrhea syndrome coronavirus (SADS-CoV), pose a continual threat to human and animal health. To combat this, we engineered a safe and efficient tool by modifying the Vesicular Stomatitis Virus (VSV), creating a replication-competent rVSV-Venus-SADS S virus. Through serial passages, we optimized the virus for enhanced membrane anchoring, a key factor in viral propagation. This modified virus, rVSV-Venus-SADS SΔ11, proved susceptible to neutralization, opening avenues for potential vaccines. Additionally, our study revealed the role of TMPRSS2 in SADS-CoV entry. Mice vaccinated with rVSV-Venus-SADS SΔ11 developed potent neutralizing antibodies against SADS-CoV. In conclusion, our work presents a secure and practical tool for studying SADS-CoV entry and explores the promise of a recombinant VSV-vectored SADS-CoV vaccine.


Alphacoronavirus , Virus Internalization , Virus Replication , Animals , Humans , Mice , Rabbits , Alphacoronavirus/genetics , Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme 2/genetics , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Cell Line , Chlorocebus aethiops , Coronavirus Infections/virology , Coronavirus Infections/prevention & control , HEK293 Cells , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Serine Endopeptidases/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Swine , Vero Cells , Vesicular stomatitis Indiana virus/genetics , Vesiculovirus/genetics , Viral Vaccines/immunology , Viral Vaccines/genetics
16.
J Virol ; 98(5): e0176223, 2024 May 14.
Article En | MEDLINE | ID: mdl-38563762

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and is responsible for the largest human pandemic in 100 years. Thirty-four vaccines are currently approved for use worldwide, and approximately 67% of the world population has received a complete primary series of one, yet countries are dealing with new waves of infections, variant viruses continue to emerge, and breakthrough infections are frequent secondary to waning immunity. Here, we evaluate a measles virus (MV)-vectored vaccine expressing a stabilized prefusion SARS-CoV-2 spike (S) protein (MV-ATU3-S2PΔF2A; V591) with demonstrated immunogenicity in mouse models (see companion article [J. Brunet, Z. Choucha, M. Gransagne, H. Tabbal, M.-W. Ku et al., J Virol 98:e01693-23, 2024, https://doi.org/10.1128/jvi.01693-23]) in an established African green monkey model of disease. Animals were vaccinated with V591 or the control vaccine (an equivalent MV-vectored vaccine with an irrelevant antigen) intramuscularly using a prime/boost schedule, followed by challenge with an early pandemic isolate of SARS-CoV-2 at 56 days post-vaccination. Pre-challenge, only V591-vaccinated animals developed S-specific antibodies that had virus-neutralizing activity as well as S-specific T cells. Following the challenge, V591-vaccinated animals had lower infectious virus and viral (v) RNA loads in mucosal secretions and stopped shedding virus in these secretions earlier. vRNA loads were lower in these animals in respiratory and gastrointestinal tract tissues at necropsy. This correlated with a lower disease burden in the lungs as quantified by PET/CT at early and late time points post-challenge and by pathological analysis at necropsy.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the largest human pandemic in 100 years. Even though vaccines are currently available, countries are dealing with new waves of infections, variant viruses continue to emerge, breakthrough infections are frequent, and vaccine hesitancy persists. This study uses a safe and effective measles vaccine as a platform for vaccination against SARS-CoV-2. The candidate vaccine was used to vaccinate African green monkeys (AGMs). All vaccinated AGMs developed robust antigen-specific immune responses. After challenge, these AGMs produced less virus in mucosal secretions, for a shorter period, and had a reduced disease burden in the lungs compared to control animals. At necropsy, lower levels of viral RNA were detected in tissue samples from vaccinated animals, and the lungs of these animals lacked the histologic hallmarks of SARS-CoV-2 disease observed exclusively in the control AGMs.


COVID-19 Vaccines , COVID-19 , Measles virus , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Animals , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/genetics , Chlorocebus aethiops , SARS-CoV-2/immunology , SARS-CoV-2/genetics , COVID-19/prevention & control , COVID-19/immunology , COVID-19/virology , Measles virus/immunology , Measles virus/genetics , COVID-19 Vaccines/immunology , Humans , Antibodies, Viral/immunology , Antibodies, Viral/blood , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , Genetic Vectors , Vero Cells , Pandemics/prevention & control , Female , Betacoronavirus/immunology , Betacoronavirus/genetics , Pneumonia, Viral/prevention & control , Pneumonia, Viral/virology , Pneumonia, Viral/immunology , Coronavirus Infections/prevention & control , Coronavirus Infections/immunology , Coronavirus Infections/virology , Coronavirus Infections/veterinary , Viral Vaccines/immunology , Viral Vaccines/genetics , Viral Vaccines/administration & dosage , Disease Models, Animal
17.
J Travel Med ; 31(4)2024 Jun 03.
Article En | MEDLINE | ID: mdl-38630887

BACKGROUND: The international flight network creates multiple routes by which pathogens can quickly spread across the globe. In the early stages of infectious disease outbreaks, analyses using flight passenger data to identify countries at risk of importing the pathogen are common and can help inform disease control efforts. A challenge faced in this modelling is that the latest aviation statistics (referred to as contemporary data) are typically not immediately available. Therefore, flight patterns from a previous year are often used (referred to as historical data). We explored the suitability of historical data for predicting the spatial spread of emerging epidemics. METHODS: We analysed monthly flight passenger data from the International Air Transport Association to assess how baseline air travel patterns were affected by outbreaks of Middle East respiratory syndrome (MERS), Zika and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) over the past decade. We then used a stochastic discrete time susceptible-exposed-infected-recovered (SEIR) metapopulation model to simulate the global spread of different pathogens, comparing how epidemic dynamics differed in simulations based on historical and contemporary data. RESULTS: We observed local, short-term disruptions to air travel from South Korea and Brazil for the MERS and Zika outbreaks we studied, whereas global and longer-term flight disruptions occurred during the SARS-CoV-2 pandemic. For outbreak events that were accompanied by local, small and short-term changes in air travel, epidemic models using historical flight data gave similar projections of the timing and locations of disease spread as when using contemporary flight data. However, historical data were less reliable to model the spread of an atypical outbreak such as SARS-CoV-2, in which there were durable and extensive levels of global travel disruption. CONCLUSION: The use of historical flight data as a proxy in epidemic models is an acceptable practice, except in rare, large epidemics that lead to substantial disruptions to international travel.


Air Travel , COVID-19 , Disease Outbreaks , SARS-CoV-2 , Zika Virus Infection , Humans , Air Travel/statistics & numerical data , COVID-19/epidemiology , COVID-19/transmission , COVID-19/prevention & control , Zika Virus Infection/epidemiology , Zika Virus Infection/transmission , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/prevention & control , Communicable Diseases/epidemiology , Communicable Diseases/transmission , Travel/statistics & numerical data , Aircraft , Global Health
19.
Pol J Vet Sci ; 27(1): 143-146, 2024 Mar 20.
Article En | MEDLINE | ID: mdl-38511679

Porcine epidemic diarrhea (PED) is a disease extremely harmful to pig health. Intramuscular and Houhai acupoint injections are the main immunization routes to prevent and control PED. This study aimed to evaluate the efficacy of these two routes in pregnant sows based on serum IgG, IgA, and neutralizing antibody levels. PED virus (PEDV) immunoprophylaxis with live-attenuated and inactivated vaccines was administered. The vaccinations for the intramuscular injections elevated IgG and neutralizing antibody levels more than Houhai acupoint injections at most timepoints after immunization. However, the anti-PEDV IgA antibodies induced by vaccination with the two immunization routes did not differ significantly. In conclusion, intramuscular injections are better than Houhai acupoint injections for PEDV vaccination of pregnant sows.


Coronavirus Infections , Porcine epidemic diarrhea virus , Swine Diseases , Viral Vaccines , Pregnancy , Swine , Animals , Female , Antibodies, Viral , Coronavirus Infections/prevention & control , Coronavirus Infections/veterinary , Immunization/veterinary , Antibodies, Neutralizing , Vaccination/veterinary , Diarrhea/veterinary , Immunoglobulin G , Immunoglobulin A
20.
Nurs Open ; 11(3): e2132, 2024 Mar.
Article En | MEDLINE | ID: mdl-38488425

AIM: To systematically evaluate empirical studies investigating the influences of healthcare workers' behaviours towards infection prevention and control practices in the Coronavirus clinical space, and to appraise and synthesise these findings. DESIGN: A systematic review of the literature. METHODS: The review used a five-step framework described by Khan et al. (Journal of the Royal Society of Medicine, 2003, 96 and 118) of Framing questions for a review; Identifying relevant work; Assessing the quality of studies; Summarising the evidence; and Interpreting the findings. Searches were conducted in CINHAL, MEDLINE, PsychINFO, Scopus, and Google Scholar databases to retrieve relevant peer-reviewed literature published in English between 2019 and 2023. Covidence and Joanna Briggs Quality appraisal tools were used for critical assessment. To improve transparent reporting, this review used a Synthesis Without Meta-analysis (SWiM) in systematic review guidelines, as informed by Campbell et al. (BMJ, 2020, 368). RESULTS: Twenty studies were included in this review, identifying nine themes describing factors influencing HCWs' behaviours towards IPC practices in the coronavirus environment. The overarching influences emerged as knowledge-oriented, person-oriented, and environment-oriented. CONCLUSION: Healthcare workers' responsibilities at point-of-care involve providing direct care to patients with highly transmissible infections and working in clinical settings that may be ill-designed for IPC practices, increasing the risk of transmission. Given the lack of a definitive solution to eradicate new mutant viruses and that IPC practices are the mainstay of prevention and control of transmissible, measures to improve are imperative. The identified HCWs' domains on behaviours towards IPC are critical in strategies to mitigate risks and further set an opportunity for developing an IPC model congruent with the rapid response required for HCWs during emerging or re-merging mutant virus outbreaks. This is significant, given that HCWs' preparedness with IPC practices at point-of-care is central to patient care, the workforce and community safety.


Coronavirus Infections , Health Personnel , Humans , Coronavirus Infections/prevention & control , Coronavirus Infections/epidemiology , Disease Outbreaks
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