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1.
Pharmaceutical Technology Europe ; 34(8):19-21, 2022.
Article in English | ProQuest Central | ID: covidwho-20242828

ABSTRACT

(Note: The MIDAS database reflects vaccine doses that are dispensed with a prescription in retail or hospital settings, so the COVID-19 vaccines and other public-health-administered vaccines are not fully reflected in that data set.) Stamoran adds, "However, across the rest of the world, vial-based vaccines still make up the majority of the volume dispensed." [...]there is plenty of room for growth for this newer administration device. [...]PFS are now widely used for annual flu shots, heparin injections, and a growing list of injectable therapies across multiple disease states. According to a 2021 article authored byGuillaume Lehee, R&D Innovation Leader for BD Medical-Pharmaceutical Systems, the use of PFS to vaccinate 300 million individuals in the United States in the event of a future pandemic could save more than three million hours of healthcare practitioners' time (1). [...]today's PFS are not yet proven to be compatible with ultrafrozen temperatures as the existing glass materials and other components may not stand up to the extremely low required temperatures," explains Stamoran.

2.
Viruses ; 15(5)2023 05 11.
Article in English | MEDLINE | ID: covidwho-20243425

ABSTRACT

Antibody-dependent enhancement of infection (ADE) is clinically relevant to Dengue virus (DENV) infection and poses a major risk to the application of monoclonal antibody (mAb)-based therapeutics against related flaviviruses such as the Zika virus (ZIKV). Here, we tested a two-tier approach for selecting non-cross-reactive mAbs combined with modulating Fc glycosylation as a strategy to doubly secure the elimination of ADE while preserving Fc effector functions. To this end, we selected a ZIKV-specific mAb (ZV54) and generated three ZV54 variants using Chinese hamster ovary cells and wild-type (WT) and glycoengineered ΔXF Nicotiana benthamiana plants as production hosts (ZV54CHO, ZV54WT, and ZV54ΔXF). The three ZV54 variants shared an identical polypeptide backbone, but each exhibited a distinct Fc N-glycosylation profile. All three ZV54 variants showed similar neutralization potency against ZIKV but no ADE activity for DENV infection, validating the importance of selecting the virus/serotype-specific mAbs for avoiding ADE by related flaviviruses. For ZIKV infection, however, ZV54CHO and ZV54ΔXF showed significant ADE activity while ZV54WT completely forwent ADE, suggesting that Fc glycan modulation may yield mAb glycoforms that abrogate ADE even for homologous viruses. In contrast to the current strategies for Fc mutations that abrogate all effector functions along with ADE, our approach allowed the preservation of effector functions as all ZV54 glycovariants retained antibody-dependent cellular cytotoxicity (ADCC) against the ZIKV-infected cells. Furthermore, the ADE-free ZV54WT demonstrated in vivo efficacy in a ZIKV-infection mouse model. Collectively, our study provides further support for the hypothesis that antibody-viral surface antigen and Fc-mediated host cell interactions are both prerequisites for ADE, and that a dual-approach strategy, as shown herein, contributes to the development of highly safe and efficacious anti-ZIKV mAb therapeutics. Our findings may be impactful to other ADE-prone viruses, including SARS-CoV-2.


Subject(s)
COVID-19 , Dengue Virus , Dengue , Flavivirus , Zika Virus Infection , Zika Virus , Animals , Mice , Cricetinae , Zika Virus/genetics , CHO Cells , Dengue Virus/genetics , Cricetulus , SARS-CoV-2 , Antibodies, Viral , Antibodies, Monoclonal/therapeutic use , Cross Reactions , Antibodies, Neutralizing/therapeutic use
3.
J Biomol Struct Dyn ; : 1-19, 2023 May 26.
Article in English | MEDLINE | ID: covidwho-20241209

ABSTRACT

The new coronavirus variant (SARS-CoV-2) and Zika virus are two world-wide health pandemics. Along history, natural products-based drugs have always crucially recognized as a main source of valuable medications. Considering the SARS-CoV-2 and Zika main proteases (Mpro) as the re-production key element of the viral cycle and its main target, herein we report an intensive computer-aided virtual screening for a focused list of 39 marine lamellarins pyrrole alkaloids, against SARS-CoV-2 and Zika main proteases (Mpro) using a set of combined modern computational methodologies including molecular docking (MDock), molecule dynamic simulations (MDS) and structure-activity relationships (SARs) as well. Indeed, the molecular docking studies had revealed four promising marine alkaloids including [lamellarin H (14)/K (17)] and [lamellarin S (26)/Z (39)], according to their notable ligand-protein energy scores and relevant binding affinities with the SARS-CoV-2 and Zika (Mpro) pocket residues, respectively. Consequentially, these four chemical hits were further examined thermodynamically though investigating their MD simulations at 100 ns, where they showed prominent stability within the accommodated (Mpro) pockets. Moreover, in-deep SARs studies suggested the crucial roles of the rigid fused polycyclic ring system, particularly aromatic A- and F- rings, position of the phenolic -OH and δ-lactone functionalities as essential structural and pharmacophoric features. Finally, these four promising lamellarins alkaloids were investigated for their in-silico ADME using the SWISS ADME platform, where they displayed appropriated drug-likeness properties. Such motivating outcomes are greatly recommending further in vitro/vivo examinations regarding those lamellarins pyrrole alkaloids (LPAs).Communicated by Ramaswamy H. Sarma.

4.
Front Immunol ; 14: 1161149, 2023.
Article in English | MEDLINE | ID: covidwho-20237016

ABSTRACT

Mosquito-borne viral diseases are a group of viral illnesses that are predominantly transmitted by mosquitoes, including viruses from the Togaviridae and Flaviviridae families. In recent years, outbreaks caused by Dengue and Zika viruses from the Flaviviridae family, and Chikungunya virus from the Togaviridae family, have raised significant concerns for public health. However, there are currently no safe and effective vaccines available for these viruses, except for CYD-TDV, which has been licensed for Dengue virus. Efforts to control the transmission of COVID-19, such as home quarantine and travel restrictions, have somewhat limited the spread of mosquito-borne viral diseases. Several vaccine platforms, including inactivated vaccines, viral-vector vaccines, live attenuated vaccines, protein vaccines, and nucleic acid vaccines, are being developed to combat these viruses. This review analyzes the various vaccine platforms against Dengue, Zika, and Chikungunya viruses and provides valuable insights for responding to potential outbreaks.


Subject(s)
COVID-19 , Chikungunya virus , Culicidae , Dengue , Viral Vaccines , Zika Virus Infection , Zika Virus , Animals , Humans , Mosquito Vectors , Zika Virus Infection/epidemiology , Zika Virus Infection/prevention & control , Vaccines, Attenuated , Dengue/epidemiology , Dengue/prevention & control , Vaccine Development
5.
Clinical Immunology: Principles and Practice, Sixth Edition ; : 399-411, 2022.
Article in English | Scopus | ID: covidwho-2322541

ABSTRACT

Pandemic infectious diseases are caused by pathogens that have adapted well to growth and reproduction within the human host and that through unique environmental, socioeconomic, and cultural circumstances are able to rapidly spread across national boundaries and even globally. Although uncommon and caused by relatively few pathogens, the extraordinary human, economic, and societal losses caused by pandemic diseases as exemplified by coronavirus disease 2019 (COVID-19) make pandemic diseases of unique importance to clinicians, immunologists, and many other scientists and healthcare professionals. The pathogenesis of pandemic diseases is complex and unique to each pathogen, but common to all is widespread immunologic naïveté within the host population. In this chapter, we consider the pathogens of greatest concern for their pandemic potential. Most of these organisms are viruses, including betacoronaviruses, alpha influenza virus, Ebola virus, and the flaviviruses, but numerous bacteria are also emerging with pandemic disease potential. For each organism, we consider the factors, especially immunologic, that lead to pandemic spread and prospects for effective therapy and prevention. © 2023 Elsevier Ltd. All rights reserved.

6.
VirusDisease ; 34(1):98, 2023.
Article in English | EMBASE | ID: covidwho-2320585

ABSTRACT

The COVID-19 pandemic has severely affected public health system and surveillance of other communicable diseases across the globe. The lockdown, travel constraints and COVID phobia turned down the number of people with illness visiting to the clinics or hospitals. Besides this, the heavy workload of SARS-CoV-2 diagnosis has led to the reduction in differential diagnosis of other diseases. Consequently, it added to the underlying burden of many diseases which remained under-diagnosed. Amidst the pandemic, the rise of emerging and re-emerging infectious diseases was observed worldwide and reported to the World Health Organization i.e., Crimean Congo Hemorrhagic Fever (2022, Iraq;2021 India), Nipah virus (2021, India), Zika virus (2021, India), and H5N1 influenza (2021, India), Monkeypox (2022, multicountry outbreak), Ebola virus disease (2022, DRC, Uganda;2021, DRC, Guinea;2020, DRC), Marburg (2022, Ghana;2021, Guinea), Yellow fever (2022, Uganda, Kenya, West and Central Africa;2021, Ghana, Venezuela, Nigeria;2020, Senegal, Guinea, Nigeria, Gabon;2020, Ethiopia, Sudan, Uganda), Dengue (2022, Nepal, Pakistan, Sao Tome, Temor-Leste;2021, Pakistan), Middle east respiratory syndrome coronavirus (2022, Oman, Qatar;2021, Saudi Arabia, UAE;2020, Saudi Arabia, UAE), Rift valley fever (2021, Kenya;2020, Mauritania), wild poliovirus type 1 (2022, Mozambique), Lassa fever (2022, Guinea, Togo, Nigeria;2020, Nigeria), Avian Influenza (H3N8) (2022, China), Avian Influenza (H5N1) (2022, USA), H10N3 influenza (2021, China), Hepatitis E virus (2022, Sudan), Measles (2022, Malawi, Afghanistan;2020, Burundi, Mexico), Mayaro virus disease (2020, French Guiana), Oropouche virus disease (2020, French Guiana). All these diseases were associated with high morbidity and burdened the public health system during the COVID-19 pandemic. During this critical public health menace, majority of the laboratory workforce was mobilized to the SARS-CoV-2 diagnosis. This has limited the surveillance efforts that likely led to under diagnosis and under-detection of many infectious pathogens. Lockdowns and travel limitations also put a hold on human and animal surveillance studies to assess the prevalence of these zoonotic viruses. In addition, lack of supplies and laboratory personnel and an overburdened workforce negatively impacted differential diagnosis of the diseases. This is especially critical given the common symptoms between COVID-19 and other pathogens causing respiratory illnesses. Additionally, the vaccination programs against various vaccine preventable diseases were also hampered which might have added to the disease burden. Despite these challenges, the world is better prepared to detect and respond to emerging/re-emerging pathogens. India now has more than 3000 COVID-19 diagnostic laboratories and an enhanced hospital infrastructure. In addition, mobile BSL-3 facilities are being validated for onsite sampling and testing in remote areas during outbreak situations and surveillance activities. This will undoubtedly be valuable as the COVID-19 pandemic evolves as well as during future outbreaks and epidemics. In conclusion, an increase in the emergence and re-emergence of viruses demonstrates that other infectious diseases have been neglected during the COVID-19 pandemic. Lessons learned from the infrastructure strengthening, collaborations with multiple stakeholders, increased laboratory and manufacturing capacity, large-scale COVID-19 surveillance, extensive network for laboratory diagnosis, and intervention strategies can be implemented to provide quick, concerted responses against the future threats associated with other zoonotic pathogens.

7.
Journal of Chemistry ; 2023, 2023.
Article in English | ProQuest Central | ID: covidwho-2320526

ABSTRACT

The main protease (Mpro) of SARS-CoV-2 is a well-established drug target for rational drug design of COVID-19 inhibitors. To address the serious challenge of COVID-19, we have performed biochemical inhibition screens with recombinantly expressed SARS-CoV-2 main protease (Mpro). A fluorescent assay was used to identify the flavonoid isoquercitrin as an Mpro inhibitor. Both isoquercitrin encapsulated in γ-cyclodextrin (inclusion complex formulations) and alone inhibited SARS-CoV-2 Mpro. For isoquercitrin, a Ki value of 32 μM (IC50 = 63 μM) was obtained. Isoquercitrin γ-cyclodextrin inclusion complex formulations additionally inhibited Zika virus NS2B-NS3pro leading to an IC50 value of 98 μM. Formulations containing the other flavonoid compounds diosmetin-7-O-glucoside, hesperetin-7-O-glucoside, and naringenin-7-O-glucoside did not inhibit SARS-CoV-2 Mpro. Steady-state kinetics indicate that the inhibition mechanism of Mpro by isoquercitrin is potentially competitive. Molecular modeling studies carried out with MM/PBSA confirm the likely modes of isoquercitrin binding to both proteases. These modeling results can be used in the development of structural analogs of isoquercitrin with better inhibitory profiles and potential candidates for anti-coronavirus drugs. Since the targeted proteases are essential for viral activity, the delivery isoquercitrin-cyclodextrin inclusion complex formulations could be of great interest for the development of future antiviral drugs to target intracellular virus proteins or other components.

8.
Topics in Antiviral Medicine ; 31(2):215, 2023.
Article in English | EMBASE | ID: covidwho-2318132

ABSTRACT

Background: Different viruses employ similar pathways for replication, revealing key intracellular hotspots to target with host-directed therapies and achieve a broad-spectrum antiviral activity. Plitidepsin is a clinically approved antitumoral agent that blocks the elongation factor eEF1A required for protein translation. This drug counteracts SARS-CoV-2 replication and shows a favorable safety profile in COVID-19 patients. Yet, the precise antiviral mechanism of action of plitidepsin remains unknown. Method(s): Here we used a deep quantitative proteomic analysis to measure the impact of plitidepsin on the proteome of SARS-CoV-2-infected Vero E6 cells. This was complemented with transmission electron microscopy assays, which unraveled the subcellular and morphological changes associated to plitidepsin treatment. In addition, we performed functional in vitro assays to dissect the antiviral activity of plitidepsin against SARS-CoV-2 and other viruses. Result(s): We found that this drug inhibited the synthesis of all SARS-CoV-2 proteins in a dose-dependent manner. These included the R1AB polyproteins, which facilitate the synthesis of non-structural proteins involved in the formation of double membrane vesicles (DMV) required for viral replication. Plitidepsin reduced DMV formation and the morphogenesis of new viruses, having a greater impact on viral than on host proteins. Less than 14% of the cellular proteome was significantly affected by plitidepsin, inducing the up-regulation of key molecules associated with protein biosynthesis, such as the translation initiation factors eIF4A2 and eIF2S3. Therefore, plitidepsin induced a compensatory state that rescued protein translation. This proteostatic response explains how cells preserve the cellular proteome after treatment with a translation inhibitor such as plitidepsin. In addition, it suggests that plitidepsin could inhibit other RNA-dependent and non-integrated DNA viruses, as we confirmed in vitro using Zika virus, Hepatitis C virus replicon and Herpes simplex virus. However, the compensatory proteostasis induced by plitidespin also explains why this drug failed to inhibit the replication of integrated DNA proviruses such as HIV-1. Conclusion(s): Unraveling the mechanism of action of host-directed therapies like plitidepsin is imperative to define the indications and antiviral profile of these compounds. This knowledge will be key to develop broad-spectrum treatments and have them ready to deploy when future pandemic viruses break through.

9.
Drugs of the Future ; 48(1):63-67, 2023.
Article in English | EMBASE | ID: covidwho-2317670

ABSTRACT

IDWeek is the joint annual meeting of the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS) and the Society of Infectious Diseases Pharmacists (SIDP). For the first time since the COVID-19 public health emergency began, IDWeek 2022 returned to in-person attendance. It was held in Washington, D.C., and the meeting comprised 5 days of live sessions and on-demand content that included posters and oral presentations.Copyright © 2023 Clarivate.

10.
Methods in Molecular Biology ; 2621:v, 2023.
Article in English | EMBASE | ID: covidwho-2317522
11.
Journal of Investigative Medicine ; 71(1):183, 2023.
Article in English | EMBASE | ID: covidwho-2312150

ABSTRACT

Case Report: This is a 50-year-old man that presented to the ED complaining of generalized weakness and acute loss of ability to ambulate which has been progressing for a month. Patient began having left arm and leg weakness, which started in his fingertips of his left upper extremity and soon moved proximally to upper left arm. Symptoms then progressed to right upper and lower arms. Symptoms further continued to progress making the patient bedridden. On presentation, CT head showed a C1/C2 subluxation possibly chronic without significant focal soft tissue swelling. CT cervical spine showed C1-C2 subluxation, possibly chronic. MRI of brain was unremarkable pre and postcontrast without focal findings or abnormal enhancement and showed redemonstration of the C1-C2 subluxation as described on CT scan. MRI of cervical spine showed at the level of C1 there is spinal canal stenosis. However, there is no direct pressure upon the cord/medulla. Upon evaluation, patient had significant motor weakness and required maximal assistance for movement. Patient was moreover noted to have flaccidity of muscles associated with weakness with no bulbar weakness. Patient had no difficulty in breathing or with speech. A lumbar tap was performed which showed elevated protein, WBC, and glucose. Upon further investigation, patient stated that he received his (3rd dose) of the Moderna Vaccine for Covid-19 about a month before the onset of symptoms and felt fine. Two weeks later, he began experiencing subjective fevers, diarrhea, abdominal pain, and fatigue that lasted for a week and then self-resolved. Approximately another two weeks later is when patient began noticing his neurological symptoms. Possible Guillain-Barre Syndrome post Campylobacter Jejuni (C. Jejuni) infection vs. post Covid-19 vaccine induced GBS was suspected at this point and patient was started on Intravenous Immunoglobulin (IVIG). Stool cultures were collected for C.Jejuni which came back negative. Gastrointestinal Pathogen Panel PCR Feces also came back negative. Patient was discharged to a rehab center and planned to receive another round of IVIG for 5 days. Conclusion(s): Guillain Barre Syndrome (GBS) is a rare immune-mediated neurological disorder affecting peripheral nerves and nerve roots, that presents as acute sensorimotor neuropathy starting with distal paresthesia that progresses to weakness of legs and arms, noteably, flaccid paralysis. GBS has several triggers namely infections such as C. jejuni, cytomegalovirus, M. pneumoniae, Epstien-Barr virus and Zika virus. There has also been several case reports and studies that have shown increased incidence of GBS vaccines such as influenza vaccine. Furthermore, there has been several studies that have linked GBS to COVID-19 vaccine. With COVID-19 cases continuing to persist, and increasing advocacy for vaccination against the disease, GBS should be considered as very rare but possible side effect of the vaccine.

12.
Birth Defects Res ; 115(5): 572-577, 2023 03 15.
Article in English | MEDLINE | ID: covidwho-2314025

ABSTRACT

BACKGROUND: The United States Virgin Islands (USVI) Department of Health (DOH) conducted a second Zika health brigade (ZHB) in 2021 to provide recommended Zika-related pediatric health screenings, including vision, hearing, neurologic, and developmental screenings, for children in the USVI. This was replicated after the success of the first ZHB in 2018, which provided recommended Zika-related pediatric health screenings to 88 infants and children exposed to Zika virus (ZIKV) during pregnancy. METHODS: Ten specialty pediatric care providers were recruited and traveled to the USVI to conduct the screenings. USVI DOH scheduled appointments for children included in CDC's U.S. Zika Pregnancy and Infant Registry (USZPIR). During the ZHB, participants were examined by pediatric ophthalmologists, pediatric audiologists, and pediatric neurologists. We report the percentage of participants who were referred for additional follow-up care or given follow-up recommendations in the 2021 ZHB and compare these referrals and recommendations to those given in the 2018 ZHB. RESULTS: Thirty-three children born to mothers with laboratory evidence of ZIKV infection during pregnancy completed screenings at the 2021 ZHB, of which 15 (45%) children were referred for additional follow-up care. Ophthalmological screenings resulted in the highest number of new referrals for a specialty provider among ZHB participants, with 6 (18%) children receiving referrals for that specialty. Speech therapy was the most common therapy referral, with 10 (30%) children referred, of which 9 (90%) were among those who attended the 2018 ZHB. CONCLUSIONS: Thirty-three children in a jurisdiction with reduced access to healthcare specialists received recommended Zika-related pediatric health screenings at the ZHB. New and continuing medical and developmental concerns were identified and appropriate referrals for follow-up care and services were provided. The ZHB model was successful in creating connections to health services not previously received by the participants.


Subject(s)
Pregnancy Complications, Infectious , Zika Virus Infection , Zika Virus , Pregnancy , Infant , Female , Humans , Child , United States Virgin Islands , Parturition
13.
Viral Immunol ; 35(9): 586-596, 2022 11.
Article in English | MEDLINE | ID: covidwho-2313628

ABSTRACT

Infection caused by the Zika virus (ZIKV) can lead to serious neurological complications such as microcephaly in neonates. At present, no approved ZIKV vaccine is available, but few vaccine candidates are undergoing clinical trial. One major challenge faced is antibody-dependent enhancement (ADE) reaction that may provoke severe outcome in subsequent infection by ZIKV or other flaviviruses. Thus, more efforts should be dedicated to understanding ADE in designing a safe and effective vaccine to minimize the consequence of the potentially fatal infection's complications and to tackle potential ZIKV reemergence. This review discusses different types of ZIKV vaccine candidates that are currently underway in various stages of preclinical and clinical evaluations.


Subject(s)
Viral Vaccines , Zika Virus Infection , Zika Virus , Infant, Newborn , Humans , Antibody-Dependent Enhancement , Antibodies, Viral
14.
Journal of Pacific Rim Psychology ; 15, 2021.
Article in English | ProQuest Central | ID: covidwho-2292220

ABSTRACT

Many conspiracy theories appeared along with the Zika outbreak. While the virus is still circulating, motives underlying Zika conspiracy beliefs remain underexplored. National narcissism has been shown to be a robust social motive predicting conspiracy beliefs about other public health crises. This relationship has been interpreted as conspiracy beliefs protecting one's idealistic national image from the crisis by externally attributing any potential threatening factors. We seek to provide an additional account by proposing that such external projection of grievances is rooted in the ethnocentric tendency to frame one's nation's suffering as central to the crisis. We argue that this inflated perception of victimhood, which we operationalized through exclusive victimhood, legitimizes national narcissists' expression of their (conspiracy) view of the crisis, hence managing their identity. Based on a representative sample of the French population (N = 1,104), results confirmed that national narcissism was related to Zika conspiracy beliefs, and that this relationship was mediated by the belief that French people suffered uniquely and more than others from the Zika outbreak. These results held even when controlling for potential confounding variables. We discuss the possible functions of exclusive victimhood in times of global threats, and the defensive role played by conspiracy beliefs.

15.
Journal of Pacific Rim Psychology ; 15, 2021.
Article in English | ProQuest Central | ID: covidwho-2306172

ABSTRACT

Understanding why people believe conspiracy theories related to disease outbreaks and the consequences of such beliefs is critical for combating both the COVID-19 pandemic and its corresponding "infodemic.” In the introduction to this special issue on conspiracy theories about infectious diseases, the authors first provide a brief overview of the narratives of conspiracy theories related to COVID-19, followed by a review of extant theoretical frameworks regarding the psychology of conspiracy beliefs. Specifically, they discuss how epistemic, existential, and social needs contribute to the holding of conspiracy beliefs. Then, the authors summarize the major findings from the nine empirical articles featured in this issue, particularly how they shed light on the antecedents and consequences of disease-related conspiracy beliefs. They conclude by discussing future directions for the study of disease-related conspiracy beliefs.

16.
Cell Rep Med ; 4(5): 101024, 2023 05 16.
Article in English | MEDLINE | ID: covidwho-2295352

ABSTRACT

RNA viruses continue to remain a threat for potential pandemics due to their rapid evolution. Potentiating host antiviral pathways to prevent or limit viral infections is a promising strategy. Thus, by testing a library of innate immune agonists targeting pathogen recognition receptors, we observe that Toll-like receptor 3 (TLR3), stimulator of interferon genes (STING), TLR8, and Dectin-1 ligands inhibit arboviruses, Chikungunya virus (CHIKV), West Nile virus, and Zika virus to varying degrees. STING agonists (cAIMP, diABZI, and 2',3'-cGAMP) and Dectin-1 agonist scleroglucan demonstrate the most potent, broad-spectrum antiviral function. Furthermore, STING agonists inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enterovirus-D68 (EV-D68) infection in cardiomyocytes. Transcriptome analysis reveals that cAIMP treatment rescue cells from CHIKV-induced dysregulation of cell repair, immune, and metabolic pathways. In addition, cAIMP provides protection against CHIKV in a chronic CHIKV-arthritis mouse model. Our study describes innate immune signaling circuits crucial for RNA virus replication and identifies broad-spectrum antivirals effective against multiple families of pandemic potential RNA viruses.


Subject(s)
COVID-19 , Chikungunya virus , RNA Viruses , Zika Virus Infection , Zika Virus , Animals , Mice , SARS-CoV-2 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Chikungunya virus/physiology , Immunity, Innate
17.
Vaccines (Basel) ; 11(4)2023 Apr 10.
Article in English | MEDLINE | ID: covidwho-2301599

ABSTRACT

The severe consequences of the Zika virus (ZIKV) infections resulting in congenital Zika syndrome in infants and the autoimmune Guillain-Barre syndrome in adults warrant the development of safe and efficacious vaccines and therapeutics. Currently, there are no approved treatment options for ZIKV infection. Herein, we describe the development of a bacterial ferritin-based nanoparticle vaccine candidate for ZIKV. The viral envelope (E) protein domain III (DIII) was fused in-frame at the amino-terminus of ferritin. The resulting nanoparticle displaying the DIII was examined for its ability to induce immune responses and protect vaccinated animals upon lethal virus challenge. Our results show that immunization of mice with a single dose of the nanoparticle vaccine candidate (zDIII-F) resulted in the robust induction of neutralizing antibody responses that protected the animals from the lethal ZIKV challenge. The antibodies neutralized infectivity of other ZIKV lineages indicating that the zDIII-F can confer heterologous protection. The vaccine candidate also induced a significantly higher frequency of interferon (IFN)-γ positive CD4 T cells and CD8 T cells suggesting that both humoral and cell-mediated immune responses were induced by the vaccine candidate. Although our studies showed that a soluble DIII vaccine candidate could also induce humoral and cell-mediated immunity and protect from lethal ZIKV challenge, the immune responses and protection conferred by the nanoparticle vaccine candidate were superior. Further, passive transfer of neutralizing antibodies from the vaccinated animals to naïve animals protected against lethal ZIKV challenge. Since previous studies have shown that antibodies directed at the DIII region of the E protein do not to induce antibody-dependent enhancement (ADE) of ZIKV or other related flavivirus infections, our studies support the use of the zDIII-F nanoparticle vaccine candidate for safe and enhanced immunological responses against ZIKV.

18.
The Lancet Global Health ; 11(3):e306-e307, 2023.
Article in English | EMBASE | ID: covidwho-2270519
19.
One Health Bulletin ; 2(16), 2022.
Article in English | CAB Abstracts | ID: covidwho-2288530

ABSTRACT

Vaccination is effective in preventing the increase of disease, especially emerging infectious diseases (EIDs), and it is particularly important for people in close contact with infected sources and susceptible populations who are at increased risk of getting infectious diseases due to behavior, occupation or health. Despite targeted vaccination guidelines, inadequate vaccination of the key populations fails to receive widespread attention, resulting in a high-risk transition of disease from key populations to general populations. Strengthening the vaccination of the susceptible groups can effectively block the spread of pathogens to general populations, and reduce the consumption of medical resources in universal vaccination, which has significant economic value. In this review, we describe the prevalence of EIDs, analyze the experience and lessons of infectious disease vaccination in key populations through several cases, and further explore the causes for the decline in vaccination rates of key populations. According to the trends of EIDs, a plan to strengthen the vaccination of key populations is proposed to effectively prevent the transition of EIDs from key populations to general populations.

20.
Food Research ; 7(1):76-92, 2023.
Article in English | EMBASE | ID: covidwho-2282815

ABSTRACT

Iron is a mineral that plays an important role, especially to prevent anaemia through the production of red blood cells. Iron also plays a role in physiological processes, such as the activation of enzymes and hormones, as well as increasing the immune system in warding off various viral infections. Therefore, iron bioavailability needs to be considered to take the greatest benefit of iron. This review discussed the factors that can affect the bioavailability of iron, various technologies to increase the bioavailability, and its potential in enhancing the immune system. Iron bioavailability can be increased by fortification, fermentation, the addition of vitamin C, and iron encapsulation. Under conditions of adequate iron intake, iron plays an important role in enhancing the immune system through controlling lymphocytes and T cell proliferation. However, excess iron consumption can be at risk of weakening the host's immune response to viruses. Therefore, the appropriate level of iron intake must be maintained accurately to be used optimally and has the potential to ward off viral infections, including the Sars-CoV-2 virus as the cause of COVID-19.Copyright © 2023, Rynnye Lyan Resources. All rights reserved.

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