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1.
PLoS Pathog ; 18(2): e1010282, 2022 02.
Article in English | MEDLINE | ID: covidwho-1753213

ABSTRACT

Immunization with radiation-attenuated sporozoites (RAS) can confer sterilizing protection against malaria, although the mechanisms behind this protection are incompletely understood. We performed a systems biology analysis of samples from the Immunization by Mosquito with Radiation Attenuated Sporozoites (IMRAS) trial, which comprised P. falciparum RAS-immunized (PfRAS), malaria-naive participants whose protection from malaria infection was subsequently assessed by controlled human malaria infection (CHMI). Blood samples collected after initial PfRAS immunization were analyzed to compare immune responses between protected and non-protected volunteers leveraging integrative analysis of whole blood RNA-seq, high parameter flow cytometry, and single cell CITEseq of PBMCs. This analysis revealed differences in early innate immune responses indicating divergent paths associated with protection. In particular, elevated levels of inflammatory responses early after the initial immunization were detrimental for the development of protective adaptive immunity. Specifically, non-classical monocytes and early type I interferon responses induced within 1 day of PfRAS vaccination correlated with impaired immunity. Non-protected individuals also showed an increase in Th2 polarized T cell responses whereas we observed a trend towards increased Th1 and T-bet+ CD8 T cell responses in protected individuals. Temporal differences in genes associated with natural killer cells suggest an important role in immune regulation by these cells. These findings give insight into the immune responses that confer protection against malaria and may guide further malaria vaccine development. Trial registration: ClinicalTrials.gov NCT01994525.


Subject(s)
Immunity , Inflammation , Malaria Vaccines/immunology , Malaria, Falciparum/immunology , Plasmodium falciparum/immunology , Sporozoites/immunology , Adult , Animals , Anopheles/parasitology , Female , Humans , Immunization/methods , Insect Bites and Stings/immunology , Malaria, Falciparum/parasitology , Male , Mosquito Vectors/parasitology , T-Lymphocytes/immunology , Vaccination/methods , Vaccines, Attenuated/immunology
2.
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
3.
J Clin Immunol ; 42(2): 240-252, 2022 02.
Article in English | MEDLINE | ID: covidwho-1520401

ABSTRACT

Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and/or a defective antibody response to T-dependent and T-independent antigens. CVID response to immunization depends on the antigen type, the vaccine mechanism, and the specific patient immune defect. In CVID patients, humoral and cellular responses to the currently used COVID-19 vaccines remain unexplored. Eighteen CVID subjects receiving 2-dose anti-SARS-CoV-2 vaccines were prospectively studied. S1-antibodies and S1-specific IFN-γ T cell response were determined by ELISA and FluoroSpot, respectively. The immune response was measured before the administration and after each dose of the vaccine, and it was compared to the response of 50 healthy controls (HC). The development of humoral and cellular responses was slower in CVID patients compared with HC. After completing vaccination, 83% of CVID patients had S1-specific antibodies and 83% had S1-specific T cells compared with 100% and 98% of HC (p = 0.014 and p = 0.062, respectively), but neutralizing antibodies were detected only in 50% of the patients. The strength of both humoral and cellular responses was significantly lower in CVID compared with HC, after the first and second doses of the vaccine. Absent or discordant humoral and cellular responses were associated with previous history of autoimmunity and/or lymphoproliferation. Among the three patients lacking humoral response, two had received recent therapy with anti-B cell antibodies. Further studies are needed to understand if the response to COVID-19 vaccination in CVID patients is protective enough. The 2-dose vaccine schedule and possibly a third dose might be especially necessary to achieve full immune response in these patients.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , Common Variable Immunodeficiency/immunology , Immunogenicity, Vaccine/immunology , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Female , Humans , Immunity, Cellular/immunology , Immunity, Humoral/immunology , Immunization/methods , Immunoglobulin G/immunology , Male , Middle Aged , Prospective Studies , Spike Glycoprotein, Coronavirus , T-Lymphocytes/immunology , Vaccination/methods , Young Adult
4.
Viruses ; 13(11)2021 11 02.
Article in English | MEDLINE | ID: covidwho-1502527

ABSTRACT

The COVID-19 pandemic has currently created an unprecedented threat to human society and global health. A rapid mass vaccination to create herd immunity against SARS-CoV-2 is a crucial measure to ease the spread of this disease. Here, we investigated the immunogenicity of a SARS-CoV-2 subunit vaccine candidate, a SARS-CoV-2 spike glycoprotein encapsulated in N,N,N-trimethyl chitosan particles or S-TMC NPs. Upon intraperitoneal immunization, S-TMC NP-immunized mice elicited a stronger systemic antibody response, with neutralizing capacity against SARS-CoV-2, than mice receiving the soluble form of S-glycoprotein. S-TMC NPs were able to stimulate the circulating IgG and IgA as found in SARS-CoV-2-infected patients. In addition, spike-specific T cell responses were drastically activated in S-TMC NP-immunized mice. Surprisingly, administration of S-TMC NPs via the intraperitoneal route also stimulated SARS-CoV-2-specific immune responses in the respiratory tract, which were demonstrated by the presence of high levels of SARS-CoV-2-specific IgG and IgA in the lung homogenates and bronchoalveolar lavages of the immunized mice. We found that peritoneal immunization with spike nanospheres stimulates both systemic and respiratory mucosal immunity.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , COVID-19/virology , Immunity , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Subunit/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antibody Formation , COVID-19/prevention & control , Female , Humans , Immunity, Mucosal , Immunization/methods , Immunogenicity, Vaccine , Mice , Mice, Inbred BALB C , Nanoparticles/therapeutic use , Recombinant Proteins/immunology , Respiratory System/immunology , T-Lymphocytes/immunology , Vaccination , Vaccines, Subunit/administration & dosage
5.
Mol Ther ; 30(1): 311-326, 2022 01 05.
Article in English | MEDLINE | ID: covidwho-1450246

ABSTRACT

The COVID-19 pandemic caused by SARS-CoV-2 has made the development of safe and effective vaccines a critical priority. To date, four vaccines have been approved by European and American authorities for preventing COVID-19, but the development of additional vaccine platforms with improved supply and logistics profiles remains a pressing need. Here we report the preclinical evaluation of a novel COVID-19 vaccine candidate based on the electroporation of engineered, synthetic cDNA encoding a viral antigen in the skeletal muscle. We constructed a set of prototype DNA vaccines expressing various forms of the SARS-CoV-2 spike (S) protein and assessed their immunogenicity in animal models. Among them, COVID-eVax-a DNA plasmid encoding a secreted monomeric form of SARS-CoV-2 S protein receptor-binding domain (RBD)-induced the most potent anti-SARS-CoV-2 neutralizing antibody responses (including against the current most common variants of concern) and a robust T cell response. Upon challenge with SARS-CoV-2, immunized K18-hACE2 transgenic mice showed reduced weight loss, improved pulmonary function, and lower viral replication in the lungs and brain. COVID-eVax conferred significant protection to ferrets upon SARS-CoV-2 challenge. In summary, this study identifies COVID-eVax as an ideal COVID-19 vaccine candidate suitable for clinical development. Accordingly, a combined phase I-II trial has recently started.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Immunization/methods , Models, Animal , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/immunology , Vaccines, DNA/administration & dosage , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/genetics , COVID-19/virology , Female , Ferrets , Humans , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Transgenic , Protein Domains , Rats, Sprague-Dawley
7.
Cell Rep ; 37(2): 109823, 2021 10 12.
Article in English | MEDLINE | ID: covidwho-1433047

ABSTRACT

Although both infections and vaccines induce memory B cell (MBC) populations that participate in secondary immune responses, the MBCs generated in each case can differ. Here, we compare SARS-CoV-2 spike receptor binding domain (S1-RBD)-specific primary MBCs that form in response to infection or a single mRNA vaccination. Both primary MBC populations have similar frequencies in the blood and respond to a second S1-RBD exposure by rapidly producing plasmablasts with an abundant immunoglobulin (Ig)A+ subset and secondary MBCs that are mostly IgG+ and cross-react with the B.1.351 variant. However, infection-induced primary MBCs have better antigen-binding capacity and generate more plasmablasts and secondary MBCs of the classical and atypical subsets than do vaccine-induced primary MBCs. Our results suggest that infection-induced primary MBCs have undergone more affinity maturation than vaccine-induced primary MBCs and produce more robust secondary responses.


Subject(s)
COVID-19 Vaccines/immunology , Plasma Cells/immunology , SARS-CoV-2/immunology , Adult , Animals , Antibodies, Viral/immunology , B-Lymphocyte Subsets/immunology , B-Lymphocytes/immunology , COVID-19/immunology , COVID-19/metabolism , Cross Reactions/immunology , Female , HEK293 Cells , Humans , Immunization/methods , Immunologic Memory , Male , Mice , Mice, Inbred C57BL , Middle Aged , RNA, Messenger/immunology , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Vaccination/methods , Vaccines/immunology
8.
Commun Biol ; 4(1): 597, 2021 05 19.
Article in English | MEDLINE | ID: covidwho-1236095

ABSTRACT

The COVID-19 pandemic continues to wreak havoc as worldwide SARS-CoV-2 infection, hospitalization, and death rates climb unabated. Effective vaccines remain the most promising approach to counter SARS-CoV-2. Yet, while promising results are emerging from COVID-19 vaccine trials, the need for multiple doses and the challenges associated with the widespread distribution and administration of vaccines remain concerns. Here, we engineered the coat protein of the MS2 bacteriophage and generated nanoparticles displaying multiple copies of the SARS-CoV-2 spike (S) protein. The use of these nanoparticles as vaccines generated high neutralizing antibody titers and protected Syrian hamsters from a challenge with SARS-CoV-2 after a single immunization with no infectious virus detected in the lungs. This nanoparticle-based vaccine platform thus provides protection after a single immunization and may be broadly applicable for protecting against SARS-CoV-2 and future pathogens with pandemic potential.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/immunology , COVID-19/prevention & control , Pandemics , SARS-CoV-2 , Animals , Antibodies, Neutralizing/biosynthesis , Antibodies, Viral/biosynthesis , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , Drug Delivery Systems , Female , Humans , Immunization/methods , Levivirus/genetics , Levivirus/immunology , Mesocricetus , Microscopy, Electron, Transmission , Models, Animal , Nanoparticles/administration & dosage , Nanoparticles/ultrastructure , Nanotechnology , Pandemics/prevention & control , Protein Engineering , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/administration & dosage , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Combined/administration & dosage , Vaccines, Combined/genetics , Vaccines, Combined/immunology , Vaccines, Virus-Like Particle/administration & dosage , Vaccines, Virus-Like Particle/genetics , Vaccines, Virus-Like Particle/immunology
9.
Life Sci ; 278: 119580, 2021 Aug 01.
Article in English | MEDLINE | ID: covidwho-1225325

ABSTRACT

COVID-19 pandemic is still a major risk to human civilization. Besides the global immunization policy, more than five lac new cases are documented everyday. Some countries newly implement partial/complete nationwid lockdown to mitigate recurrent community spreading. To avoid the new modified stain of SARS-CoV-2 spreading, some countries imposed any restriction on the movement of the citizens within or outside the country. Effective economical point of care diagnostic and therapeutic strategy is vigorously required to mitigate viral spread. Besides struggling with repurposed medicines, new engineered materials with multiple unique efficacies and specific antiviral potency against SARS-CoV-2 infection may be fruitful to save more lives. Nanotechnology-based engineering strategy sophisticated medicine with specific, effective and nonhazardous delivery mechanism for available repurposed antivirals as well as remedial for associated diseases due to malfeasance in immuno-system e.g. hypercytokinaemia, acute respiratory distress syndrome. This review will talk about gloomy but critical areas for nanoscientists to intervene and will showcase about the different laboratory diagnostic, prognostic strategies and their mode of actions. In addition, we speak about SARS-CoV-2 pathophysiology, pathogenicity and host specific interation with special emphasis on altered immuno-system and also perceptualized, copious ways to design prophylactic nanomedicines and next-generation vaccines based on recent findings.


Subject(s)
COVID-19/therapy , Theranostic Nanomedicine/methods , Animals , Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , COVID-19/diagnosis , COVID-19/immunology , COVID-19/pathology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/therapeutic use , Drug Delivery Systems/methods , Humans , Immunization/methods , Nanotechnology/methods , Precision Medicine/methods , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification
10.
Sci Rep ; 11(1): 9825, 2021 05 10.
Article in English | MEDLINE | ID: covidwho-1223113

ABSTRACT

In the current global emergency due to SARS-CoV-2 outbreak, passive immunotherapy emerges as a promising treatment for COVID-19. Among animal-derived products, equine formulations are still the cornerstone therapy for treating envenomations due to animal bites and stings. Therefore, drawing upon decades of experience in manufacturing snake antivenom, we developed and preclinically evaluated two anti-SARS-CoV-2 polyclonal equine formulations as potential alternative therapy for COVID-19. We immunized two groups of horses with either S1 (anti-S1) or a mixture of S1, N, and SEM mosaic (anti-Mix) viral recombinant proteins. Horses reached a maximum anti-viral antibody level at 7 weeks following priming, and showed no major adverse acute or chronic clinical alterations. Two whole-IgG formulations were prepared via hyperimmune plasma precipitation with caprylic acid and then formulated for parenteral use. Both preparations had similar physicochemical and microbiological quality and showed ELISA immunoreactivity towards S1 protein and the receptor binding domain (RBD). The anti-Mix formulation also presented immunoreactivity against N protein. Due to high anti-S1 and anti-RBD antibody content, final products exhibited high in vitro neutralizing capacity of SARS-CoV-2 infection, 80 times higher than a pool of human convalescent plasma. Pre-clinical quality profiles were similar among both products, but clinical efficacy and safety must be tested in clinical trials. The technological strategy we describe here can be adapted by other producers, particularly in low- and middle-income countries.


Subject(s)
COVID-19/immunology , COVID-19/therapy , Coronavirus Nucleocapsid Proteins/immunology , Horses/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/virology , Coronavirus Nucleocapsid Proteins/genetics , Coronavirus Nucleocapsid Proteins/metabolism , Enzyme-Linked Immunosorbent Assay , Humans , Immunization/methods , Immunization, Passive/methods , Immunoglobulin G/immunology , Recombinant Proteins/immunology , Recombinant Proteins/metabolism , SARS-CoV-2/metabolism , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
11.
Curr Opin Virol ; 48: 65-72, 2021 06.
Article in English | MEDLINE | ID: covidwho-1203009

ABSTRACT

Vaccines based on mRNA-containing lipid nanoparticles (LNPs) pioneered by Katalin Karikó and Drew Weissman at the University of Pennsylvania are a promising new vaccine platform used by two of the leading vaccines against coronavirus disease in 2019 (COVID-19). However, there are many questions regarding their mechanism of action in humans that remain unanswered. Here we consider the immunological features of LNP components and off-target effects of the mRNA, both of which could increase the risk of side effects. We suggest ways to mitigate these potential risks by harnessing dendritic cell (DC) biology.


Subject(s)
Dendritic Cells/immunology , Immunization/methods , Lipids , Nanoparticles , RNA, Messenger , Vaccines/classification , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Humans , Lipids/administration & dosage , Lipids/immunology , Nanoparticles/administration & dosage , Nanoparticles/metabolism , RNA, Messenger/administration & dosage , RNA, Messenger/immunology
12.
Value Health Reg Issues ; 24: 240-246, 2021 May.
Article in English | MEDLINE | ID: covidwho-1199117

ABSTRACT

OBJECTIVES: Vaccines are recognized as the most effective strategy for long-term prevention of coronavirus disease 2019 (COVID-19) because they can reduce morbidity and mortality. The purpose of the present study was to evaluate willingness to pay (WTP) for a future COVID-19 vaccination among young adults in Southern Vietnam. METHODS: A cross-sectional, descriptive, and analytic study was undertaken with data collected from a community-based survey in southern Vietnam for 2 weeks in May 2020. The contingent valuation method was used to estimate WTP for COVID-19 vaccine. The average amount that respondents were willing to pay for the vaccine was US$ 85.9 2 ± 69.01. RESULTS: We also found the differences in WTP according to sex, living area, monthly income, and the level of self-rated risk of COVID-19. CONCLUSION: Our findings possibly contribute to the implementation of a pricing policy when the COVID-19 vaccine is introduced in Vietnam.


Subject(s)
COVID-19 Vaccines/economics , Health Expenditures/standards , Immunization/economics , Patients/psychology , Adolescent , Adult , COVID-19 Vaccines/therapeutic use , Cross-Sectional Studies , Female , Health Care Costs/standards , Health Care Costs/statistics & numerical data , Health Expenditures/statistics & numerical data , Humans , Immunization/methods , Male , Middle Aged , Patients/statistics & numerical data , Vietnam
13.
PLoS Pathog ; 17(4): e1009064, 2021 04.
Article in English | MEDLINE | ID: covidwho-1197395

ABSTRACT

Vaccines of outstanding efficiency, safety, and public acceptance are needed to halt the current SARS-CoV-2 pandemic. Concerns include potential side effects caused by the antigen itself and safety of viral DNA and RNA delivery vectors. The large SARS-CoV-2 spike (S) protein is the main target of current COVID-19 vaccine candidates but can induce non-neutralizing antibodies, which might cause vaccination-induced complications or enhancement of COVID-19 disease. Besides, encoding of a functional S in replication-competent virus vector vaccines may result in the emergence of viruses with altered or expanded tropism. Here, we have developed a safe single round rhabdovirus replicon vaccine platform for enhanced presentation of the S receptor-binding domain (RBD). Structure-guided design was employed to build a chimeric minispike comprising the globular RBD linked to a transmembrane stem-anchor sequence derived from rabies virus (RABV) glycoprotein (G). Vesicular stomatitis virus (VSV) and RABV replicons encoding the minispike not only allowed expression of the antigen at the cell surface but also incorporation into the envelope of secreted non-infectious particles, thus combining classic vector-driven antigen expression and particulate virus-like particle (VLP) presentation. A single dose of a prototype replicon vaccine complemented with VSV G, VSVΔG-minispike-eGFP (G), stimulated high titers of SARS-CoV-2 neutralizing antibodies in mice, equivalent to those found in COVID-19 patients, and protected transgenic K18-hACE2 mice from COVID-19-like disease. Homologous boost immunization further enhanced virus neutralizing activity. The results demonstrate that non-spreading rhabdovirus RNA replicons expressing minispike proteins represent effective and safe alternatives to vaccination approaches using replication-competent viruses and/or the entire S antigen.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Immunization/methods , SARS-CoV-2/immunology , Vaccines, Virus-Like Particle/administration & dosage , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/virology , Female , HEK293 Cells , Humans , Mice , Mice, Inbred C57BL
14.
Expert Rev Vaccines ; 20(5): 623-634, 2021 05.
Article in English | MEDLINE | ID: covidwho-1118865

ABSTRACT

OBJECTIVE: Infectious disease emergencies like the 2013-2016 Ebola epidemic and the 2009 influenza and current SARS-CoV-2 pandemics illustrate that vaccines are now given to diverse populations with preexisting pathologies requiring pharmacological management. Many natural biomolecules (steroid hormones, fatty acids, vitamins) and ~60% of prescribed medications are processed by hepatic cytochrome P450 (CYP) 3A4. The objective of this work was to determine the impact of infection and vaccines on drug metabolism. METHODS: The impact of an adenovirus-based vaccine expressing Ebola glycoprotein (AdEBO) and H1N1 and H3N2 influenza viruses on hepatic CYP 3A4 and associated nuclear receptors was evaluated in human hepatocytes (HC-04 cells) and in mice. RESULTS: CYP3A activity was suppressed by 55% in mice 24 h after administration of mouse-adapted H1N1, while ˂10% activity remained in HC-04 cells after infection with H1N1 and H3N2 due to global suppression of cellular translation capacity, indicated by reduction (70%, H1N1, 56%, H3N2) of phosphorylated eukaryotic translation initiation factor 4e (eIF4E). AdEBO suppressed CYP3A activity in vivo (44%) and in vitro (26%) 24 hours after infection. CONCLUSION: As the clinical evaluation of vaccines for SARS-CoV-2 and other global pathogens rise, studies to evaluate the impact of new vaccines and emerging pathogens on CYP3A4 and other metabolic enzymes are warranted to avoid therapeutic failures that could further compromise the public health during infectious disease emergencies.


Subject(s)
Cytochrome P-450 CYP3A/metabolism , Hepatocytes/enzymology , Hepatocytes/metabolism , Liver/enzymology , Liver/metabolism , Pharmaceutical Preparations/metabolism , Animals , Cells, Cultured , Eukaryotic Initiation Factor-4E , Humans , Immunization/methods , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL
15.
PLoS One ; 16(2): e0246951, 2021.
Article in English | MEDLINE | ID: covidwho-1088760

ABSTRACT

INTRODUCTION: The global abrupt progression of the COVID-19 pandemic may disrupt critical life-saving services such as routine immunization (RI), thus increasing the susceptibility of countries to outbreaks of vaccine-preventable diseases (VPDs). Being endemic to several infectious diseases, Lebanon might be at increased risk of outbreaks as the utilization of RI services might have deteriorated due to the pandemic and the country's political unrest following the October 2019 uprising. The aim of this study was to assess the changes in the utilization of RI services in both the public and private sectors following the COVID-19 pandemic. METHODS: A self-administered cross-sectional survey was completed electronically, in April 2020, by 345 private pediatricians who are registered in professional associations of physicians in Lebanon and provide immunization services at their clinics. Means of the reported percentages of decrease in the utilization of vaccination services by pediatricians were calculated. As for the public sector, an examination of the monthly differences in the number of administered vaccine doses in addition to their respective percentages of change was performed. Adjustment for the distribution of RI services between the sectors was performed to calculate the national decrease rate. RESULTS: The utilization of vaccination services at the national level decreased by 31%. In the private sector, immunization services provision diminished by 46.9% mainly between February and April 2020. The highest decrease rates were observed for oral poliovirus vaccine (OPV) and hepatitis A, followed by measles and pneumococcal conjugate vaccines. The number of vaccine doses administered in the public sector decreased by 20%. The most prominent reductions were detected for the OPV and measles vaccines, and during October 2019 and March 2020. CONCLUSION: The substantial decrease in the utilization of RI as a result of the COVID-19 pandemic requires public health interventions to prevent future outbreaks of VPDs.


Subject(s)
Patient Acceptance of Health Care/statistics & numerical data , COVID-19/immunology , COVID-19/psychology , Cross-Sectional Studies , Female , Humans , Immunization/methods , Immunization/psychology , Immunization Programs/statistics & numerical data , Immunization Schedule , Infant , Lebanon/epidemiology , Male , Pandemics , Patient Acceptance of Health Care/psychology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Surveys and Questionnaires , Vaccination/statistics & numerical data , Vaccination Coverage/statistics & numerical data , Vaccines/administration & dosage
16.
FASEB J ; 35(3): e21409, 2021 03.
Article in English | MEDLINE | ID: covidwho-1083988

ABSTRACT

The COVID-19 pandemic has unfolded to be the most challenging global health crisis in a century. In 11 months since its first emergence, according to WHO, the causative infectious agent SARS-CoV-2 has infected more than 100 million people and claimed more than 2.15 million lives worldwide. Moreover, the world has raced to understand the virus and natural immunity and to develop vaccines. Thus, within a short 11 months a number of highly promising COVID-19 vaccines were developed at an unprecedented speed and are now being deployed via emergency use authorization for immunization. Although a considerable number of review contributions are being published, all of them attempt to capture only a specific aspect of COVID-19 or its therapeutic approaches based on ever-expanding information. Here, we provide a comprehensive overview to conceptually thread together the latest information on global epidemiology and mitigation strategies, clinical features, viral pathogenesis and immune responses, and the current state of vaccine development.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , COVID-19/prevention & control , Immunity/immunology , Pandemics/prevention & control , Animals , Humans , Immunization/methods , SARS-CoV-2/immunology
17.
Sci Rep ; 10(1): 22370, 2020 12 22.
Article in English | MEDLINE | ID: covidwho-997940

ABSTRACT

There are currently few approved effective treatments for SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Nanobodies are 12-15 kDa single-domain antibody fragments that can be delivered by inhalation and are amenable to relatively inexpensive large scale production compared to other biologicals. We have isolated nanobodies that bind to the SARS-CoV-2 spike protein receptor binding domain and block spike protein interaction with the angiotensin converting enzyme 2 (ACE2) with 1-5 nM affinity. The lead nanobody candidate, NIH-CoVnb-112, blocks SARS-CoV-2 spike pseudotyped lentivirus infection of HEK293 cells expressing human ACE2 with an EC50 of 0.3 µg/mL. NIH-CoVnb-112 retains structural integrity and potency after nebulization. Furthermore, NIH-CoVnb-112 blocks interaction between ACE2 and several high affinity variant forms of the spike protein. These nanobodies and their derivatives have therapeutic, preventative, and diagnostic potential.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Viral/immunology , Antibody Affinity , COVID-19/metabolism , Drug Discovery/methods , Protein Interaction Domains and Motifs/immunology , SARS-CoV-2/chemistry , Single-Domain Antibodies/immunology , Spike Glycoprotein, Coronavirus/chemistry , Angiotensin-Converting Enzyme 2/genetics , Animals , Antibodies, Neutralizing/immunology , Binding Sites, Antibody/immunology , COVID-19/therapy , COVID-19/virology , Camelids, New World , HEK293 Cells , Humans , Immunization/methods , Male , Protein Binding , Signal Transduction/genetics , Spike Glycoprotein, Coronavirus/genetics , Transduction, Genetic , Transfection
18.
Indian Pediatr ; 57(12): 1147-1152, 2020 Dec 15.
Article in English | MEDLINE | ID: covidwho-976776

ABSTRACT

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, immunization practices of all age groups, especially routine childhood vaccines, have been interrupted. Immunization is considered an essential health activity, which needs to be resumed as early as possible. This pandemic has created several unique issues related to routine immunization of individual children at clinics, which needs to be addressed. In this communication, the Advisory Committee on Vaccines and Immunization Practices (ACVIP) of Indian Academy of Pediatrics addresses the common questions and issues related to SARS-CoV-2 and routine immunization services. This also includes the recommendations for routine immunization of SARS-CoV-2 suspect and positive children, and for the logistics to be followed for immunization services.


Subject(s)
COVID-19 , Immunization Schedule , Immunization , Child , Humans , Immunization/methods , Immunization/standards , India , Pandemics , Practice Guidelines as Topic , SARS-CoV-2
19.
Saudi Med J ; 41(11): 1197-1203, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-903084

ABSTRACT

OBJECTIVES: To investigate whether the coronavirus disease-2019 pandemic has had any effects on pediatric vaccination rates at the main university hospital in Saudi Arabia. METHODS: A retrospective study conducted at King Saud University Medical City, Riyadh, Saudi Arabia using electronic health records. The vaccination statuses of all children who were scheduled for vaccinations at birth and at 2, 4, 6, 9, and 12 months during March, April and May between 2017 and 2020 were included in the study with total sample of 15,870 children, and comparisons between the cohorts were performed. RESULTS: All vaccination visits during April and May 2020 were below the lower extremes except for the birth vaccinations. In March, April, and May 2020 there were respective drops in vaccination visits of 49.93%, 71.90% and 68.48% compared with the mean numbers of vaccination visits during the same months from 2017 to 2019. In comparisons of mean numbers of visits from March 2017 to May 2019 and March to May in 2020, the respective reductions in visits for birth and 2, 4, 6, 9 and 12-month vaccinations were 16.5%, 80.5%, 74.7%, 72.9%, 80.0% and 74.1%. CONCLUSIONS: The huge impact of the coronavirus disease-2019 pandemic on childhood vaccinations will require urgent vaccination recovery plans with innovative approaches and future action plans to maintain vaccination coverage during any subsequent pandemics.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Immunization/statistics & numerical data , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Vaccination Coverage/statistics & numerical data , Age Factors , COVID-19 , Child, Preschool , Cohort Studies , Female , Hospitals, University , Humans , Immunization/methods , Incidence , Infant , Infant, Newborn , Male , Pandemics/statistics & numerical data , Retrospective Studies , Saudi Arabia/epidemiology , Sex Factors
20.
Sci Adv ; 6(45)2020 11.
Article in English | MEDLINE | ID: covidwho-842149

ABSTRACT

The current coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus genetically close to SARS-CoV. To investigate the effects of previous SARS-CoV infection on the ability to recognize and neutralize SARS-CoV-2, we analyzed 20 convalescent serum samples collected from individuals infected with SARS-CoV during the 2003 SARS outbreak. All patient sera reacted strongly with the S1 subunit and receptor binding domain (RBD) of SARS-CoV; cross-reacted with the S ectodomain, S1, RBD, and S2 proteins of SARS-CoV-2; and neutralized both SARS-CoV and SARS-CoV-2 S protein-driven infections. Analysis of antisera from mice and rabbits immunized with a full-length S and RBD immunogens of SARS-CoV verified cross-reactive neutralization against SARS-CoV-2. A SARS-CoV-derived RBD from palm civets elicited more potent cross-neutralizing responses in immunized animals than the RBD from a human SARS-CoV strain, informing strategies for development of universal vaccines against emerging coronaviruses.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Immunization/methods , SARS Virus/immunology , SARS-CoV-2/immunology , Severe Acute Respiratory Syndrome/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/virology , COVID-19 Vaccines/immunology , Cross Reactions , Follow-Up Studies , HEK293 Cells , Humans , Mice , Mice, Inbred BALB C , Neutralization Tests , Rabbits , Severe Acute Respiratory Syndrome/blood , Severe Acute Respiratory Syndrome/virology
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