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1.
J Immunol Methods ; 505: 113275, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1796490

ABSTRACT

Golden Syrian hamsters are increasingly used as a permissive animal model for SARS-CoV-2 virus studies, but the lack of immunological assays and other immunological reagents for hamsters limits its full potential. Herein, we developed an ELISA method to detect antibodies specific to peptides and proteins derived from SARS-CoV-2 virus in immunized golden Syrian hamsters. Under optimized conditions, this assay quantitates antibodies specific for individual viral peptides, peptide pools, and proteins. Hence, this ELISA method allows investigators to quantitatively assess humoral immune responses at the peptide and protein levels and has potential application in the development of peptide-based vaccines to be tested in hamsters.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Viral , Cricetinae , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Mesocricetus , Peptides
2.
Nature reviews. Immunology ; : 1-2, 2022.
Article in English | EuropePMC | ID: covidwho-1697256

ABSTRACT

Vaccines have outstanding efficacy and safety records, and the evolving science of vaccines is enabling us to better understand their mechanisms of action as well as the pathways that drive vaccine-related adverse events. This understanding is particularly crucial as novel vaccine antigens, platforms and adjuvants are increasingly being used. In this Comment article, Gregory Poland and Richard Kennedy outline the importance of continued funding and infrastructure support for research into vaccine safety to inform public health decisions and increase public trust in new vaccine technologies.

3.
J Infect Dis ; 2022 Feb 08.
Article in English | MEDLINE | ID: covidwho-1684708

ABSTRACT

The durability of protective humoral immunity after SARS-CoV-2 vaccination and infection is largely dependent on the generation and persistence of antigen-specific isotype-switched memory B cells (MBCs) and long-lived plasma cells that reside in the bone marrow and secrete high-affinity neutralizing antibodies. The reactivity of vaccine-induced MBCs to emerging clinically significant SARS-CoV-2 variants of concern (VoCs) is largely unknown. In a longitudinal cohort study (up to 6 months following COVID-19 mRNA vaccination) we measured MBCs in concert with other functional antibody measures. We found statistically significant differences between the frequencies of MBCs responding to homologous and VoC receptor-binding domain/RBDs (Beta, Gamma, and Delta) after vaccination that persisted over time. In concert with a waning antibody response, the reduced MBC response to VoCs could translate to a weaker subsequent recall immune response and increased susceptibility to the emerging SARS-CoV-2 variant strains after vaccination.

4.
Lancet ; 399(10321): 212-213, 2022 01 15.
Article in English | MEDLINE | ID: covidwho-1665563
5.
Microbiol Spectr ; 9(2): e0141621, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1495015

ABSTRACT

The rapid worldwide spread of SARS-CoV-2 has accelerated research and development for controlling the COVID-19 pandemic. A multi-coronavirus protein microarray was created containing full-length proteins, overlapping protein fragments of various lengths, and peptide libraries from SARS-CoV-2 and four other human coronaviruses. Sera from confirmed COVID-19 patients as well as unexposed individuals were applied to multicoronavirus arrays to identify specific antibody reactivity. High-level IgG, IgM, and IgA reactivity to structural proteins S, M, and N of SARS-CoV-2, as well as accessory proteins such as ORF3a and ORF7a, were observed that were specific to COVID-19 patients. Antibody reactivity against overlapping 100-, 50-, and 30-amino acid fragments of SARS-CoV-2 proteins was used to identify antigenic regions. Numerous proteins of SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), and the endemic human coronaviruses HCoV-NL63 and HCoV-OC43 were also more reactive with IgG, IgM, and IgA in COVID-19 patient sera than in unexposed control sera, providing further evidence of immunologic cross-reactivity between these viruses. Whereas unexposed individuals had minimal reactivity against SARS-CoV-2 proteins that poorly correlated with reactivity against HCoV-NL63 and HCoV-OC43 S2 and N proteins, COVID-19 patient sera had higher correlation between SARS-CoV-2 and HCoV responses, suggesting that de novo antibodies against SARS-CoV-2 cross-react with HCoV epitopes. Array responses were compared with validated spike protein-specific IgG enzyme-linked immunosorbent assays (ELISAs), showing agreement between orthologous methods. SARS-CoV-2 microneutralization titers were low in the COVID-19 patient sera but correlated with array responses against S and N proteins. The multi-coronavirus protein microarray is a useful tool for mapping antibody reactivity in COVID-19 patients. IMPORTANCE With novel mutant SARS-CoV-2 variants of concern on the rise, knowledge of immune specificities against SARS-CoV-2 proteins is increasingly important for understanding the impact of structural changes in antibody-reactive protein epitopes on naturally acquired and vaccine-induced immunity, as well as broader topics of cross-reactivity and viral evolution. A multi-coronavirus protein microarray used to map the binding of COVID-19 patient antibodies to SARS-CoV-2 proteins and protein fragments as well as to the proteins of four other coronaviruses that infect humans has shown specific regions of SARS-CoV-2 proteins that are highly reactive with patient antibodies and revealed cross-reactivity of these antibodies with other human coronaviruses. These data and the multi-coronavirus protein microarray tool will help guide further studies of the antibody response to COVID-19 and to vaccination against this worldwide pandemic.


Subject(s)
Antibodies, Viral/immunology , Coronavirus NL63, Human/immunology , Coronavirus OC43, Human/immunology , Epitopes/immunology , Middle East Respiratory Syndrome Coronavirus/immunology , SARS-CoV-2/immunology , Antibodies, Viral/blood , Binding Sites, Antibody/immunology , COVID-19/immunology , Coronavirus Nucleocapsid Proteins/immunology , Cross Reactions/immunology , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Phosphoproteins/immunology , Protein Array Analysis , Spike Glycoprotein, Coronavirus/immunology , Viral Proteins/immunology , Viroporin Proteins/immunology
6.
J Allergy Clin Immunol Pract ; 9(10): 3599-3603, 2021 10.
Article in English | MEDLINE | ID: covidwho-1363230

ABSTRACT

Influenza is an annual seasonal epidemic, and occasionally pandemic, respiratory disease that causes considerable morbidity and mortality worldwide. Despite the widespread availability of safe and effective vaccines since the 1950s, this virus continues to pose a significant public health threat. Variable and often weak vaccine effectiveness, antigenic drift and shift, and vaccine hesitancy are some of the obstacles that must be overcome to control this disease. In this article, we briefly review current influenza vaccines, address safety concerns and the need for newer influenza vaccines of higher efficacy, and discuss efforts to create broadly protective, universal influenza vaccines.


Subject(s)
Influenza Vaccines , Influenza, Human , Humans , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Pandemics
7.
Clin Pharmacol Ther ; 110(3): 546-548, 2021 09.
Article in English | MEDLINE | ID: covidwho-1372710
10.
Immunol Rev ; 296(1): 205-219, 2020 07.
Article in English | MEDLINE | ID: covidwho-998975

ABSTRACT

This article provides a review of studies evaluating the role of host (and viral) genetics (including variation in HLA genes) in the immune response to coronaviruses, as well as the clinical outcome of coronavirus-mediated disease. The initial sections focus on seasonal coronaviruses, SARS-CoV, and MERS-CoV. We then examine the state of the knowledge regarding genetic polymorphisms and SARS-CoV-2 and COVID-19. The article concludes by discussing research areas with current knowledge gaps and proposes several avenues for future scientific exploration in order to develop new insights into the immunology of SARS-CoV-2.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Disease Resistance/genetics , Genetic Predisposition to Disease , Host-Pathogen Interactions/genetics , Pneumonia, Viral/immunology , Animals , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/genetics , Coronavirus Infections/virology , Host-Pathogen Interactions/immunology , Humans , Middle East Respiratory Syndrome Coronavirus/immunology , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/genetics , Pneumonia, Viral/virology , SARS Virus/immunology , SARS Virus/pathogenicity , SARS-CoV-2 , Severe Acute Respiratory Syndrome/genetics , Severe Acute Respiratory Syndrome/virology
11.
Vaccine ; 38(51): 8185-8193, 2020 12 03.
Article in English | MEDLINE | ID: covidwho-997580

ABSTRACT

BACKGROUND: While administration of the measles-mumps-rubella (MMR-II®) vaccine has been effective at preventing rubella infection in the United States, the durability of humoral immunity to the rubella component of MMR vaccine has not been widely studied among older adolescents and adults. METHODS: In this longitudinal study, we sought to assess the durability of rubella virus (RV)-specific humoral immunity in a healthy population (n = 98) of adolescents and young adults at two timepoints: ~7 and ~17 years after two doses of MMR-II® vaccination. Levels of circulating antibodies specific to RV were measured by ELISA and an immune-colorimetric neutralization assay. RV-specific memory B cell responses were also measured by ELISpot. RESULTS: Rubella-specific IgG antibody titers, neutralizing antibody titers, and memory B cell responses declined with increasing time since vaccination; however, these decreases were relatively moderate. Memory B cell responses exhibited a greater decline in men compared to women. CONCLUSIONS: Collectively, rubella-specific humoral immunity declines following vaccination, although subjects' antibody titers remain well above the currently recognized threshold for protective immunity. Clinical correlates of protection based on neutralizing antibody titer and memory B cell ELISpot response should be defined.


Subject(s)
Immunity, Humoral , Measles-Mumps-Rubella Vaccine/immunology , Rubella/immunology , Adolescent , Adult , Antibodies, Neutralizing/immunology , B-Lymphocytes/immunology , Female , Humans , Immunoglobulin G/blood , Male , Measles-Mumps-Rubella Vaccine/pharmacology , Rubella/prevention & control , Time Factors , Vaccination , Young Adult
12.
Vaccine ; 38(50): 7897-7904, 2020 11 25.
Article in English | MEDLINE | ID: covidwho-912658

ABSTRACT

INTRODUCTION: Rubella virus (RV) was eliminated in the United States in 2004, although a small portion of the population fails to develop long-term immunity against RV even after two doses of the measles-mumps-rubella (MMR) vaccine. We hypothesized that inherent biological differences in cytokine and chemokine signaling likely govern an individual's response to a third dose of the vaccine. METHODS: Healthy young women (n = 97) were selected as study participants if they had either low or high extremes of RV-specific antibody titer after two previous doses of MMR vaccine. We measured cytokine and chemokine secretion from RV-stimulated PBMCs before and 28 days after they received a third dose of MMR vaccine and assessed correlations with humoral immune response outcomes. RESULTS: High and low antibody vaccine responders exhibited a strong pro-inflammatory cellular response, with an underlying Th1-associated signature (IL-2, IFN-γ, MIP-1ß, IP-10) and suppressed production of most Th2-associated cytokines (IL-4, IL-10, IL-13). IL-10 and IL-4 exhibited significant negative associations with neutralizing antibody titers and memory B cell ELISpot responses among low vaccine responders. CONCLUSION: IL-4 and IL-10 signaling pathways may be potential targets for understanding and improving the immune response to rubella vaccination or for designing new vaccines that induce more durable immunity.


Subject(s)
Immunity, Cellular , Immunity, Humoral , Measles-Mumps-Rubella Vaccine/administration & dosage , Measles-Mumps-Rubella Vaccine/immunology , Rubella/immunology , Adult , Chemokines/immunology , Chemokines/metabolism , Cytokines/immunology , Cytokines/metabolism , Female , Humans , Immunization Schedule , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Middle Aged , Rubella/prevention & control , Young Adult
13.
Lancet ; 396(10262): 1595-1606, 2020 11 14.
Article in English | MEDLINE | ID: covidwho-857279

ABSTRACT

Understanding immune responses to severe acute respiratory syndrome coronavirus 2 is crucial to understanding disease pathogenesis and the usefulness of bridge therapies, such as hyperimmune globulin and convalescent human plasma, and to developing vaccines, antivirals, and monoclonal antibodies. A mere 11 months ago, the canvas we call COVID-19 was blank. Scientists around the world have worked collaboratively to fill in this blank canvas. In this Review, we discuss what is currently known about human humoral and cellular immune responses to severe acute respiratory syndrome coronavirus 2 and relate this knowledge to the COVID-19 vaccines currently in phase 3 clinical trials.


Subject(s)
Betacoronavirus , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/pharmacology , COVID-19 , COVID-19 Vaccines , Clinical Trials, Phase III as Topic , Coronavirus Infections/immunology , Humans , Pneumonia, Viral/immunology , SARS-CoV-2
14.
Mayo Clin Proc ; 95(10): 2172-2188, 2020 10.
Article in English | MEDLINE | ID: covidwho-813735

ABSTRACT

In the midst of the severe acute respiratory syndrome coronavirus 2 pandemic and its attendant morbidity and mortality, safe and efficacious vaccines are needed that induce protective and long-lived immune responses. More than 120 vaccine candidates worldwide are in various preclinical and phase 1 to 3 clinical trials that include inactivated, live-attenuated, viral-vectored replicating and nonreplicating, protein- and peptide-based, and nucleic acid approaches. Vaccines will be necessary both for individual protection and for the safe development of population-level herd immunity. Public-private partnership collaborative efforts, such as the Accelerating COVID-19 Therapeutic Interventions and Vaccines mechanism, are key to rapidly identifying safe and effective vaccine candidates as quickly and efficiently as possible. In this article, we review the major vaccine approaches being taken and issues that must be resolved in the quest for vaccines to prevent coronavirus disease 2019. For this study, we scanned the PubMed database from 1963 to 2020 for all publications using the following search terms in various combinations: SARS, MERS, COVID-19, SARS-CoV-2, vaccine, clinical trial, coronavirus, pandemic, and vaccine development. We also did a Web search for these same terms. In addition, we examined the World Health Organization, Centers for Disease Control and Prevention, and other public health authority websites. We excluded abstracts and all articles that were not written in English.


Subject(s)
Betacoronavirus , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/therapeutic use , COVID-19 , COVID-19 Vaccines , Clinical Laboratory Techniques/methods , Humans , Public Health , SARS-CoV-2 , United States
15.
Sci Rep ; 10(1): 14179, 2020 08 25.
Article in English | MEDLINE | ID: covidwho-741695

ABSTRACT

A novel coronavirus (SARS-CoV-2) emerged from China in late 2019 and rapidly spread across the globe, infecting millions of people and generating societal disruption on a level not seen since the 1918 influenza pandemic. A safe and effective vaccine is desperately needed to prevent the continued spread of SARS-CoV-2; yet, rational vaccine design efforts are currently hampered by the lack of knowledge regarding viral epitopes targeted during an immune response, and the need for more in-depth knowledge on betacoronavirus immunology. To that end, we developed a computational workflow using a series of open-source algorithms and webtools to analyze the proteome of SARS-CoV-2 and identify putative T cell and B cell epitopes. Utilizing a set of stringent selection criteria to filter peptide epitopes, we identified 41 T cell epitopes (5 HLA class I, 36 HLA class II) and 6 B cell epitopes that could serve as promising targets for peptide-based vaccine development against this emerging global pathogen. To our knowledge, this is the first study to comprehensively analyze all 10 (structural, non-structural and accessory) proteins from SARS-CoV-2 using predictive algorithms to identify potential targets for vaccine development.


Subject(s)
Betacoronavirus/immunology , Computational Biology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Epitopes, B-Lymphocyte/immunology , Epitopes, T-Lymphocyte/immunology , Host-Pathogen Interactions/immunology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Viral Proteins/immunology , Amino Acid Sequence , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Betacoronavirus/classification , Betacoronavirus/genetics , Betacoronavirus/metabolism , COVID-19 , Computational Biology/methods , Coronavirus Infections/metabolism , Epitopes, B-Lymphocyte/chemistry , Epitopes, T-Lymphocyte/chemistry , Genome, Viral , Genomics/methods , Humans , Models, Molecular , Pandemics , Peptides/chemistry , Peptides/immunology , Phylogeny , Pneumonia, Viral/metabolism , SARS-CoV-2 , Structure-Activity Relationship , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Vaccines, Subunit/immunology , Viral Proteins/chemistry , Viral Vaccines/immunology
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