The SARS-CoV-2 virus emerged in December 2019 and has caused a worldwide pandemic due to the lack of any pre-existing immunity. Accurate serology testing is urgently needed to help diagnose ...infection, determine past exposure of populations and assess the response to a future vaccine. The landscape of antibody responses to SARS-CoV-2 is unknown. In this study, we utilized the luciferase immunoprecipitation system to assess the antibody responses to 15 different SARS-CoV-2 antigens in patients with COVID-19. We identified new targets of the immune response to SARS-CoV-2 and show that nucleocapsid, open reading frame (ORF)8 and ORF3b elicit the strongest specific antibody responses. ORF8 and ORF3b antibodies, taken together as a cluster of points, identified 96.5% of COVID-19 samples at early and late time points of disease with 99.5% specificity. Our findings could be used to develop second-generation diagnostic tests to improve serological assays for COVID-19 and are important in understanding pathogenicity.
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has now become a pandemic, but there is currently very little understanding ...of the antigenicity of the virus. We therefore determined the crystal structure of CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient, in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein at 3.1-angstrom resolution. CR3022 targets a highly conserved epitope, distal from the receptor binding site, that enables cross-reactive binding between SARS-CoV-2 and SARS-CoV. Structural modeling further demonstrates that the binding epitope can only be accessed by CR3022 when at least two RBDs on the trimeric S protein are in the "up" conformation and slightly rotated. These results provide molecular insights into antibody recognition of SARS-CoV-2.
The Omicron variant is rapidly becoming the dominant SARS-CoV-2 virus circulating globally. It is important to define reductions in virus neutralizing activity in the serum of convalescent or ...vaccinated individuals to understand potential loss of protection against infection by Omicron. We previously established that a 50% plaque reduction neutralization antibody titer (PRNT
) ≥25.6 in our live virus assay corresponded to the threshold for 50% protection from infection against wild-type (WT) SARS-CoV-2. Here we show markedly reduced serum antibody titers against the Omicron variant (geometric mean titer (GMT) < 10) compared to WT virus 3-5 weeks after two doses of BNT162b2 (GMT = 218.8) or CoronaVac vaccine (GMT = 32.5). A BNT162b2 booster dose elicited Omicron PRNT
titers ≥25.6 in 88% of individuals (22 of 25) who previously received 2 doses of BNT162b2 and 80% of individuals (24 of 30) who previously received CoronaVac. However, few (3%) previously infected individuals (1 of 30) or those vaccinated with three doses of CoronaVac (1 of 30) met this threshold. Our findings suggest that countries primarily using CoronaVac vaccines should consider messenger RNA vaccine boosters in response to the spread of Omicron. Studies evaluating the effectiveness of different vaccines against the Omicron variant are urgently needed.
To the Editor:
Multiple reassortant strains of novel, highly pathogenic avian influenza A(H5) viruses in clade 2.3.4.4 have recently emerged and spread in Asia, Europe, and North America, giving rise ...to multiple subtypes (H5N2, H5N5, H5N6, and H5N8).
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We report on a 59-year-old man in Guangzhou, China, with influenza A(H5N6) infection and associated illness. He had a 30-year history of smoking and had stopped smoking in January 2014. He had undergone surgery and chemotherapy for colon cancer, the last chemotherapy dose having been administered in April 2014. During the weeks before illness onset, he regularly purchased and handled live . . .
BackgroundThe ongoing coronavirus disease (COVID-19) pandemic has major impacts on health systems, the economy and society. Assessing infection attack rates in the population is critical for ...estimating disease severity and herd immunity which is needed to calibrate public health interventions. We have previously shown that it is possible to achieve this in real time to impact public health decision making.AimOur objective was to develop and evaluate serological assays applicable in large-scale sero-epidemiological studies.MethodsWe developed an ELISA to detect IgG and IgM antibodies to the receptor-binding domain (RBD) of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated its sensitivity and specificity in combination with confirmatory microneutralisation (MN) and 90% plaque reduction neutralisation tests (PRNT
) in 51 sera from 24 patients with virologically confirmed COVID-19 and in age-stratified sera from 200 healthy controls.ResultsIgG and IgM RBD ELISA, MN and PRNT
were reliably positive after 29 days from illness onset with no detectable cross-reactivity in age-stratified controls. We found that PRNT
tests were more sensitive in detecting antibody than MN tests carried out with the conventional 100 tissue culture infectious dose challenge. Heparinised plasma appeared to reduce the infectivity of the virus challenge dose and may confound interpretation of neutralisation test.ConclusionUsing IgG ELISA based on the RBD of the spike protein to screen sera for SARS-CoV-2 antibody, followed by confirmation using PRNT
, is a valid approach for large-scale sero-epidemiology studies.
The World Health Organization has declared the ongoing outbreak of COVID-19, which is caused by a novel coronavirus SARS-CoV-2, a pandemic. There is currently a lack of knowledge about the antibody ...response elicited from SARS-CoV-2 infection. One major immunological question concerns antigenic differences between SARS-CoV-2 and SARS-CoV. We address this question by analyzing plasma from patients infected by SARS-CoV-2 or SARS-CoV and from infected or immunized mice. Our results show that, although cross-reactivity in antibody binding to the spike protein is common, cross-neutralization of the live viruses may be rare, indicating the presence of a non-neutralizing antibody response to conserved epitopes in the spike. Whether such low or non-neutralizing antibody response leads to antibody-dependent disease enhancement needs to be addressed in the future. Overall, this study not only addresses a fundamental question regarding antigenicity differences between SARS-CoV-2 and SARS-CoV but also has implications for immunogen design and vaccine development.
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•Cross-reactive antigen binding is common between SARS-CoV and SARS-CoV-2•Cross-reactive antibody responses target both RBD and non-RBD regions•Cross-neutralization of live viruses may be rare between SARS-CoV and SARS-CoV-2
Lv et al. examine the antibody responses from patients infected by SARS-CoV-2 or SARS-CoV and from infected or immunized mice. The results show that cross-reactive binding to the spike protein is common, whereas cross-neutralization of the live viruses may be rare.
Egg-adaptive mutations in influenza hemagglutinin (HA) often emerge during the production of egg-based seasonal influenza vaccines, which contribute to the largest share in the global influenza ...vaccine market. While some egg-adaptive mutations have minimal impact on the HA antigenicity (e.g. G186V), others can alter it (e.g. L194P). Here, we show that the preference of egg-adaptive mutation in human H3N2 HA is strain-dependent. In particular, Thr160 and Asn190, which are found in many recent H3N2 strains, restrict the emergence of L194P but not G186V. Our results further suggest that natural amino acid variants at other HA residues also play a role in determining the preference of egg-adaptive mutation. Consistently, recent human H3N2 strains from different clades acquire different mutations during egg passaging. Overall, these results demonstrate that natural mutations in human H3N2 HA can influence the preference of egg-adaptation mutation, which has important implications in seed strain selection for egg-based influenza vaccine.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
8.
COVID‐19 vaccines: Knowing the unknown Lv, Huibin; Wu, Nicholas C.; Mok, Chris K. P.
European journal of immunology,
July 2020, Letnik:
50, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Vaccine development against SARS‐CoV‐2 has drawn attention around the globe due to the exploding pandemic. Although COVID‐19 is caused by a new coronavirus, SARS‐CoV‐2, previous research on other ...coronavirus vaccines, such as FIPV, SARS, and MERS, has provided valuable information for the rapid development of COVID‐19 vaccine. However, important knowledge gaps remain — some are specific to SARS‐CoV‐2, others are fundamental to immunology and vaccinology. Here, we discuss areas that need to be addressed for COVID‐19 vaccine development, and what can be learned from examples of vaccine development in the past. Since the beginning of the outbreak, the research progress on COVID‐19 has been remarkable. We are therefore optimistic about the rapid development of COVID‐19 vaccine.
An ideal COVID‐19 vaccine should offer long‐term protection with no adverse effect. The current status of COVID‐19 vaccine development and factors that need to be considered are discussed.
Since their first isolation in 2013, influenza A/H5N6 viruses have spread amongst poultry across multiple provinces in China and to Laos, Vietnam and Myanmar. So far, there have been 14 human H5N6 ...infections with 10 fatalities.We investigated the tropism, replication competence and cytokine induction of one human and two avian H5N6 isolates in
and
cultures derived from the human respiratory tract. Virus tropism and replication were studied in
cultures of human nasopharynx, bronchus and lung. Induction of cytokines and chemokines was measured
in virus-infected primary human alveolar epithelial cells.Human H5N6 virus replicated more efficiently than highly pathogenic avian influenza (HPAI) H5N1 virus and as efficiently as H1N1pdm in
human bronchus and lung and was also able to replicate in
cultures of human nasopharynx. Avian H5N6 viruses replicated less efficiently than H1N1pdm in human bronchial tissues and to similar titres as HPAI H5N1 in the lung. While the human H5N6 virus had affinity for avian-like receptors, the two avian isolates had binding affinity for both avian- and human-like receptors. All three H5N6 viruses were less potent inducers of pro-inflammatory cytokines compared with H5N1 virus.Human H5N6 virus appears better adapted to infect the human airways than H5N1 virus and may pose a significant public health threat.
The antibody response magnitude and kinetics may impact clinical severity, serological diagnosis and long-term protection of COVID-19, which may play a role in why children experience lower ...morbidity. We therefore tested samples from 122 children in Hong Kong with symptomatic (n = 78) and asymptomatic (n = 44) SARS-CoV-2 infections up to 200 days post infection, relative to 71 infected adults (symptomatic n = 61, and asymptomatic n = 10), and negative controls (n = 48). We assessed serum IgG antibodies to a 14-wide antigen panel of structural and accessory proteins by Luciferase Immuno-Precipitation System (LIPS) assay and circulating cytokines. Infected children have lower levels of Spike, Membrane, ORF3a, ORF7a, ORF7b antibodies, comparable ORF8 and elevated E-specific antibodies than adults. Combination of two unique antibody targets, ORF3d and ORF8, can accurately discriminate SARS-CoV-2 infection in children. Principal component analysis reveals distinct pediatric serological signatures, and the highest contribution to variance from adults are antibody responses to non-structural proteins ORF3d, NSP1, ORF3a and ORF8. From a diverse panel of cytokines that can modulate immune priming and relative inflammation, IL-8, MCP-1 and IL-6 correlate with the magnitude of pediatric antibody specificity and severity. Antibodies to SARS-CoV-2 internal proteins may become an important sero surveillance tool of infection with the roll-out of vaccines in the pediatric population.
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