scholarly journals Differences in Antibody Kinetics and Functionality Between Severe and Mild Severe Acute Respiratory Syndrome Coronavirus 2 Infections

2020 ◽  
Vol 222 (8) ◽  
pp. 1265-1269 ◽  
Author(s):  
Ger Rijkers ◽  
Jean-Luc Murk ◽  
Bas Wintermans ◽  
Bieke van Looy ◽  
Marcel van den Berge ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Antibody Response ◽  
Geometric Mean ◽  
Severe Disease ◽  
Immunoglobulin A ◽  
Virus Neutralization ◽  
Neutralization Titer ◽  
Humoral Immune ◽  
Leave Of Absence ◽  
Antibody Kinetics

Abstract We determined and compared the humoral immune response in patients with severe (hospitalized) and mild (nonhospitalized) coronavirus disease 2019 (COVID-19). Patients with severe disease (n = 38) develop a robust antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including immunoglobulin G and immunoglobulin A antibodies. The geometric mean 50% virus neutralization titer is 1:240. SARS-CoV-2 infection was found in hospital personnel (n = 24), who developed mild symptoms necessitating leave of absence and self-isolation, but not hospitalization; 75% developed antibodies, but with low/absent virus neutralization (60% with titers <1:20). While severe COVID-19 patients develop a strong antibody response, mild SARS-CoV-2 infections induce a modest antibody response. Long-term monitoring will show whether these responses predict protection against future infections.

scholarly journals Differences in antibody kinetics and functionality between severe and mild SARS-CoV-2 infections

2020 ◽  
Author(s):  
Ger Rijkers ◽  
Jean-Luc Murk ◽  
Bas Wintermans ◽  
Bieke van Looy ◽  
Marcel van den Berge ◽  
...  
Keyword(s):  
Antibody Response ◽  
Geometric Mean ◽  
Virus Neutralization ◽  
Neutralization Titer ◽  
Humoral Immune ◽  
Leave Of Absence ◽  
Antibody Kinetics ◽  
Virus Neutralization Titer ◽  
Term Monitoring

AbstractWe determined and compared the humoral immune response in severe, hospitalized and mild, non-hospitalized COVID-19 patients. Severe patients (n=38) develop a robust antibody response to SARS-CoV-2, including IgG and IgA antibodies. The geometric mean 50% virus neutralization titer is 1:240. SARS-CoV-2 infected hospital personnel (n=24), who developed mild symptoms necessitating leave of absence, self-isolation, but not hospitalization, 75 % develop antibodies, but with low/absent virus neutralization (60% < 1:20).While severe COVID-19 patients develop a strong antibody response, mild SARS-CoV-2 infections induce a modest antibody response. Long term monitoring will show whether these responses predict protection against future infections.

scholarly journals Immunological imprinting of the antibody response in COVID-19 patients

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Teresa Aydillo ◽  
Alexander Rombauts ◽  
Daniel Stadlbauer ◽  
Sadaf Aslam ◽  
Gabriela Abelenda-Alonso ◽  
...  
Keyword(s):  
Immune Response ◽  
Severe Acute Respiratory Syndrome ◽  
Antibody Response ◽  
Humoral Immune Response ◽  
Nucleocapsid Protein ◽  
Spike Protein ◽  
Ongoing Research ◽  
Variable Regions ◽  
Humoral Immune ◽  
Human Coronaviruses

AbstractIn addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans are also susceptible to six other coronaviruses, for which consecutive exposures to antigenically related and divergent seasonal coronaviruses are frequent. Despite the prevalence of COVID-19 pandemic and ongoing research, the nature of the antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here we longitudinally profile the early humoral immune response against SARS-CoV-2 in hospitalized coronavirus disease 2019 (COVID-19) patients and quantify levels of pre-existing immunity to OC43, HKU1 and 229E seasonal coronaviruses, and find a strong back-boosting effect to conserved but not variable regions of OC43 and HKU1 betacoronaviruses spike protein. However, such antibody memory boost to human coronaviruses negatively correlates with the induction of IgG and IgM against SARS-CoV-2 spike and nucleocapsid protein. Our findings thus provide evidence of immunological imprinting by previous seasonal coronavirus infections that can potentially modulate the antibody profile to SARS-CoV-2 infection.

scholarly journals Immunological Evaluation and Comparison of Different EV71 Vaccine Candidates

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Ai-Hsiang Chou ◽  
Chia-Chyi Liu ◽  
Jui-Yuan Chang ◽  
Shu-Pei Lien ◽  
Meng-Shin Guo ◽  
...  
Keyword(s):  
Antibody Response ◽  
Enterovirus 71 ◽  
Neutralizing Antibody ◽  
Cost Effective ◽  
Virus Neutralization ◽  
Neutralization Titer ◽  
Mouth Diseases ◽  
Causative Agents ◽  
Immunological Evaluation ◽  
Virus Neutralization Titer

Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are major causative agents of hand, foot, and mouth diseases (HFMDs), and EV71 is now recognized as an emerging neurotropic virus in Asia. Effective medications and/or prophylactic vaccines against HFMD are not available. The current results from mouse immunogenicity studies using in-house standardized RD cell virus neutralization assays indicate that (1) VP1 peptide (residues 211–225) formulated with Freund’s adjuvant (CFA/IFA) elicited low virus neutralizing antibody response (1/32 titer); (2) recombinant virus-like particles produced from baculovirus formulated with CFA/IFA could elicit good virus neutralization titer (1/160); (3) individual recombinant EV71 antigens (VP1, VP2, and VP3) formulated with CFA/IFA, only VP1 elicited antibody response with 1/128 virus neutralization titer; and (4) the formalin-inactivated EV71 formulated in alum elicited antibodies that cross-neutralized different EV71 genotypes (1/640), but failed to neutralize CVA16. In contrast, rabbits antisera could cross-neutralize strongly against different genotypes of EV71 but weakly against CVA16, with average titers 1/6400 and 1/32, respectively. The VP1 amino acid sequence dissimilarity between CVA16 and EV71 could partially explain why mouse antibodies failed to cross-neutralize CVA16. Therefore, the best formulation for producing cost-effective HFMD vaccine is a combination of formalin-inactivated EV71 and CAV16 virions.

scholarly journals Predominance of Serotype-Specific Mucosal Antibody Response in Shigella flexneri-Infected Humans Living in an Area of Endemicity

2001 ◽  
Vol 69 (9) ◽  
pp. 5230-5234 ◽  
Author(s):  
Voahangy Rasolofo-Razanamparany ◽  
Anne-Marie Cassel-Beraud ◽  
Jean Roux ◽  
Philippe J. Sansonetti ◽  
Armelle Phalipon
Keyword(s):  
Antibody Response ◽  
Natural Infection ◽  
Shigella Flexneri ◽  
Immunoglobulin A ◽  
Cross Reactivity ◽  
Bacterial Antigen ◽  
Humoral Immune ◽  
Mucosal Antibody ◽  
Iga Antibody ◽  
Antibody Secreting Cells

ABSTRACT The mucosal humoral immune response elicited followingShigella flexneri infection in patients living in Antananarivo districts (Madagascar Island) was evaluated by measuring the gut-derived, circulating immunoglobulin A (IgA) antibody-secreting cells (ASC) specific for the major bacterial antigen lipopolysaccharide (LPS). Fifty, 34, 11, and 5% of the S. flexneri-positive patients were infected with serotypes 2a, 1a, 4a, and 3a, respectively. The total number of IgA ASC in infected patients increased significantly, compared to the number in healthy controls, early after the onset of disease. The number of anti-homologous LPS IgA ASC varied among individuals and peaked between days 5 and 10 after the onset of the disease. In the S. flexneri 1a- and 2a-infected patients, the level of IgA ASC cross-reactivity to heterologous S. flexneri serotypes was weak. These data indicate that S. flexneri 2a and 1a are the predominant strains responsible for shigellosis in this area of endemicity and that the anti-LPS antibody response following natural infection is mainly directed against serotype-specific determinants.

scholarly journals Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population

2020 ◽  
Author(s):  
Sabra L. Klein ◽  
Andrew Pekosz ◽  
Han-Sol Park ◽  
Rebecca L. Ursin ◽  
Janna R. Shapiro ◽  
...  
Keyword(s):  
Antibody Response ◽  
Neutralizing Antibody ◽  
Neutralization Assay ◽  
Antibody Responses ◽  
Full Length ◽  
Neutralization Titer ◽  
Humoral Immune ◽  
Virus Neutralization Assay ◽  
Male Sex ◽  
Substantial Heterogeneity

AbstractConvalescent plasma is currently one of the leading treatments for COVID-19, but there is a paucity of data identifying therapeutic efficacy. A comprehensive analysis of the antibody responses in potential plasma donors and an understanding of the clinical and demographic factors that drive variant antibody responses is needed. Among 126 potential convalescent plasma donors, the humoral immune response was evaluated by a SARS-CoV-2 virus neutralization assay using Vero-E6-TMPRSS2 cells, commercial IgG and IgA ELISA to Spike (S) protein S1 domain (Euroimmun), IgA, IgG and IgM indirect ELISAs to the full-length S or S-receptor binding domain (S-RBD), and an IgG avidity assay. Multiple linear regression and predictive models were utilized to assess the correlations between antibody responses with demographic and clinical characteristics. IgG titers were greater than either IgM or IgA for S1, full length S, and S-RBD in the overall population. Of the 126 plasma samples, 101 (80%) had detectable neutralizing titers. Using neutralization titer as the reference, the sensitivity of the IgG ELISAs ranged between 95-98%, but specificity was only 20-32%. Male sex, older age, and hospitalization with COVID-19 were all consistently associated with increased antibody responses across the serological assays. Neutralizing antibody titers were reduced over time in contrast to overall antibody responses. There was substantial heterogeneity in the antibody response among potential convalescent plasma donors, but sex, age and hospitalization emerged as factors that can be used to identify individuals with a high likelihood of having strong antiviral antibody levels.One Sentence SummaryThere is substantial heterogeneity in the antibody response to SARS-CoV-2 infection, with greater antibody responses being associated with male sex, advancing age, and hospitalization with COVID-19.

scholarly journals Omicron infection enhances neutralizing immunity against the Delta variant

2021 ◽  
Author(s):  
Khadija Khan ◽  
Farina Karim ◽  
Sandile Cele ◽  
Houriiyah Tegally ◽  
James Emmanuel San ◽  
...  
Keyword(s):  
South Africa ◽  
Antibody Response ◽  
Symptom Onset ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Virus Neutralization ◽  
The Face ◽  
Delta Virus

Omicron has been shown to be highly transmissible and have extensive evasion of neutralizing antibody immunity elicited by vaccination and previous SARS-CoV-2 infection. Omicron infections are rapidly expanding worldwide often in the face of high levels of Delta infections. Here we characterized developing immunity to Omicron and investigated whether neutralizing immunity elicited by Omicron also enhances neutralizing immunity of the Delta variant. We enrolled both previously vaccinated and unvaccinated individuals who were infected with SARS-CoV-2 in the Omicron infection wave in South Africa soon after symptom onset. We then measured their ability to neutralize both Omicron and Delta virus at enrollment versus a median of 14 days after enrollment. Neutralization of Omicron increased 14-fold over this time, showing a developing antibody response to the variant. Importantly, there was an enhancement of Delta virus neutralization, which increased 4.4-fold. The increase in Delta variant neutralization in individuals infected with Omicron may result in decreased ability of Delta to re-infect those individuals. Along with emerging data indicating that Omicron, at this time in the pandemic, is less pathogenic than Delta, such an outcome may have positive implications in terms of decreasing the Covid-19 burden of severe disease.

scholarly journals SARS-CoV-2 Omicron has extensive but incomplete escape of Pfizer BNT162b2 elicited neutralization and requires ACE2 for infection

2021 ◽  
Author(s):  
Sandile Cele ◽  
Laurelle Jackson ◽  
Khadija Khan ◽  
David S Khoury ◽  
Thandeka Moyo-Gwete ◽  
...  
Keyword(s):  
South Africa ◽  
Geometric Mean ◽  
Severe Disease ◽  
Neutralization Assay ◽  
Virus Neutralization ◽  
Dependent Manner ◽  
Focus Formation ◽  
Live Virus ◽  
Virus Neutralization Assay ◽  
Previous Infection

The emergence of the Omicron variant (1) of SARS-CoV-2 in November 2021 in South Africa has raised concerns that, based on the large number of mutations in the spike protein and elsewhere on the virus (https://covdb.stanford.edu/page/mutation-viewer/#sec_b-1-351), this variant will have considerable escape from vaccine elicited immunity. Furthermore, several mutations in the receptor binding domain and S2 are predicted to impact transmissibility and affinity for ACE-2. Here we investigated whether Omicron escapes antibody neutralization elicited by the Pfizer BNT162b2 mRNA vaccine and whether the virus still requires binding to the ACE2 receptor to infect cells. We used an early passage of isolated and sequence confirmed live Omicron virus isolated in South Africa. We used a human lung cell line clone (H1299-ACE2) engineered to express the ACE2 receptor (2) to both isolate the virus and test neutralization. We also tested growth in the parental H1299 which do not overexpress ACE2 and are not appreciably infectable with SARS-CoV-2 (Fig S1). The H1299-ACE2 cells were similar to Vero-E6 in titer dependent focus formation, but were considerably more sensitive (Fig S2). We observed that Omicron infected the ACE2-expressing cells in a concentration dependent manner but did not infect the parental H1299 cells, indicating that ACE2 is required for Omicron entry (Fig. 1A). We then tested the ability of plasma from BNT162b2 vaccinated study participants to neutralize Omicron versus ancestral D614G virus in a live virus neutralization assay. We tested 14 plasma samples from 12 participants (Table S1), with 6 having no previous record of SARS-CoV-2 infection nor detectable nucleocapsid antibodies indicative of previous infection. For two of these participants, we used samples from two timepoints. The remaining 6 participants had a record of previous infection in the first SARS-CoV-2 infection wave in South Africa where infection was with ancestral D614G virus (Table S1). Geometric mean titer (GMT) FRNT50 (inverse of the plasma dilution required for 50% reduction in infection foci number) was 1321 for D614G. These samples therefore had very strong neutralization of D614G virus, consistent with sampling soon after vaccination. GMT FRNT50 for the same samples was 32 for Omicron, a 41-fold decline (Fig 1B). However, the escape was incomplete, with 5 of the participants, all previously infected, showing relatively high neutralization titers with Omicron. Beta variant escape from BNT162b2 in a live virus neutralization assay has been reported to be substantial (3) and our own data confirmed these results (4), with about 3-fold reduction in FRNT50. The results we present here with Omicron show much more extensive escape. However, escape was incomplete in participants with higher FRNT50 due to previous infection. Previous infection, followed by vaccination or booster is likely to increase the neutralization level and likely confer protection from severe disease in Omicron infection.

scholarly journals SARS-CoV-2 vaccination induces neutralizing antibodies against pandemic and pre-emergent SARS-related coronaviruses in monkeys

2021 ◽  
Author(s):  
Kevin O. Saunders ◽  
Esther Lee ◽  
Robert Parks ◽  
David R. Martinez ◽  
Dapeng Li ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Receptor Binding Domain ◽  
Neutralization Titer ◽  
The Uk ◽  
Further Development

SUMMARYBetacoronaviruses (betaCoVs) caused the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, and now the SARS-CoV-2 pandemic. Vaccines that elicit protective immune responses against SARS-CoV-2 and betaCoVs circulating in animals have the potential to prevent future betaCoV pandemics. Here, we show that immunization of macaques with a multimeric SARS-CoV-2 receptor binding domain (RBD) nanoparticle adjuvanted with 3M-052-Alum elicited cross-neutralizing antibody responses against SARS-CoV-1, SARS-CoV-2, batCoVs and the UK B.1.1.7 SARS-CoV-2 mutant virus. Nanoparticle vaccination resulted in a SARS-CoV-2 reciprocal geometric mean neutralization titer of 47,216, and robust protection against SARS-CoV-2 in macaque upper and lower respiratory tracts. Importantly, nucleoside-modified mRNA encoding a stabilized transmembrane spike or monomeric RBD protein also induced SARS-CoV-1 and batCoV cross-neutralizing antibodies, albeit at lower titers. These results demonstrate current mRNA vaccines may provide some protection from future zoonotic betaCoV outbreaks, and provide a platform for further development of pan-betaCoV nanoparticle vaccines.

scholarly journals The kinetic variations of anti-nucleocapsid antibody in SARS-CoV-2 infection

2021 ◽  
Author(s):  
Shoji Kawada ◽  
Atsushi Ogata ◽  
Yasuhiro Kato ◽  
Masashi Okamoto ◽  
Yuta Yamaguchi ◽  
...  
Keyword(s):  
Immune Response ◽  
Severe Acute Respiratory Syndrome ◽  
Antibody Response ◽  
Nucleocapsid Protein ◽  
Healthcare Workers ◽  
Humoral Immune ◽  
Antibody Persistence ◽  
Decay Pattern ◽  
Kinetics Of

AbstractThe humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a pivotal role in controlling coronavirus disease 2019 (COVID-19) infections. However, little is known about the persistence of the antibody response.We evaluated that the kinetics of anti-nucleocapsid protein antibody of SARS-CoV2 infected healthcare workers in COVID-19 cluster occurred hospital. The long-term kinetics of anti-N antibody was classified high and keep pattern, high and decay pattern, and low and keep pattern. COVID-19 contact and symptomaticity was not related to kinetic patterns.The reason of kinetic difference was still unclear. However natural anti-SARS-CoV-2 antibody persistence was not uniform, suggesting inter-individual difference of SARS-CoV2 vaccine efficacy.

scholarly journals Rectal Immunization with Rotavirus Virus-Like Particles Induces Systemic and Mucosal Humoral Immune Responses and Protects Mice against Rotavirus Infection

2006 ◽  
Vol 80 (4) ◽  
pp. 1752-1761 ◽  
Author(s):  
Nathalie Parez ◽  
Cynthia Fourgeux ◽  
Ali Mohamed ◽  
Catherine Dubuquoy ◽  
Mathieu Pillot ◽  
...  
Keyword(s):  
Antibody Response ◽  
Immunoglobulin A ◽  
Virus Shedding ◽  
Virus Like Particles ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Immunization Strategies ◽  
Rectal Route ◽  
Rectal Delivery ◽  
Fecal Virus

ABSTRACT To evaluate whether the rectal route of immunization may be used to provide appropriate protection against enteric pathogens such as rotaviruses (RV), we studied the antibody response and the protection induced by rectal immunization of mice with RV virus-like particles (VLP). For this purpose, 6-week-old BALBc mice were rectally immunized twice with RV 8-2/6/7-VLP derived from the bovine RV RF81 strain either alone or combined with various adjuvants including four toxins [cholera toxin (CT) and three attenuated Escherichia coli-derived heat-labile toxins (LTs), LT(R192G), LT(R72), and LT(K63)] and two Toll-like receptor-targeting adjuvants (CpG and resiquimod). Six weeks after the second immunization, mice were challenged with murine RV strain ECw. RV VLP administered alone were not immunogenic and did not protect mice against RV challenge. By contrast, RV VLP combined with any of the toxin adjuvants were immunogenic (mice developed significant titers of anti-RV immunoglobulin A [IgA] in both serum and feces and of anti-RV IgG in serum) and either efficiently induced complete protection of the mice (no detectable fecal virus shedding) or, for LT(K63), reduced the amount of fecal virus shedding after RV challenge. When combined with RV VLP, CpG and resiquimod failed to achieve protection, although CpG efficiently induced an antibody response to RV. These results support the consideration of the rectal route for the development of new immunization strategies against RV infection. Rectal delivery of a VLP-based vaccine might allow the use of adjuvants less toxic than, but as efficient as, CT.

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