A novel assessment method for COVID-19 humoral immunity duration using serial measurements in naturally-infected and vaccinated subjects.

Background: It is crucial for medical decision-making and vaccination strategies to collect information on sustainability of immune responses after infection or vaccination, and how long-lasting antibodies against SARS-COV-2 could provide a humoral and protective immunity, preventing reinfection with SARS-CoV-2 or its variants. The aim of this study is to present a novel method to quantitatively measure and monitor the diversity of SARS-CoV-2 specific antibody profiles over time. Methods: Two collections of serum samples were used in this study: A collection from 20 naturally-infected subjects (follow-ups to 1 year) and a collection from 83 subjects vaccinated with one or two doses of Pfizer BioNtech vaccine (BNT162b2/BNT162b2) (follow-ups to 6 months). The Multi-SARS-CoV-2 assay, a multiparameter serology test, developed for the serological confirmation of past-infections was used to determine the reactivity of six different SARS-CoV-2 antigens. For each patient sample, 3 dilutions (1/50, 1/400 and 1/3200) were defined as an optimal set over the six antigens and their respective linear ranges, allowing accurate quantitation of the corresponding six specific antibodies. Nonlinear mixed-effects modelling was applied to convert intensity readings from 3 determined dilutions to a single quantification value for each antibody. Results: Median half-life for the 20 naturally infected vs 74 vaccinated subjects (two doses) was respectively 120 vs 50 days for RBD, 127 vs 53 days for S1 and 187 vs 86 days for S2 antibodies. Respectively, 90% of the antibody concentration wanes after 158 vs 398 days for RBD, 171 vs 420 days for S1, and 225 vs 620 days for S2 after the second vaccine shot. Conclusion: The newly proposed method, based on a series of a limited number of dilutions, can convert a conventional qualitative assay into a quantitative assay. This conversion helps define the sustainability of specific immune responses against each relevant viral antigen and can help in defining the protection characteristics after an infection or a vaccination.

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Vaccination strategy and anti - SARS-CoV-2 S titers in healthcare workers of the INT – IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy)

Infectious Agents and Cancer ◽

10.1186/s13027-021-00375-2 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Ernesta Cavalcanti ◽

Maria Antonietta Isgrò ◽

Domenica Rea ◽

Lucia Di Capua ◽

Giusy Trillò ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Healthcare Workers ◽

Geometric Mean ◽

Vaccination Strategy ◽

Antibody Responses ◽

Cancer Center ◽

Serum Samples ◽

Humoral Immune ◽

History Of

Abstract Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of people globally, requiring the development of billions of different vaccine doses. The SARS-CoV-2 spike mRNA vaccine (named BNT162b2/Pfizer), authorized by the FDA, has shown high efficacy in preventing SARS-CoV-2 infection after administration of two doses in individuals 16 years of age and older. In the present study, we retrospectively evaluated the differences in the SARS-CoV-2 humoral immune response after vaccine administration in the two different cohorts of workers at the INT - IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy): previously infected to SARS-CoV-2 subjects and not infected to SARS-CoV-2 subjects. Methods We determined specific anti-RBD (receptor-binding domain) titers against trimeric spike glycoprotein (S) of SARS-CoV-2 by Roche Elecsys Anti-SARS-CoV-2 S immunoassay in serum samples of 35 healthcare workers with a previous documented history of SARS-CoV-2 infection and 158 healthcare workers without, after 1 and 2 doses of vaccine, respectively. Moreover, geometric mean titers and relative fold changes (FC) were calculated. Results Both previously infected and not infected to SARS-CoV-2 subjects developed significant immune responses to SARS-CoV-2 after the administration of 1 and 2 doses of vaccine, respectively. Anti-S antibody responses to the first dose of vaccine were significantly higher in previously SARS-CoV-2-infected subjects in comparison to titers of not infected subjects after the first as well as the second dose of vaccine. Fold changes for subjects previously infected to SARS-CoV-2 was very modest, given the high basal antibody titer, as well as the upper limit of 2500.0 BAU/mL imposed by the Roche methods. Conversely, for naïve subjects, mean fold change following the first dose was low ($$ \overline{x} $$ x ¯ =1.6), reaching 3.8 FC in 72 subjects (45.6%) following the second dose. Conclusions The results showed that, as early as the first dose, SARS-CoV-2-infected individuals developed a remarkable and statistically significant immune response in comparison to those who did not contract the virus previously, suggesting the possibility of administering only one dose in previously SARS-CoV-2-infected subjects. FC for previously infected subjects should not be taken into account for the generally high pre-vaccination values. Conversely, FC for not infected subjects, after the second dose, were = 3.8 in > 45.0% of vaccinees, and ≤ 3.1 in 19.0%, the latter showing a potential susceptibility to further SARS-CoV-2 infection.

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Brucella abortus RB51 and Hot Saline Extract from Brucella ovis as Antigens in a Complement Fixation Test Used To Detect Sheep Vaccinated with Brucella abortus RB51

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.8.1.119-122.2001 ◽

2001 ◽

Vol 8 (1) ◽

pp. 119-122 ◽

Cited By ~ 5

Author(s):

Rosanna Adone ◽

Franco Ciuchini

Keyword(s):

Immune Responses ◽

Brucella Abortus ◽

Complement Fixation Test ◽

Complement Fixation ◽

Infected Sheep ◽

Fixation Test ◽

Anticomplementary Activity ◽

Serum Samples ◽

Saline Extract ◽

Brucella Ovis

ABSTRACT The efficacy of Brucella abortus RB51 and hot saline extract (HSE) from Brucella ovis as antigens in complement fixation (CF) tests was comparatively evaluated in detecting immune responses of sheep vaccinated with B. abortus strain RB51. For this study, four 5-month-old sheep were vaccinated subcutaneously with 5 × 109 CFU of RB51, and two sheep received saline. Serum samples collected at different times after vaccination were tested for the presence of antibodies to RB51 by a CF test with RB51 as antigen, previously deprived of anticomplementary activity, and with HSE antigen, which already used as the official antigen to detectB. ovis-infected sheep. The results showed that vaccinated sheep developed antibodies which reacted weakly against HSE antigen and these antibodies were detectable for 30 days after vaccination. However, antibodies to RB51 could be detected for a longer period after vaccination by using homologous RB51 antigen in CF tests. In fact, high titers were still present at 110 days postvaccination with RB51 antigen. Sera from sheep naturally infected with B. ovisalso reacted to RB51 but gave lower titers than those detected by HSE antigen. As expected, all sera from RB51-vaccinated sheep remained negative when tested with standard S-type Brucella standard antigens.

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Immune responses of Texel sheep to excretory/secretory products of adult Haemonchus contortus

Parasitology ◽

10.1017/s0031182000076198 ◽

1994 ◽

Vol 108 (3) ◽

pp. 351-357 ◽

Cited By ~ 61

Author(s):

H. D. F. H. Schallig ◽

M. A. W. van Leeuwen ◽

W. M. L. Hendrikx

Keyword(s):

Immune Response ◽

Immune Responses ◽

Haemonchus Contortus ◽

Lymphocyte Proliferation ◽

The Other ◽

Proliferation Index ◽

Serum Samples ◽

Immunoblotting Analysis ◽

Molecular Weights ◽

Secretory Products

SUMMARYThe excretory/secretory (E/S) products of adult Haemonchus contortus comprise of at least 15 polypeptides with molecular weights ranging from 10 to > 100 kDa. These E/S products induce an immune response in infected Texel sheep, as demonstrated by specific IgGI levels and a significant lymphocyte proliferation index. Moreover, immunoblotting analysis revealed that sera of primary H. contortus-infected sheep specifically recognize a 24 kDa E/S product. In addition, sera of challenged sheep react strongly with a 15 kDa E/S product. The other E/S products of H. contortus showed immunoreactivity with serum samples of Haemonchus-infected sheep as well as with samples of sheep harbouring other trichostrongylid infections. These cross-reacting epitopes are the main cause of the lack of specificity of an E/S material- based ELISA. This ELISA can differentiate Haemonchus infections from Nematodirus battus infections, but not from Ostertagia circumcincta or Trichostrongylus colubriformis infections.

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Influenza Anti-Stalk Antibodies: Development of a New Method for the Evaluation of the Immune Responses to Universal Vaccine

Vaccines ◽

10.3390/vaccines8010043 ◽

2020 ◽

Vol 8 (1) ◽

pp. 43 ◽

Cited By ~ 3

Author(s):

Alessandro Manenti ◽

Agnieszka Katarzyna Maciola ◽

Claudia Maria Trombetta ◽

Otfried Kistner ◽

Elisa Casa ◽

...

Keyword(s):

Immune Responses ◽

Competitive Elisa ◽

Influenza Vaccines ◽

Elisa Method ◽

Serum Samples ◽

Universal Vaccine ◽

Administration Routes ◽

Hemagglutinin Protein ◽

Protective Antibodies ◽

Universal Influenza Vaccine

Growing interest in universal influenza vaccines and novel administration routes has led to the development of alternative serological assays that are able to detect antibodies against conserved epitopes. We present a competitive ELISA method that is able to accurately determine the ratio of serum immunoglobulin G directed against the different domains of the hemagglutinin, the head and the stalk. Human serum samples were treated with two variants of the hemagglutinin protein from the A/California/7/2009 influenza virus. The signals detected were assigned to different groups of antibodies and presented as a ratio between head and stalk domains. A subset of selected sera was also tested by hemagglutination inhibition, single radial hemolysis, microneutralization, and enzyme-linked lectin assays. Pre-vaccination samples from adults showed a quite high presence of anti-stalk antibodies, and the results were substantially in line with those of the classical serological assays. By contrast, pre-vaccination samples from children did not present anti-stalk antibodies, and the majority of the anti-hemagglutinin antibodies that were detected after vaccination were directed against the head domain. The presented approach, when supported by further assays, can be used to assess the presence of specific anti-stalk antibodies and the potential boost of broadly protective antibodies, especially in the case of novel universal influenza vaccine approaches.

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Modelling upper respiratory viral load dynamics of SARS-CoV-2

BMC Medicine ◽

10.1186/s12916-021-02220-0 ◽

2022 ◽

Vol 20 (1) ◽

Author(s):

Joseph D. Challenger ◽

Cher Y. Foo ◽

Yue Wu ◽

Ada W. C. Yan ◽

Mahdi Moradi Marjaneh ◽

...

Keyword(s):

Viral Load ◽

Immune Responses ◽

Mechanistic Model ◽

Severity Of Illness ◽

Upper Respiratory Tract ◽

Neutralising Antibodies ◽

Immune Mediated ◽

Peak Viral Load ◽

Upper Respiratory ◽

Serial Measurements

AbstractRelationships between viral load, severity of illness, and transmissibility of virus are fundamental to understanding pathogenesis and devising better therapeutic and prevention strategies for COVID-19. Here we present within-host modelling of viral load dynamics observed in the upper respiratory tract (URT), drawing upon 2172 serial measurements from 605 subjects, collected from 17 different studies. We developed a mechanistic model to describe viral load dynamics and host response and contrast this with simpler mixed-effects regression analysis of peak viral load and its subsequent decline. We observed wide variation in URT viral load between individuals, over 5 orders of magnitude, at any given point in time since symptom onset. This variation was not explained by age, sex, or severity of illness, and these variables were not associated with the modelled early or late phases of immune-mediated control of viral load. We explored the application of the mechanistic model to identify measured immune responses associated with the control of the viral load. Neutralising antibodies correlated strongly with modelled immune-mediated control of viral load amongst subjects who produced neutralising antibodies. Our models can be used to identify host and viral factors which control URT viral load dynamics, informing future treatment and transmission blocking interventions.

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Predictive value of anti-cell and anti-human immunodeficiency virus (HIV) humoral responses in HIV-1-exposed seronegative cohorts of European and Asian origin

Journal of General Virology ◽

10.1099/vir.0.80585-0 ◽

2005 ◽

Vol 86 (2) ◽

pp. 339-348 ◽

Cited By ~ 29

Author(s):

L. Lopalco ◽

C. Barassi ◽

C. Paolucci ◽

D. Breda ◽

D. Brunelli ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Immune Responses ◽

Serum Samples ◽

Predictive Values ◽

Asian Populations ◽

Immunodeficiency Virus ◽

Hiv Exposure ◽

Route Of Exposure ◽

Humoral Responses ◽

Hiv 1

Unconventional immune responses have been demonstrated in individuals who, despite repeated exposure to human immunodeficiency virus (HIV) infection, remain seronegative. As environmental exposure to pathogens and genetic background may modulate immune responses differentially, one Italian and two Asian populations of HIV-1-exposed seronegative individuals were studied. In serum samples from each group, IgG to CCR5, IgG to CD4 and IgA to gp41 were measured, which were previously described as markers of unconventional immunity in HIV-exposed seronegative Caucasians. Given the importance of conformational epitopes in virus–cell interactions, IgG to CD4–gp120 complex was also measured. It was found that markers of HIV exposure were present in all populations studied. HIV-specific humoral responses (IgA to gp41 and IgG to CD4–gp120 complex) were extremely significant predictors of HIV exposure (P<0·0001 in both cases), whereas the predictive values of anti-cell antibodies (anti-CCR5 and anti-CD4) varied between populations. Evidence is provided for the correlation of these differences with route of exposure to HIV and level of natural antibodies to cross-reactive microbial antigens. In conclusion, exposed seronegative individuals of ethnically different origins display similar signs of HIV-dependent unconventional immunity. A specific relevance must be attributed to different innate and acquired factors.

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Impaired Humoral Response to Vaccines among HIV-Exposed Uninfected Infants

Clinical and Vaccine Immunology ◽

10.1128/cvi.05065-11 ◽

2011 ◽

Vol 18 (9) ◽

pp. 1406-1409 ◽

Cited By ~ 44

Author(s):

Beatriz Mariana Abramczuk ◽

Taís Nitsch Mazzola ◽

Yara Maria Franco Moreno ◽

Tatiane Queiroz Zorzeto ◽

Wagner Quintilio ◽

...

Keyword(s):

Hepatitis B ◽

Immune Responses ◽

Neutralizing Antibodies ◽

Geometric Mean ◽

Humoral Response ◽

Vaccine Response ◽

Serum Samples ◽

Hiv Exposed ◽

Exposed Uninfected

ABSTRACTLittle is known about the vaccine protective response for infants born from HIV-infected mothers. We evaluated the antibody response to hepatitis B, tetanus, and diphtheria vaccine in vertically HIV-exposed uninfected infants and compared them to those of control infants not exposed to the virus. The quantitative determination of specific neutralizing antibodies against hepatitis B, diphtheria, and tetanus were performed blindly on serum samples. The results showed that 6.7% of the HIV-exposed uninfected individuals were nonresponders to hepatitis B vaccine (anti-HBs titer, <10 mIU/ml), and 64.4% were very good responders (anti-HBs titer, ≥1,000 mIU/ml), whereas only 3.6% of the nonexposed infants were nonresponders (χ2=10.93; 1 df). The HIV-exposed uninfected infants showed protective titers for diphtheria and tetanus but lower geometric mean anti-tetanus titers compared to those of the HIV-unexposed infants. Our data point to the necessity of evaluating vaccine immune responses in these children and reinforced that alterations in lymphocyte numbers and functions reported for newborns from HIV-infected mothers interfere with the vaccine response.

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A Novel Method to Assess Safety of Buried Pressure Pipelines under Non-Random Process Seismic Excitation based on Cloud Model

Applied Sciences ◽

10.3390/app9040812 ◽

2019 ◽

Vol 9 (4) ◽

pp. 812 ◽

Cited By ~ 2

Author(s):

Peng Zhang ◽

Yihuan Wang ◽

Guojin Qin

Keyword(s):

Random Process ◽

Earthquake Engineering ◽

Random Vibration ◽

Cloud Model ◽

Quantitative Description ◽

Assessment Method ◽

Small Sample ◽

Seismic Excitation ◽

Convex Model ◽

Novel Method

It is necessary to conduct a safety assessment for pipelines which are regarded as important lifeline projects after an earthquake. Since the random process of loading in earthquake engineering requires a large amount of samples, this paper establishes a non-random vibration method based on convex model theory and applies it to small sample engineering. Moreover, a space–time analytical model of buried pipeline and a finite element model are established to solve the dynamic response of pipelines with non-random process seismic excitation. Furthermore, the randomness of the stress values of the pipeline subjected to earthquake and the fuzziness of the degree of damage to pipelines are considered. Therefore, a novel method for assessing damage to pipelines is proposed based on cloud model. The results indicate that an analysis of non-random vibration combined with the cloud inference method can solve the fuzziness and randomness of the quantitative description and qualitative concept conversion for damage evaluation of pipelines. The method is also an adaptive and effective assessment method for pipelines exposed to earthquake and is able to promote safety management of pipeline engineering.

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Study of Neuraminidase-Inhibiting Antibodies in Clinical Trials of Live Influenza Vaccines

Antibodies ◽

10.3390/antib9020020 ◽

2020 ◽

Vol 9 (2) ◽

pp. 20

Author(s):

Yulia Desheva ◽

Tatiana Smolonogina ◽

Svetlana Donina ◽

Larisa Rudenko

Keyword(s):

Immune Response ◽

Clinical Trials ◽

Immune Responses ◽

Influenza Infection ◽

H1n1 Influenza ◽

Antibody Responses ◽

Influenza Vaccines ◽

Statistical Relationship ◽

Serum Samples ◽

H5n1 Influenza

Background: Currently, the immunogenicity of influenza vaccines is assessed by detecting an increase of hemagglutination inhibition (HI) antibodies. As neuraminidase (NA)-based immunity may be significant in protecting against influenza infection, detection of neuraminidase inhibiting (NI) antibodies may improve the assessment of the immunogenicity of influenza vaccines. Methods: We investigated the immune response to NA in people after immunization with live influenza vaccines (LAIVs). A number of A/H7NX or A/H6NX viruses were used to detect NI antibodies, using an enzyme-linked lectin assay (ELLA). Results: Seasonal LAIV immunization stimulated an increase in NI antibodies not only to homologous A/H1N1 influenza, but also to A/H1N1pdm09 and A/H5N1 influenza. After A/17/California/09/38 (H1N1) pdm09 LAIV vaccination, there was no statistical relationship between post-vaccinated antibody seroconversion and two surface glycoproteins in serum samples obtained from the same individuals (p = 0.24). Vaccination with LAIV of H5N2, H2N2, H7N3, and H7N9 subtypes led to 7%–29.6% NI antibody seroconversions in the absence of HI antibody conversions. There was relatively low coordination of hemagglutinin (HA) and NA antibody responses (r = 0.24–0.59). Conclusions: The previously noted autonomy for HI and NI immune responses was confirmed when assessing the immunogenicity of LAIVs. Combining the traditional HI test with the detection of NI antibodies can provide a more complete assessment of LAIV immunogenicity.

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Analytical and clinical performance of a homogeneous enzymatic LDL-cholesterol assay compared with the ultracentrifugation-dextran sulfate-Mg2+ method

Clinical Chemistry ◽

10.1093/clinchem/44.6.1242 ◽

1998 ◽

Vol 44 (6) ◽

pp. 1242-1250 ◽

Cited By ~ 71

Author(s):

Nader Rifai ◽

Elizabeth Iannotti ◽

Kristen DeAngelis ◽

Terence Law

Keyword(s):

Dextran Sulfate ◽

Ldl Cholesterol ◽

Clinical Performance ◽

Total Error ◽

Analytical Performance ◽

Medical Decision ◽

Serum Samples ◽

Predictive Values ◽

Clinical Laboratories ◽

Wide Range

Abstract LDL-cholesterol (LDL-C) concentration is currently determined in most clinical laboratories by the Friedewald calculation. This approach has several limitations and may not meet the current total error requirement in LDL-C measurement of ≤ 12%. We evaluated the analytical and clinical performance of the direct N-geneous LDL-C assay (Equal Diagnostics). The N-geneous method correlated highly with the modified beta-quantification assay (r = 0.95; y = 0.91x + 70.6 mg/L; n = 199), showed no significant effect of increased triglyceride or other common interferants, and performed adequately in serum samples from nonfasting individuals. This assay demonstrated a mean total error of 6.75% over a wide range of LDL-C concentrations. In addition, at the medical decision cutoff points, this LDL-C assay showed positive predictive values of 78–95% and negative predictive values of 84–99%. We conclude that the N-geneous LDL-C meets the currently established analytical performance goals and appears to have a role in the diagnosis and management of hypercholesterolemic patients.

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