583. SARS-CoV-2 Spike Protein S1/S2 Antibodies after Vaccination with Sinopharm in Peruvian Physicians

Abstract Background Peru started its national vaccination campaign in February 2021 using Sinopharm vaccine, targeting healthcare personnel on its initial phase. Although the immunogenicity of this vaccine was tested in clinical trials, there are no studies that evaluated the humoral response post vaccination in Peru. Methods We conducted a cross sectional study, which objective was to evaluate the humoral immunogenicity triggered by the Sinopharm vaccine in Peruvian physicians. We collected demographic and epidemiologic data via an electronic. The SARS-CoV-2 spike protein S1/S2 antibodies were measured by chemiluminescense (Liaison®). A positive test was defined as >15 U/ml, which has correlation of 95% with neutralizing antibodies measured by plaque reduction neutralizing test. Results 92 participants were enrolled in the study. The epidemiologic characteristics are described in table 1. The mean level of antibodies measured at least 2 weeks from the second vaccine dose was 67.5 ± 70.5 U/ml. 85.7% of the study cohort had positive S1/S2 antibodies. In the univariate analysis, an imperfect negative correlation was found between the level of antibodies and participants’ age (r= -0.24; regression F test 5.25; p = 0.0242). A weak negative correlation was observed between the antibody titer and the time elapsed from the second vaccine dose and the day of antibody measurement (r= -0.17). A higher antibody level post vaccine was found in individuals who worked in COVID units (105.5 U / mL vs 58.2 U / mL; p = 0.0125), and in participants with history of COVID (216.5 U / mL vs 81.2 U / mL; p = < 0.0000). Hypertension was associated with lower antibody titers (36.9 U / mL vs. 74.6; p = 0.0464). In the multivariate analysis, working in COVID units, having previous COVID infection and shorter time from second vaccine dose and day of antibody measurement were associated with higher antibody levels post vaccine (table 2). Conclusion Our study showed that the time elapsed from the second vaccine dose and the day of antibody measurement, having previous COVID-19 infection and working in COVID -19 units may help to predict higher antibody titers post vaccine. Larger studies to evaluate the humoral response post Sinopharm vaccine and its clinical implications are still needed in Peru. Disclosures All Authors: No reported disclosures

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The Kinetics of Humoral Response and its Relationship with the Disease Severity in COVID-19

10.21203/rs.3.rs-35381/v1 ◽

2020 ◽

Author(s):

Lili Ren ◽

Lulu Zhang ◽

De Chang ◽

Li Guo ◽

Junwen Wang ◽

...

Keyword(s):

Disease Severity ◽

Neutralizing Antibodies ◽

Late Onset ◽

Humoral Response ◽

Spike Protein ◽

Appearance Time ◽

Global Pandemic ◽

Antibody Titers ◽

Kinetics Of

Abstract Coronavirus Disease 2019 (COVID-19) has caused global pandemic. Here we profiled the humoral response against SARS-CoV-2 by measuring immunoglobulin (Ig) A, IgM and IgG against nucleocapsid, spike proteins and IgM, IgG antibodies against receptor-binding domain (RBD) of the spike protein along with total neutralizing antibodies. We tested 279 plasma samples collected from 176 COVID-19 patients. We demonstrate more severe cases have a late onset in the humoral response compared to mild/moderate infections. All the antibody titers continue to rise in patients with COVID-19 over the disease course. However, these levels are mostly unrelated to the disease severity. The appearance time and titers of neutralizing antibodies showed significant positive correlation to the antibodies against spike protein. Our results suggest late onset of antibody response as a risk factor for disease severity, however there is a limited role of antibody titers in predicting disease severity of COVID-19.

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The kinetics of humoral response and its relationship with the disease severity in COVID-19

Communications Biology ◽

10.1038/s42003-020-01526-8 ◽

2020 ◽

Vol 3 (1) ◽

Cited By ~ 1

Author(s):

Lili Ren ◽

Lulu Zhang ◽

De Chang ◽

Junwen Wang ◽

Yongfeng Hu ◽

...

Keyword(s):

Disease Severity ◽

Neutralizing Antibodies ◽

Late Onset ◽

Geometric Mean ◽

Humoral Response ◽

Spike Protein ◽

Appearance Time ◽

Global Pandemic ◽

Antibody Titers

AbstractCoronavirus Disease 2019 (COVID-19) has caused a global pandemic. Here we profiled the humoral response against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by measuring immunoglobulin (Ig) A, IgM, and IgG against nucleocapsid and spike proteins, along with IgM and IgG antibodies against receptor-binding domain (RBD) of the spike protein and total neutralizing antibodies (NAbs). We tested 279 plasma samples collected from 176 COVID-19 patients who presented and enrolled at different stages of their disease. Plasma dilutions were optimized and based on the data, a single dilution of plasma was used. The mean absorbance at 450 nm was measured for Ig levels and NAbs were measured using geometric mean titers. We demonstrate that more severe cases have a late-onset in the humoral response compared to mild/moderate infections. All the antibody titers continue to rise in patients with COVID-19 over the disease course. However, these levels are mostly unrelated to disease severity. The appearance time and titers of NAbs showed a significant positive correlation to the antibodies against spike protein. Our results suggest the late onset of antibody response as a risk factor for disease severity, however, there is a limited role of antibody titers in predicting disease severity of COVID-19.

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Titers of Neutralizing Antibodies against SARS-CoV-2 Are Independent of Symptoms of Non-Severe COVID-19 in Young Adults

Viruses ◽

10.3390/v13020284 ◽

2021 ◽

Vol 13 (2) ◽

pp. 284

Author(s):

Hulda R. Jonsdottir ◽

Michel Bielecki ◽

Denise Siegrist ◽

Thomas W. Buehrer ◽

Roland Züst ◽

...

Keyword(s):

Young Adults ◽

Neutralizing Antibodies ◽

Severe Disease ◽

Humoral Response ◽

Neutralizing Antibody ◽

Neutralization Assay ◽

Asymptomatic Infection ◽

Homogeneous Population ◽

Humoral Immune ◽

Antibody Titers

Neutralizing antibodies are an important part of the humoral immune response to SARS-CoV-2. It is currently unclear to what extent such antibodies are produced after non-severe disease or asymptomatic infection. We studied a cluster of SARS-CoV-2 infections among a homogeneous population of 332 predominantly male Swiss soldiers and determined the neutralizing antibody response with a serum neutralization assay using a recombinant SARS-CoV-2-GFP. All patients with non-severe COVID-19 showed a swift humoral response within two weeks after the onset of symptoms, which remained stable for the duration of the study. One month after the outbreak, titers in COVID-19 convalescents did not differ from the titers of asymptomatically infected individuals. Furthermore, symptoms of COVID-19 did not correlate with neutralizing antibody titers. Therefore, we conclude that asymptomatic infection can induce the same humoral immunity as non-severe COVID-19 in young adults.

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Serological response to rabies virus induced by commercial vaccines in cattle

Ciência Rural ◽

10.1590/0103-8478cr20161044 ◽

2017 ◽

Vol 47 (10) ◽

Author(s):

Mathias Martins ◽

João Motta de Quadros ◽

Eduardo Furtado Flores ◽

Rudi Weiblen

Keyword(s):

Rabies Virus ◽

Neutralizing Antibodies ◽

Vaccine Dose ◽

Booster Vaccination ◽

Serological Response ◽

Serum Samples ◽

Anamnestic Response ◽

Post Vaccination ◽

Antibody Titers ◽

One Year

ABSTRACT: The antibody response to rabies virus (RABV) induced by commercial vaccines in heifers was investigated. For this, 84 heifers were vaccinated twice (30 days interval) with each of four vaccines (G1 = 14 animals; G2 = 24; G3 = 22 and G4 = 24) and received a booster vaccination 360 days later. Serum samples collected at different intervals after vaccination and 30 days after booster were submitted to a virus neutralizing (VN) assay for RABV antibodies. Thirty days after the second vaccine dose, 92% of the immunized animals presented VN titers ≥0.5UI/mL (geometric medium titers [GMT] 1.7 to 3.8UI/mL). At the day of the booster (360 days post-vaccination); however, the percentage of animals harboring antibody titers ≥0.5UI/mL had dropped to 31% (0-80% of the animals, depending on the vaccine), resulting in lower GMT (0.1 to 0.6UI/mL). Booster vaccination at day 360 resulted in a detectable anamnestic response in all groups, resulting in 83% of animals (65 to 100%) harboring VN titers ≥0.5UI/mL thirty days later (GMT 0.6 to 4.3UI/mL). These results indicated that these vaccines were able to induce an adequate anti-RABV response in all animals after prime vaccination (and after booster as well). However, the titers decreased, reaching titers <0.5UI/mL in approximately 70% of animals within the interval before the recommended booster. Thus, booster vaccination for rabies in cattle using the current vaccines should be performed before the recommended one-year interval, as to maintain neutralizing antibodies levels in most vaccinated animals.

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Durability of Response to a Third BNT162b2 Vaccine in Adults ≥60 Years

10.1101/2021.12.25.21268336 ◽

2021 ◽

Author(s):

Noa Eliakim Raz ◽

Amos Stemmer ◽

Yaara Leibovici-Weissman ◽

Asaf Ness ◽

Muhammad Awwad ◽

...

Keyword(s):

Adverse Events ◽

Neutralizing Antibodies ◽

Multivariable Analysis ◽

Vaccine Dose ◽

Neutralizing Antibody ◽

Clinical Frailty Scale ◽

Younger Adults ◽

The Third ◽

Antibody Titers ◽

Level 2

BACKGROUND Age and frailty are strong predictors of COVID-19 mortality. After the second BNT162b2 dose, immunity wanes faster in older (≥65 years) versus younger adults. The durability of response after the third vaccine is unclear. METHODS This prospective cohort study included healthcare workers/family members ≥60 years who received a third BNT162b2 dose. Blood samples were drawn immediately before (T0), 10-19 (T1), and 74-103 (T2) days after the third dose. Antispike IgG titers were determined using a commercial assay, seropositivity was defined as ≥50 AU/mL. Neutralizing antibody titers were determined at T2. Adverse events, COVID-19 infections, and clinical frailty scale (CFS) levels were documented. RESULTS The analysis included 97 participants (median age, 70 years [IQR, 66-74], 61% women, 58% CFS level 2). IgG titers, which increased significantly from T0 to T1 (medians, 440 AU/mL [IQR, 294-923] and 25,429 [14,203-36,114] AU/mL, respectively; P<0.001), decreased significantly by T2, but all remained seropositive (median, 8,306 AU/mL [IQR, 4595-14,701], P<0.001 vs T1). In a multivariable analysis, only time from the first vaccine was significantly associated with lower IgG levels at T2 (P=0.004). At T2, 60 patients were evaluated for neutralizing antibodies; all were seropositive (median, 1,294 antibody titer [IQR, 848-2,072]). Neutralizing antibody and antispike IgG levels were correlated (R=0.6, P<0.001). No major adverse events or COVID-19 infections were reported. CONCLUSIONS Antispike IgG and neutralizing antibodies levels remain adequate 3 months after the third BNT162b2 vaccine in healthy adults ≥60 years, although the decline in IgG is concerning. A third vaccine dose in this population should be top priority.

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Severe Acute Respiratory Syndrome-Associated Coronavirus Vaccines Formulated with Delta Inulin Adjuvants Provide Enhanced Protection while Ameliorating Lung Eosinophilic Immunopathology

Journal of Virology ◽

10.1128/jvi.02980-14 ◽

2014 ◽

Vol 89 (6) ◽

pp. 2995-3007 ◽

Cited By ~ 79

Author(s):

Yoshikazu Honda-Okubo ◽

Dale Barnard ◽

Chun Hao Ong ◽

Bi-Hung Peng ◽

Chien-Te Kent Tseng ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Neutralizing Antibodies ◽

Case Fatality ◽

Neutralizing Antibody ◽

The Elderly ◽

Spike Protein ◽

Interleukin 4 ◽

Unique Problem ◽

Antibody Titers ◽

Ifn Γ

ABSTRACTAlthough the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) epidemic was controlled by nonvaccine measures, coronaviruses remain a major threat to human health. The design of optimal coronavirus vaccines therefore remains a priority. Such vaccines present major challenges: coronavirus immunity often wanes rapidly, individuals needing to be protected include the elderly, and vaccines may exacerbate rather than prevent coronavirus lung immunopathology. To address these issues, we compared in a murine model a range of recombinant spike protein or inactivated whole-virus vaccine candidates alone or adjuvanted with either alum, CpG, or Advax, a new delta inulin-based polysaccharide adjuvant. While all vaccines protected against lethal infection, addition of adjuvant significantly increased serum neutralizing-antibody titers and reduced lung virus titers on day 3 postchallenge. Whereas unadjuvanted or alum-formulated vaccines were associated with significantly increased lung eosinophilic immunopathology on day 6 postchallenge, this was not seen in mice immunized with vaccines formulated with delta inulin adjuvant. Protection against eosinophilic immunopathology by vaccines containing delta inulin adjuvants correlated better with enhanced T-cell gamma interferon (IFN-γ) recall responses rather than reduced interleukin-4 (IL-4) responses, suggesting that immunopathology predominantly reflects an inadequate vaccine-induced Th1 response. This study highlights the critical importance for development of effective and safe coronavirus vaccines of selection of adjuvants based on the ability to induce durable IFN-γ responses.IMPORTANCECoronaviruses such as SARS-CoV and Middle East respiratory syndrome-associated coronavirus (MERS-CoV) cause high case fatality rates and remain major human public health threats, creating a need for effective vaccines. While coronavirus antigens that induce protective neutralizing antibodies have been identified, coronavirus vaccines present a unique problem in that immunized individuals when infected by virus can develop lung eosinophilic pathology, a problem that is further exacerbated by the formulation of SARS-CoV vaccines with alum adjuvants. This study shows that formulation of SARS-CoV spike protein or inactivated whole-virus vaccines with novel delta inulin-based polysaccharide adjuvants enhances neutralizing-antibody titers and protection against clinical disease but at the same time also protects against development of lung eosinophilic immunopathology. It also shows that immunity achieved with delta inulin adjuvants is long-lived, thereby overcoming the natural tendency for rapidly waning coronavirus immunity. Thus, delta inulin adjuvants may offer a unique ability to develop safer and more effective coronavirus vaccines.

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Should be a Third Dose of BNT162b2 mRNA COVID-19-Vaccine Administered in Patients with Myelofibrosis Under Ruxolitinib?

Blood ◽

10.1182/blood-2021-146381 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2573-2573

Author(s):

Giovanni Caocci ◽

Olga Mulas ◽

Daniela Mantovani ◽

Alessandro Costa ◽

Andrea Galizia ◽

...

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Present Report ◽

Univariate Analysis ◽

Vaccine Dose ◽

Humoral Response ◽

The Other ◽

World Health ◽

International Prognostic Scoring System ◽

Humoral Immune

Abstract Introduction. Patients with Myelofibrosis (MF) are considered fragile and thus eligible in Italy for COVID-19 BNT162b2 mRNA vaccination. According to the International Prognostic Scoring System (IPSS), patients with intermediate and high MF, may receive clinical benefits from ruxolitinib, the first approved JAK1/JAK2 inhibitor. Given the potent anti-inflammatory properties of ruxolitinib against immunocompetent cells, we previously reported a lower but non-statistically absolute IgG anti-Spike humoral response in vaccinated MF patients treated with ruxolitinib. In the present report we extended the cohort of MF patients. Methods. All MF patients received 2 injections of 30 ug per dose of BNT162b2 mRNA COVID-19 vaccine 3 weeks apart, according to the standard protocol. After injection, mild pain at the injection site was frequently reported. No serious adverse events were registered. The serum level of IgG anti-Spike glycoprotein was tested after a median time of 45 days (range 40-60) from the second vaccine dose, using the approved anti-SARS-CoV-2 IgG CLIA (LIAISON® SARS-CoV-2 TrimericS IgG assay, Diasorin, Saluggia, Italy). An Arbitrary Units per milliliter (AU/mL) ratio of <12.0 was considered to be negative, 12.0-15.0 AU/mL to be borderline and >15 AU/mL to be positive. A conversion of AU/mL to binding antibody units (BAU/mL) as recommended by the World Health Organization (WHO) guidelines was achieved considering the following equation: BAU/mL = 2.6*AU/mL. Results. Overall, 30 MF patients (median age 65 years, range 48-83) were vaccinated. A diagnosis of primary MF was reported in 21 cases (70%), post essential thrombocythemia-MF in 6 (20%) patients and post polycythemia vera-MF in 3 (10%) patients; 23 out of 30 patients (76.6%) were positive for the JAK2V617F, 5 (16.6%) for CALR mutation, 1 (3.3%) for MPL mutation and 1 patient (3.3%) resulted triple negative. Splenomegaly was observed in 14 patients (46%) and 19 (63.3%) reported comorbidities. Nineteen patients (63.3%) were classified as DIPSS low or intermediate-1 risk, and 11 (36.6%) as intermediate-2 or high risk. Fifteen patients (50%) were receiving ruxolitinib, at a median total dose of 20 mg/die (range 20-40 mg) and the remaining 15 patients other treatments (8 patients hydroxyurea and 7 only supportive therapy). None of the patients reported COVID-19 infection neither previous nor subsequently to vaccination. Overall, a positive immune response against COVID-19 was observed in 8 out of 15 patients (53.3%) in the ruxolitinib group, in comparison with 13 out 15 patients (86.6%) in the other treatment group (p=0,046). The absolute IgG anti-Spike value was lower in the ruxolitinib group (median 35.2±49.81) in comparison with the other group (median 226.1±163.9; p=<0.001), Figure 1. In univariate analysis, only ruxolitinib treatment was found associated with a lower humoral immune response to the vaccine. Conclusions. MF patients under ruxolitinib achieved a lower humoral immune response in comparison with MF patients who underwent other treatments. No COVID-19 infection was observed in both groups after vaccination, after a median follow up of 3 months since the second dose. Whether patients with a potential insufficient humoral response to vaccine will benefit from a third dose of BNT162b2 mRNA COVID-19 vaccine is a matter of further investigation. Our preliminary data need to be confirmed in larger cohort of MF patients. Figure 1 Figure 1. Disclosures Murru: Abbvie: Consultancy, Honoraria, Other: travel and accommodation; Janssen: Consultancy, Honoraria.

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Seroprevalence of SARS-CoV-2 IgG Antibodies After the Second BNT162b2 mRNA Vaccine in Japanese Kidney Transplant Recipients

10.21203/rs.3.rs-1120488/v1 ◽

2021 ◽

Author(s):

Tomoko Hamaya ◽

Shingo Hatakeyama ◽

Tohru Yoneyama ◽

Yuki Tobisawa ◽

Hirotake Kodama ◽

...

Keyword(s):

Mycophenolate Mofetil ◽

Kidney Transplant ◽

Neutralizing Antibodies ◽

Humoral Response ◽

Healthy Controls ◽

Transplant Recipients ◽

Igg Antibodies ◽

Kidney Transplant Recipients ◽

Univariate Logistic Regression Analysis ◽

Antibody Titers

Abstract We aimed to evaluate the rate of anti–SARS-CoV-2 IgG seropositivity and investigated factors associated with seropositivity after the second SARS-CoV-2 mRNA vaccination in kidney transplant (KT) recipients. This retrospective study conducted between June 2021 and November 2021 included 106 KT recipients and 127 healthy controls who received the second dose of the BNT162b2 mRNA vaccine at least seven days before the measurement of antibody titers. The titers of immunoglobulin G (IgG) antibodies against the receptor-binding domain of SARS-CoV-2 spike (S) protein were determined. Seropositivity was defined as an anti–SARS-CoV-2 IgG level of ≥15 units/mL, which was considered as the presence of sufficient neutralizing antibodies. The median ages and the seroprevalence rates of the healthy controls and KT recipients were 68 and 56 years and 98% and 22%, respectively. Univariate logistic regression analysis revealed that age >53 years, rituximab use, mycophenolate mofetil use, and KT vintage <7 years were negatively associated with anti–SARS-CoV-2 IgG seropositivity in KT recipients. Humoral response after the second BNT162b2 mRNA vaccine was greatly hindered by immunosuppression therapy in KT recipients. Older age, rituximab use, mycophenolate mofetil use, and KT vintage may play key roles in seroconversion.

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Function is more reliable than quantity to follow up the humoral response to the Receptor Binding Domain of SARS- CoV-2 Spike Protein after Natural Infection or COVID-19 vaccination

10.1101/2021.06.02.21257975 ◽

2021 ◽

Author(s):

Carlos A Sariol ◽

Petraleigh Pantoja ◽

Crisanta Serrano-Collazo ◽

Tiffant Rosa-Arocho ◽

Albersy Armina ◽

...

Keyword(s):

Immune Response ◽

Neutralizing Antibodies ◽

Natural Infection ◽

Vaccine Dose ◽

Humoral Response ◽

Neutralizing Antibody ◽

Viral Neutralization ◽

Neutralizing Activity ◽

Robust Immune Response

On this work we report that despite of a decline in the total anti-Spike antibodies the neutralizing antibodies remains at a similar level for an average of 98 days in a longitudinal cohort of 59 Hispanic/Latino exposed to SARS-CoV-2. We are also reporting that the percentage of neutralization correlates with the IgG titers and that in the first collected samples, IgG1 was the predominant isotype (62.71%), followed by IgG4 (15.25%), IgG3 (13.56%), and IgG2 (8.47%) during the tested period. The IgA was detectable in 28.81% of subjects. Only 62.71% of all subjects have detectable IgM in the first sample despite of confirmed infection by a molecular method. Our data suggests that 100% that seroconvert make detectable neutralizing antibody responses measured by a surrogate viral neutralization test. We also found that the IgG titers and neutralizing activity were higher after the first dose in 10 vaccinated subjects out of the 59 with prior infection compare to a subgroup of 21 subjects naive to SARS-CoV-2. One dose was enough but two were necessary to reach the maximum percentage of neutralization in subjects with previous natural infection or naive to SARS-CoV-2 respectively. Like the pattern seen after the natural infection, after the second vaccine dose, the total anti-S antibodies and titers declined but not the neutralizing activity which remains at same levels for more than 80 days after the first vaccine dose. That decline, however, was significantly lower in pre-exposed individuals which denotes the contribution of the natural infection priming a more robust immune response to the vaccine. Also, our data indicates that the natural infection induces a more robust humoral immune response than the first vaccine dose in unexposed subjects. However, the difference was significant only when the neutralization was measured but not by assessing the total anti-S antibodies or the IgG titers. This work is an important contribution to understand the natural immune response to the novel coronavirus in a population severely hit by the virus. Also provide an invaluable data by comparing the dynamic of the immune response after the natural infection vs. the vaccination and suggesting that a functional test is a better marker than the presence or not of antibodies. On this context our results are also highly relevant to consider standardizing methods that in addition to serve as a tool to follow up the immune response to the vaccines may also provide a correlate of protection.

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A single dose of replication-competent VSV-vectored vaccine expressing SARS-CoV-2 S1 protects against virus replication in a hamster model of severe COVID-19

10.1101/2021.01.29.428442 ◽

2021 ◽

Author(s):

Delphine C. Malherbe ◽

Drishya Kurup ◽

Christoph Wirblich ◽

Adam J. Ronk ◽

Chad Mire ◽

...

Keyword(s):

Animal Model ◽

Vesicular Stomatitis Virus ◽

Neutralizing Antibodies ◽

Specific Binding ◽

Vaccine Dose ◽

Spike Protein ◽

Hamster Model ◽

Rapid Control ◽

Vesicular Stomatitis ◽

Vectored Vaccine

SUMMARYThe development of effective countermeasures against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the agent responsible for the COVID-19 pandemic, is a priority. We designed and produced ConVac, a replication-competent vesicular stomatitis virus (VSV) vaccine vector that expresses the S1 subunit of SARS-CoV-2 spike protein. We used golden Syrian hamsters as animal model of severe COVID-19 to test the efficacy of the ConVac vaccine. A single vaccine dose elicited high levels of SARS-CoV-2 specific binding and neutralizing antibodies; following intranasal challenge with SARS-CoV-2, animals were protected from weight loss and viral replication in the lungs. No enhanced pathology was observed in vaccinated animals upon challenge, but some inflammation was still detected. The data indicate rapid control of SARS-CoV-2 replication by the S1-based VSV-vectored SARS-CoV-2 ConVac vaccine.

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