Serological Response to SARS-CoV-2 Messenger RNA Vaccine: Real-World Evidence from Italian Adult Population

Background: This study aims to investigate the extent of the BNT162b2 mRNA vaccine-induced antibodies against SARS-CoV-2 in a large cohort of Italian subjects belonging to the early vaccinated cohort in Italy. Methods: A prospective study was conducted between December 2020 and May 2021. Three blood samples were collected for each participant: one at the time of the first vaccine dose (T0), one at the time of the second vaccine dose, (T1) and the third 30 days after this last dose (T2). Results: We enrolled 2591 fully vaccinated subjects; 16.5% were frail subjects, and 9.8% were over 80 years old. Overall, 98.1% of subjects were seropositive when tested at T2, and 76.3% developed an anti-S IgG titer ≥4160 AU/mL, which is adequate to develop viral neutralizing antibodies. Seronegative subjects at T1 were more likely to remain seronegative at T2 or to develop a low–intermediate anti-S IgG titer (51–4159 AU/mL). Conclusions: In summary, vaccination leads to detectable anti-S IgG titer in nearly all vaccine recipients. Stratification of the seroconversion level could be useful to promptly identify high-risk groups who may not develop a viral neutralizing response, even in the presence of seroconversion, and therefore may remain at higher risk of infection, despite vaccination.

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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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Efficacy of a Third BNT162b2 mRNA COVID-19 Vaccine Dose in Patients with CLL who Failed Standard Two-dose Vaccination

Blood ◽

10.1182/blood.2021014085 ◽

2021 ◽

Author(s):

Yair Herishanu ◽

Galia Rahav ◽

Shai Levi ◽

Andrei Braester ◽

Gilad Itchaki ◽

...

Keyword(s):

Antibody Response ◽

Neutralizing Antibodies ◽

Response Rate ◽

Vaccine Dose ◽

Humoral Response ◽

Response Rates ◽

Lymphocytic Leukemia ◽

Vaccination Regimen ◽

The Third ◽

Anti Cd20

Patients with chronic lymphocytic leukemia (CLL) have an impaired antibody response to COVID-19 vaccination. Here, we evaluated the antibody response to a third BNT162b2 mRNA vaccine in patients with CLL/small lymphocytic lymphoma (SLL) who failed to achieve a humoral response after standard two-dose vaccination regimen. Anti-SARS-CoV-2S and neutralizing antibodies were measured 3 weeks after administration of the third dose. In 172 patients with CLL the antibody response rate was 23.8%. Response rate among actively treated patients (12.0%, n=12/100) was lower compared to treatment-naïve patients (40.0%, n=16/40; OR=4.9, 95% CI 1.9-12.9; p<0.001) and patients off-therapy (40.6%, n=13/32; OR=5.0, 95% CI 1.8-14.1; p<0.001), (p<0.001). In those actively treated with BTK inhibitors or venetoclax ± anti-CD20 antibody, response rates were extremely low (15.3%, n=9/59 and 7.7%, n=3/39, respectively). Only one of the 28 patients (3.6%) treated with anti-CD20 antibodies <12 months prior to vaccination responded. The anti-SARS-CoV-2S antibody levels correlated linearly with neutralizing antibody titers (r=0.732, p<0.001). In a multivariate analysis, the independent variables that were associated with response included lack of active therapy (OR=5.6, 95% CI 2.3-13.8; p<0.001) and serum IgA levels ≥80 mg/dL (OR=5.8, 95% CI 2.1-15.9; p<0.001) In conclusion, in patients with CLL/SLL who failed to achieve a humoral response after standard two-dose BNT162b2 mRNA vaccination regimen, close to a quarter responded to the third dose of vaccine. The antibody response rates were lower during active treatment and in patients with a recent exposure (<12 months prior to vaccination) to anti-CD20 therapy.

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Efficacy of the BNT162b2 mRNA COVID-19 Vaccine in Patients with Chronic Lymphocytic Leukemia: A Serologic and Cellular Study

Chemotherapy ◽

10.1159/000521229 ◽

2021 ◽

Author(s):

Stefano Molica ◽

Diana Giannarelli ◽

Mirella Lentini ◽

Daniela Zappala ◽

Ada Mannella ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Antibody Response ◽

Messenger Rna ◽

Vaccine Dose ◽

Lymphocytic Leukemia ◽

Serological Response ◽

Humoral Immune ◽

Treatment Naïve ◽

Cd20 Antibody ◽

Anti Cd20

Background: Antibody response following SARS-CoV2 vaccination is somewhat defective in chronic lymphocytic leukemia (CLL). Moreover, the correlation between serologic response and status of cellular immunity has been poorly studied. Objective: This study was undertaken to assess humoral immune and cellular responses to the BNT162b2 messenger RNA (mRNA) COVID-19 vaccination in CLL. Methods: The presence of the spike antibodies was assessed at a median time of 14 days from the second vaccine dose of SARS-CoV2 in 70 CLL followed-up at a single institution. Results: The antibody response rate (RR) in CLL patients was 58.5%, compared to 100% of 57 healthy controls of the same sex and age (P< 0.0001). Patients treatment-naïve and those in sustained clinical remission after therapy had the highest RR (87.0% and 87.7%, respectively). In contrast, patients on therapy with a pathway inhibitor as monotherapy and those treated with an association of anti-CD20 antibody were unlikely to respond to the SARS-CoV-2 vaccine (52% and 10%, respectively). In multivariate analysis, early Rai stage (OR, 0.19 [0.05-0.79]; P=0.02) and no previous therapy (OR, 0.06[0.02-0.27]; P<0.0001) were found to be independent predictors of vaccination response. An increase in absolute NK cells (i.e., CD16/CD56 positive cells) in patients with a serological response was found following the second dose of vaccine (P=0.02). Conclusions: These results confirm that serological response to the BNT162b2 vaccine in patients with CLL is impaired. A third boosting vaccine dosage should be considered for these patients.

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Superior immunogenicity and effectiveness of the 3rd BNT162b2 vaccine dose

10.1101/2021.12.19.21268037 ◽

2021 ◽

Author(s):

Yaniv Lustig ◽

Tal Gonen ◽

Lilac Meltzer ◽

Mayan Gilboa ◽

Victoria Indenbaum ◽

...

Keyword(s):

Health Care Workers ◽

Neutralizing Antibodies ◽

Mixed Model ◽

Linear Mixed Model ◽

Vaccine Dose ◽

High Avidity ◽

Igg Antibodies ◽

The Third ◽

Care Workers

In a prospective cohort study involving 12,413 Health Care Workers (HCW), we assessed immunogenicity, vaccine-effectiveness (VE) and safety of the third BNT162b2 vaccine dose. One month after third dose, anti-RBD-IgG were induced 1.7-folds compared to one month after the second. A significant increase in avidity from 61.1% (95%CI:56.1-66.7) to 96.3% (95%CI:94.2-98.5) resulted in a 6.1-folds neutralizing antibodies induction. Linear mixed model demonstrated that the third dose elicited a greater response among HCW≥60 or those with ≥two comorbidities who had a lower response following the second dose. VE of the third dose relative to two doses was 85.6% (95% CI, 79.2-90.1%). No serious adverse effects were reported. These results suggest that the third dose is superior to the second dose in both quantity and quality of IgG-antibodies and safely boosts protection from SARS-CoV-2 infection by generating high avidity antibodies to levels that are not significantly different between healthy and vulnerable populations.

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Robust induction of B cell and T cell responses by a third dose of inactivated SARS-CoV-2 vaccine

10.1101/2021.09.12.21263373 ◽

2021 ◽

Cited By ~ 1

Author(s):

Yihao Liu ◽

Qin Zeng ◽

Caiguanxi Deng ◽

Mengyuan Li ◽

Liubing Li ◽

...

Keyword(s):

T Cells ◽

Neutralizing Antibodies ◽

Vaccination Schedule ◽

Immune Memory ◽

Severe Illness ◽

Inactivated Vaccine ◽

Serological Response ◽

Humoral Immune ◽

The Third

AbstractSARS-CoV-2 inactivated vaccines have shown remarkable efficacy in clinical trials, especially in reducing severe illness and casualty. However, the waning of humoral immunity over time has raised concern over the durability of immune memory following vaccination. Thus, we conducted a non-randomized trial among the healthcare professionals (HCWs) to investigate the long-term sustainability of SARS-CoV-2-specific B cells and T cells stimulated by inactivated vaccine and the potential need for a third booster dose for the HCWs. Although neutralizing antibodies elicited by the standard two-dose vaccination schedule dropped from a peak of 31.2 AU/ml to 9.2 AU/ml 5 months after the second vaccination, spike-specific memory B and T cells were still detectable, forming the basis for a quick recall response. As expected, the faded humoral immune response was vigorously elevated to 66.8 AU/ml by 7.2 folds 1 week after the third dose along with abundant spike-specific circulating follicular helper T cells in parallel. Meanwhile, spike-specific CD4+ and CD8+ T cells were also robustly elevated by 5.9 and 2.7 folds respectively. Robust expansion of memory pools by the third dose potentiated greater durability of protective immune responses. Another key finding in this trial was that HCWs with low serological response to 2 doses were not truly “no responders” but fully equipped with immune memory that could be quickly recalled by a third dose even 5 months after the second vaccination. Collectively, these data provide insights into the generation of long-term immunological memory by the inactivated vaccine, which has implications for future booster strategies that the frontline HCWs, individuals with low serological response to 2 dose of vaccine and immune compromised patients could benefit from a third dose of inactivated vaccine.

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Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with B-cell non-Hodgkin lymphoma

Blood Advances ◽

10.1182/bloodadvances.2021005094 ◽

2021 ◽

Vol 5 (16) ◽

pp. 3053-3061

Author(s):

C. Perry ◽

E. Luttwak ◽

R. Balaban ◽

G. Shefer ◽

M. M. Morales ◽

...

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Messenger Rna ◽

Vaccine Dose ◽

Humoral Response ◽

Response Rates ◽

Serological Response ◽

Healthy Controls ◽

Non Hodgkin Lymphoma ◽

Anti Cd20

Abstract Patients diagnosed with B-cell non-Hodgkin lymphoma (B-NHL), particularly if recently treated with anti-CD20 antibodies, are at risk of severe COVID-19 disease. Because studies evaluating humoral response to COVID-19 vaccine in these patients are lacking, recommendations regarding vaccination strategy remain unclear. The humoral immune response to BNT162b2 messenger RNA (mRNA) COVID-19 vaccine was evaluated in patients with B-NHL who received 2 vaccine doses 21 days apart and compared with the response in healthy controls. Antibody titer, measured by the Elecsys Anti-SARS-CoV-2S assay, was evaluated 2 to 3 weeks after the second vaccine dose. Patients with B-NHL (n = 149), aggressive B-NHL (a-B-NHL; 47%), or indolent B-NHL (i-B-NHL; 53%) were evaluated. Twenty-eight (19%) were treatment naïve, 37% were actively treated with a rituximab/obinutuzumab (R/Obi)–based induction regimen or R/Obi maintenance, and 44% had last been treated with R/Obi >6 months before vaccination. A seropositive response was achieved in 89%, 7.3%, and 66.7%, respectively, with response rates of 49% in patients with B-NHL vs 98.5% in 65 healthy controls (P < .001). Multivariate analysis revealed that longer time since exposure to R/Obi and absolute lymphocyte count ≥0.9 × 103/μL predicted a positive serological response. Median time to achieve positive serology among anti-CD20 antibody-treated patients was longer in i-B-NHL vs a-B-NHL. The humoral response to BNT162b2 mRNA COVID-19 vaccine is impaired in patients with B-NHL who are undergoing R/Obi treatment. Longer time since exposure to R/Obi is associated with improved response rates to the COVID-19 vaccine. This study is registered at www.clinicaltrials.gov as #NCT04746092.

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Importance of the second SARS-CoV-2 vaccination dose for achieving serological response in patients with rheumatoid arthritis and seronegative spondyloarthritis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-221347 ◽

2021 ◽

pp. annrheumdis-2021-221347

Author(s):

Elisabeth Simader ◽

Selma Tobudic ◽

Peter Mandl ◽

Helmuth Haslacher ◽

Thomas Perkmann ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Messenger Rna ◽

Inflammatory Arthritis ◽

Vaccine Dose ◽

Humoral Response ◽

Joint Diseases ◽

Serological Response ◽

Dmard Therapy ◽

Inflammatory Joint Diseases ◽

Seronegative Spondyloarthritis

ObjectivesTo assess the kinetics of humoral response after the first and second dose of messenger RNA (mRNA) vaccines in patients with inflammatory joint diseases compared with healthy controls (HC). To analyse factors influencing the quantity of the immune response.MethodsWe enrolled patients with rheumatoid arthritis (RA) and seronegative spondyloarthritis (SpA), excluding those receiving B-cell depleting therapies and assessed the humoral response to mRNA vaccines after the first and the second dose of the vaccine in terms of seroconversion rate and titre. We compared the results to a HC group and analysed the influence of therapies as well as other characteristics on the humoral response.ResultsSamples from 53 patients with RA, 46 patients with SpA and 169 healthy participants were analysed. Seroconversion rates after the first immunisation were only 54% in patients with inflammatory arthritis compared with 98% in the HC group. However, seroconversion rates were 100% in all groups after second immunisation. Patients developed reduced antibody titres after the first vaccination compared with HC, but there was no difference after the second dose. While disease modifying anti-rheumatic drug (DMARD) monotherapy did not affect antibody levels, seroconversion rates as well as titre levels were reduced in patients receiving a combination of DMARDs compared with HC.ConclusionsPatients with inflammatory joint diseases under DMARD therapy show impaired humoral responses to the first vaccine dose but excellent final responses to vaccination with mRNA vaccines. Therefore, the full course of two immunisations is necessary for efficient vaccination responses in patients with inflammatory arthritis under DMARD therapy.

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Neutralizing Antibody Response to Pseudotype SARS-CoV-2 Differs between mRNA-1273 and BNT162b2 COVID-19 Vaccines and by History of SARS-CoV-2 Infection

10.1101/2021.10.20.21265171 ◽

2021 ◽

Author(s):

Harmony L. Tyner ◽

Mark G. Thompson ◽

Jefferey L. Burgess ◽

Lauren Grant ◽

Manjusha Gaglani ◽

...

Keyword(s):

Antibody Response ◽

Messenger Rna ◽

Neutralizing Antibodies ◽

Geometric Mean ◽

Vaccine Dose ◽

Neutralizing Antibody ◽

Frontline Workers ◽

History Of ◽

Antibody Titers ◽

Polymerase Chain

Background: Data on the development of neutralizing antibodies against SARS-CoV-2 after SARS-CoV-2 infection and after vaccination with messenger RNA (mRNA) COVID-19 vaccines are limited. Methods: From a prospective cohort of 3,975 adult essential and frontline workers tested weekly from August, 2020 to March, 2021 for SARS-CoV-2 infection by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) assay irrespective of symptoms, 497 participants had sera drawn after infection (170), vaccination (327), and after both infection and vaccination (50 from the infection population). Serum was collected after infection and each vaccine dose. Serum-neutralizing antibody titers against USA-WA1/2020-spike pseudotype virus were determined by the 50% inhibitory dilution. Geometric mean titers (GMTs) and corresponding fold increases were calculated using t-tests and linear mixed effects models. Results: Among 170 unvaccinated participants with SARS-CoV-2 infection, 158 (93%) developed neutralizing antibodies (nAb) with a GMT of 1,003 (95% CI=766-1,315). Among 139 previously uninfected participants, 138 (99%) developed nAb after mRNA vaccine dose-2 with a GMT of 3,257 (95% CI = 2,596-4,052). GMT was higher among those receiving mRNA-1273 vaccine (GMT =4,698, 95%CI= 3,186-6,926) compared to BNT162b2 vaccine (GMT=2,309, 95%CI=1,825-2,919). Among 32 participants with prior SARS-CoV-2 infection, GMT was 21,655 (95%CI=14,766-31,756) after mRNA vaccine dose-1, without further increase after dose-2. Conclusions: A single dose of mRNA vaccine after SARS-CoV-2 infection resulted in the highest observed nAb response. Two doses of mRNA vaccine in previously uninfected participants resulted in higher nAb to SARS-CoV-2 than after one dose of vaccine or SARS-CoV-2 infection alone. Neutralizing antibody response also differed by mRNA vaccine product.

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Two doses of mRNA vaccine elicit cross-neutralizing memory B-cells against SARS-CoV-2 Omicron variant

10.1101/2021.12.24.474091 ◽

2021 ◽

Author(s):

Ryutaro Kotaki ◽

Yu Adachi ◽

Saya Moriyama ◽

Taishi Onodera ◽

Shuetsu Fukushi ◽

...

Keyword(s):

B Cell ◽

Neutralizing Antibodies ◽

Cell Subset ◽

Vaccine Dose ◽

Neutralizing Antibody ◽

Memory B Cell ◽

The Third ◽

Circulating Antibodies ◽

B Cell Subsets ◽

Memory Subset

SARS-CoV-2 Beta and Omicron variants have multiple mutations in the receptor-binding domain (RBD) allowing antibody evasion. Despite the resistance to circulating antibodies in those who received two doses of mRNA vaccine, the third dose prominently recalls cross-neutralizing antibodies with expanded breadth to these variants. Herein, we longitudinally profiled the cellular composition of persistent memory B-cell subsets and their antibody reactivity against these variants following the second vaccine dose. The vaccination elicited a memory B-cell subset with resting phenotype that dominated the other subsets at 4.9 months. Notably, most of the resting memory subset retained the ability to bind the Beta variant, and the memory-derived antibodies cross-neutralized the Beta and Omicron variants at frequencies of 59% and 29%, respectively. The preservation of cross-neutralizing antibody repertoires in the durable memory B-cell subset likely contributes to the prominent recall of cross-neutralizing antibodies following the third dose of the vaccine.

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