Superior immunogenicity and effectiveness of the 3rd BNT162b2 vaccine dose

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.

Download Full-text

Neutralizing antibodies to SARS-CoV-2 Omicron variant after 3rd mRNA vaccination in health care workers and elderly subjects and response to a single dose in previously infected adults

10.1101/2021.12.22.21268273 ◽

2021 ◽

Author(s):

Anu Haveri ◽

Anna Solastie ◽

Nina Ekström ◽

Pamela Österlund ◽

Hanna Nohynek ◽

...

Keyword(s):

Health Care ◽

Health Care Workers ◽

Neutralizing Antibodies ◽

Nursing Home Residents ◽

Vaccine Dose ◽

Spike Protein ◽

Wild Type Virus ◽

Elderly Subjects ◽

Igg Antibody ◽

Care Workers

The emergence of SARS-CoV-2 Omicron variant (B.1.1.529) with major spike protein mutations has raised concern over potential neutralization escape and breakthrough infections among vaccinated and previously SARS-CoV-2 infected subjects. We measured cross-protective antibodies against variants in health care workers (HCW, n=20) and nursing home residents (n=9) from samples collected 1-2 months following the booster (3rd) dose. We also assessed the antibody responses in prior to Omicron era infected subjects (n=38) with subsequent administration of a single mRNA vaccine dose. Following booster vaccination HCWs had high IgG antibody concentrations to the spike protein and neutralizing antibodies (NAb) were detectable against all variants. IgG concentrations among the elderly remained lower, and some lacked NAbs against the Beta and Omicron variants. NAb titers were significantly reduced against Delta, Beta and Omicron compared to wild-type virus regardless of age. Vaccination induced high IgG concentrations and variable titers of cross-reactive NAbs in previously infected subjects, whereas NAb titers against Omicron were barely detectable 1-month post-infection. High IgG concentrations with cross-protective neutralizing activity were detected after three COVID-19 vaccine doses in HCWs. However, lower NAb titers seen in the frail elderly suggest inadequate protection against Omicron breakthrough infections, yet protection against severe COVID-19 is expected.

Download Full-text

BNT162b2 SARS-CoV-2 Vaccination Elicits High Titers of Neutralizing Antibodies to Both B.1 and P.1 Variants in Previously Infected and Uninfected Subjects

Life ◽

10.3390/life11090896 ◽

2021 ◽

Vol 11 (9) ◽

pp. 896

Author(s):

Ilaria Vicenti ◽

Francesca Gatti ◽

Renzo Scaggiante ◽

Adele Boccuto ◽

Daniela Zago ◽

...

Keyword(s):

Health Care ◽

Health Care Workers ◽

Neutralizing Antibodies ◽

Vaccine Dose ◽

Neutralizing Antibody ◽

Post Vaccination ◽

Care Workers ◽

Antibody Titers ◽

Cross Neutralization ◽

Highly Correlated

We aimed to investigate neutralizing antibody titers (NtAbT) to the P.1 and B.1 SARS-CoV-2 variants in a cohort of healthy health care workers (HCW), including 20 previously infected individuals tested at baseline (BLinf, after a median of 298 days from diagnosis) and 21 days after receiving one vaccine dose (D1inf) and 15 uninfected subjects tested 21 days after the second-dose vaccination (D2uninf). All the subjects received BNT162b2 vaccination. D1inf NtAbT increased significantly with respect to BLinf against both B.1 and P.1 variants, with a fold-change significantly higher for P.1. D1inf NtAbT were significantly higher than D2uninf NtAbT, against B.1 and P.1. NtAbT against the two strains were highly correlated. P.1 NtAbT were significantly higher than B.1 NtAbT. This difference was significant for post-vaccination sera in infected and uninfected subjects. A single-dose BNT162b2 vaccination substantially boosted the NtAb response to both variants in the previously infected subjects. NtAb titers to B.1 and P.1 lineages were highly correlated, suggesting substantial cross-neutralization. Higher titers to the P.1 than to the B.1 strain were driven by the post-vaccination titers, highlighting that cross-neutralization can be enhanced by vaccination.

Download Full-text

Comparative analysis of BNT162b2, mRNA-1273 and ChAdOx1 COVID-19 vaccine induced antibody responses and the 3rd BNT162b2 vaccine induced neutralizing antibodies against Delta and Omicron variants

10.21203/rs.3.rs-1199296/v1 ◽

2022 ◽

Author(s):

Milja Belik ◽

Pinja Jalkanen ◽

Rickard Lundberg ◽

Arttu Reinholm ◽

Larissa Laine ◽

...

Keyword(s):

Health Care Workers ◽

Neutralizing Antibodies ◽

Vaccine Dose ◽

Adenovirus Vector ◽

Dose Interval ◽

Interval Group ◽

Care Workers ◽

Dosing Strategies ◽

Antibody Levels ◽

Multiple Variants

Abstract Two COVID-19 mRNA and two adenovirus vector vaccines have been licensed in Europe and various vaccine combinations and dosing strategies have been exploited to maximize the immunity against COVID-19. Here, we show that among health care workers (n=328) two doses of BNT162b2, mRNA-1273, or ChAdOx1 as also a combination of an adenovirus vector and mRNA vaccines induces equally high levels of anti-SARS-CoV-2 spike antibodies and neutralizing antibodies against B.1 and B.1.617.2 when administrated with a long 12-week dose interval. Two doses of BNT162b2 with a short 3-week interval induce 2-3-fold lower titers of neutralizing antibodies compared to the long interval. Third mRNA vaccine dose for the short dose interval group increased the antibody levels 4-fold compared to the levels after the second dose. Importantly, sera from all three-times vaccinated neutralized B.1.1.529 (Omicron). The data indicates that a third COVID-19 mRNA vaccine dose efficiently induces cross-protective neutralizing antibodies against multiple variants.

Download Full-text

Antibody Responses and Clinical Outcomes in Adults Hospitalized With Severe Coronavirus Disease 2019 (COVID-19): A Post hoc Analysis of LOTUS China Trial

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1247 ◽

2020 ◽

Cited By ~ 3

Author(s):

Lili Ren ◽

Guohui Fan ◽

Wenjuan Wu ◽

Li Guo ◽

Yeming Wang ◽

...

Keyword(s):

Viral Load ◽

Clinical Outcomes ◽

Neutralizing Antibodies ◽

Mixed Model ◽

Linear Mixed Model ◽

Protein S ◽

Statistical Correlation ◽

Immunoglobulin M ◽

Enzyme Linked Immunosorbent Assay ◽

Igg Antibodies

Abstract Background The characteristics of neutralizing antibodies (NAbs) and antibody against major antigen proteins related to clinical outcomes in severe coronavirus disease 2019 (COVID-19) patients were still less known. Methods NAbs and antibodies targeting nucleocapsid (N), spike protein (S), and the receptor-binding domain (RBD) in longitudinal plasma samples from the LOTUS China trial were measured by microneutralization assay and enzyme-linked immunosorbent assay (ELISA). Viral load was determined by real-time reverse transcription polymerase chain reaction (RT-PCR). A total of 576 plasma and 576 throat swabs were collected from 191 COVID-19 patients. Antibody titers related to adverse outcome and clinical improvement were analyzed. Multivariable adjusted generalized linear mixed model for random effects were developed. Results After day 28 post symptoms onset, the rate of antibody positivity reached 100% for RBD-immunoglobulin M (IgM), 97.8% for S-IgM, 100% for N-immunoglobulin G (IgG), 100% for RBD-IgG, 91.1% for N-IgM, and 91.1% for NAbs. The NAbs titers increased over time in both survivors and nonsurvivors and correlated to IgG antibodies against N, S, and RBD, whereas its presence showed no statistical correlation with death. N-IgG (slope −2.11, 95% confidence interval [CI] −3.04 to −1.18, P < .0001), S-IgG (slope −2.44, 95% CI −3.35 to −1.54, P < .0001), and RBD-IgG (slope −1.43, 95% CI −1.98 to −.88, P < .0001) were negatively correlated with viral load. S-IgG titers were lower in nonsurvivors than survivors (P = .020) at week 4 after symptoms onset. Conclusions IgM and IgG against N, S, and RBD and NAbs developed in most severe COVID-19 patients and do not correlate clearly with clinical outcomes. The levels of IgG antibodies against N, S, and RBD were related to viral clearance.

Download Full-text

BNT162b2 mRNA SARS-CoV-2 Vaccine Elicits High Avidity and Neutralizing Antibodies in Healthcare Workers

Vaccines ◽

10.3390/vaccines9060672 ◽

2021 ◽

Vol 9 (6) ◽

pp. 672

Author(s):

Federico Pratesi ◽

Teresita Caruso ◽

Davide Testa ◽

Tiziano Tarpanelli ◽

Alessandra Gentili ◽

...

Keyword(s):

Health Care ◽

Health Care Workers ◽

Neutralizing Antibodies ◽

Affinity Maturation ◽

High Avidity ◽

Pronounced Increase ◽

Antibody Persistence ◽

Care Workers ◽

Protective Antibodies ◽

Inhibitory Antibodies

The BNT162b2 vaccine, containing lipid nanoparticles-formulated mRNA encoding the full-length spike protein of SARS-CoV-2, has been employed to immunize health care workers in Italy, administered in two doses 21 days apart. In this study, we characterized the antibody response induced by the BNT162b2 vaccine in a group of health care workers, tested at baseline, after the first dose and after the booster. Thirty-nine subjects without previous exposure to SARS-CoV-2 were vaccinated with the BNT162b2 vaccine. IgM, IgG, and IgA anti-receptor binding domain (RBD) were tested by ELISA. Neutralizing antibodies were evaluated testing the inhibition of RBD binding to ACE2. Antibody avidity was measured by urea avidity ELISA. IgM anti-RBD are produced after the first dose of vaccine and persist after the booster. IgG and IgA anti-RBD antibodies are detected in high amounts in all the subjects after the first dose and further increase after the booster. A few subjects, already after the first dose, produce antibodies inhibiting RBD interaction with ACE2. After the booster, high levels of inhibitory antibodies are detected in all the subjects. Affinity maturation takes place with boosting and IgG anti-RBD avidity increases with the number of immunizations. A less pronounced increase is observed with IgA. These data indicate that the BNT162b2 vaccine can induce high levels of protective antibodies of high avidity in vaccinated subjects; both IgG and IgA anti-RBD antibodies are produced. Further studies are needed to evaluate antibody persistence over time.

Download Full-text

Nationwide Seroprevalence of SARS-CoV-2 IgG Antibodies among Four Groups of Primary Health-Care Workers and Their Household Contacts 6 Months after the Initiation of the COVID-19 Vaccination Campaign in France: SeroPRIM Study Protocol

Pathogens ◽

10.3390/pathogens10070911 ◽

2021 ◽

Vol 10 (7) ◽

pp. 911

Author(s):

Marie Pouquet ◽

Dorine Decarreaux ◽

Pol Prévot-Monsacré ◽

Corentin Hervé ◽

Andréas Werner ◽

...

Keyword(s):

Health Care ◽

Primary Health Care ◽

Health Care Workers ◽

Phase 1 ◽

Vaccination Campaign ◽

Igg Antibodies ◽

Household Contacts ◽

Primary Health ◽

Care Workers ◽

Natural Protection

Background: The protocol study will focus on the seroprevalence of IgG antibodies to SARS-CoV-2 achieved by vaccination and/or natural protection as well as the history, symptoms, and risk factors for SARS-CoV-2 in four primary health-care workers (PHCWs) and their household contacts in metropolitan France. Methods: Here, we propose a protocol for a nationwide survey to determine the seroprevalence of IgG antibodies to SARS-CoV-2 achieved by vaccination and/or natural protection in four PHCW populations (general practitioners, pediatricians, pharmacists and assistants, and dentists and assistants) and their household contacts. Participants will be included from June to July 2021 (Phase 1) among PHCW populations located throughout metropolitan France. They will be asked to provide a range of demographic and behavioral information since the first SARS-CoV-2 wave and a self-sampled dried blood spot. Phase 1 will involve also a questionnaire and serological study of PHCWs’ household contacts. Seroprevalence will be estimated using two ELISAs designed to detect specific IgG antibodies to SARS-CoV-2 in humoral fluid, and these results will be confirmed using a virus neutralization test. This study will be repeated from November to December 2021 (Phase 2) to evaluate the evolution of immune status achieved by vaccination and/or natural protection of PHCWs and to describe the history of exposure to SARS-CoV-2.

Download Full-text

Development of SARS-CoV-2 Specific IgG and Virus-Neutralizing Antibodies after Infection with Variants of Concern or Vaccination

Vaccines ◽

10.3390/vaccines9070700 ◽

2021 ◽

Vol 9 (7) ◽

pp. 700

Author(s):

Franziska Neumann ◽

Ruben Rose ◽

Janine Römpke ◽

Olaf Grobe ◽

Thomas Lorentz ◽

...

Keyword(s):

Immune Response ◽

Receptor Binding ◽

Neutralizing Antibodies ◽

Neutralization Test ◽

Vaccine Dose ◽

High Avidity ◽

Receptor Binding Domain ◽

Robust Immune Response ◽

Specific Igg ◽

Nucleoprotein N

The humoral immunity after SARS-CoV-2 infection or vaccination was examined. Convalescent sera after infection with variants of concern (VOCs: B.1.1.7, n = 10; B.1.351, n = 1) and sera from 100 vaccinees (Pfizer/BioNTech, BNT162b2, n = 33; Moderna, mRNA-1273, n = 11; AstraZeneca, ChAdOx1 nCoV-19/AZD1222, n = 56) were tested for the presence of immunoglobulin G (IgG) directed against the viral spike (S)-protein, its receptor-binding domain (RBD), the nucleoprotein (N) and for virus-neutralizing antibodies (VNA). For the latter, surrogate assays (sVNT) and a Vero-cell based neutralization test (cVNT) were used. Maturity of IgG was determined by measuring the avidity in an immunoblot (IB). Past VOC infection resulted in a broad reactivity of anti-S IgG (100%), anti-RBD IgG (100%), and anti-N IgG (91%), while latter were absent in 99% of vaccinees. Starting approximately two weeks after the first vaccine dose, anti-S IgG (75–100%) and particularly anti-RBD IgG (98–100%) were detectable. After the second dose, their titers increased and were higher than in the convalescents. The sVNT showed evidence of VNA in 91% of convalescents and in 80–100%/100% after first/second vaccine dose, respectively. After the second dose, an increase in VNA titer and IgGs of high avidity were demonstrated by cVNT and IB, respectively. Re-vaccination contributes to a more robust immune response.

Download Full-text

A Fumonisin Prevention Tool for Targeting and Ranking Agroclimatic Conditions Favoring Exposure in French Maize-Growing Areas

Toxins ◽

10.3390/toxins13030214 ◽

2021 ◽

Vol 13 (3) ◽

pp. 214

Author(s):

Agathe Roucou ◽

Christophe Bergez ◽

Benoît Méléard ◽

Béatrice Orlando

Keyword(s):

Mixed Model ◽

Linear Mixed Model ◽

Fusarium Verticillioides ◽

Agricultural Practices ◽

Climatic Conditions ◽

Agricultural Cooperatives ◽

Mixed Model Approach ◽

Food And Feed ◽

Model Approach

The levels of fumonisins (FUMO)—mycotoxins produced by Fusarium verticillioides—in maize for food and feed are subject to European Union regulations. Compliance with the regulations requires the targeting of, among others, the agroclimatic factors influencing fungal contamination and FUMO production. Arvalis-Institut du végétal has created a national, multiyear database for maize, based on field survey data collected since 2003. This database contains information about agricultural practices, climatic conditions and FUMO concentrations at harvest for 738 maize fields distributed throughout French maize-growing regions. A linear mixed model approach highlights the presence of borers and the use of a late variety, high temperatures in July and October, and a water deficit during the maize cycle as creating conditions favoring maize contamination with Fusarium verticillioides. It is thus possible to target a combination of risk factors, consisting of this climatic sequence associated with agricultural practices of interest. The effects of the various possible agroclimatic combinations can be compared, grouped and classified as promoting very low to high FUMO concentrations, possibly exceeding the regulatory threshold. These findings should facilitate the creation of a national, informative and easy-to-use prevention tool for producers and agricultural cooperatives to manage the sanitary quality of their harvest.

Download Full-text

ANALYSIS OF THE ROLE OF THE ECONOMIST IN PUBLIC HEALTH

Vestnik ◽

10.53065/kaznmu.2021.94.69.065 ◽

2021 ◽

pp. 313-316

Author(s):

И.Г. Турсумбай ◽

Л.К. Кошербаева

Keyword(s):

Public Health ◽

Health Care ◽

Comparative Analysis ◽

Health Economics ◽

Continuous Improvement ◽

Health Care Workers ◽

Economic Situation ◽

Care Workers

Одним из последствий осуществления медицинской деятельности в разнообразных хозяйственных формах является изменение экономического положения работников здравоохранения. От количества и качества их труда зависит экономический результат деятельности лечебно-профилактических учреждений (ЛПУ) в целом. В статье приводится сравнительный анализ занимающихся подготовкой экономистов в области здравоохранения по различным критериям. Подчеркивается необходимость непрерывного совершенствования подготовки управленческих кадров в области экономики здравоохранения в современных условиях развития общества. One of the consequences of the implementation of medical activities in various economic forms is a change in the economic situation of health care workers. The number and quality of their work depends on the economic result of the activities of medical and preventive institutions (LPU) as a whole. The article presents a comparative analysis of the health economists who are engaged in training according to various criteria. The necessity of continuous improvement of training of managerial personnel in the field of health economics in the modern conditions of society development is emphasized.

Download Full-text

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.

Download Full-text