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

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.

scholarly journals Superior immunogenicity and effectiveness of the 3rd BNT162b2 vaccine dose

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.

scholarly journals 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

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.

scholarly journals Seasonal Betacoronavirus Antibodies’ Expansion Post-BNT161b2 Vaccination Associates with Reduced SARS-CoV-2 VoC Neutralization

2022 ◽  
Author(s):  
Stefania Dispinseri ◽  
Ilaria Marzinotto ◽  
Cristina Brigatti ◽  
Maria Franca Pirillo ◽  
Monica Tolazzi ◽  
...  
Keyword(s):  
Health Care ◽  
Health Care Workers ◽  
Neutralizing Antibodies ◽  
Spike Protein ◽  
Post Vaccination ◽  
Care Workers ◽  
Sequential Samples ◽  
Alpha Beta ◽  
Antibody Levels ◽  
Neutralization Ability

AbstractSARS-CoV-2 vaccination is known to induce antibodies that recognize also variants of concerns (VoCs) of the virus. However, epidemiological and laboratory evidences indicate that these antibodies have a reduced neutralization ability against VoCs. We studied binding and neutralizing antibodies against the Spike protein domains and subunits of the Wuhan-Hu-1 virus and its alpha, beta, delta VoCs and of seasonal betacoronaviruses (HKU1 and OC43) in a cohort of 31 health care workers prospectively followed post-vaccination with BNT162b2-Comirnaty. The study of sequential samples collected up to 64 days post-vaccination showed that serological assays measuring IgG against Wuhan-Hu-1 antigens were a poor proxy for VoC neutralization. In addition, in subjects who had asymptomatic or mild COVID-19 prior to vaccination, the loss of nAbs following disease could be rapid and accompanied by post-vaccination antibody levels similar to those of naïve vaccinees. Interestingly, in health care workers naïve for SARS-CoV-2 infection, vaccination induced a rapid and transient reactivation of pre-existing seasonal coronaviruses IgG responses that was associated with a subsequent reduced ability to neutralize alpha and beta VoCs.

scholarly journals 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 ◽  
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.

scholarly journals Influence of past infection with SARS-CoV-2 on the response to the BioTech/ Pfizer BNT162b2 mRNA vaccine in health care workers: kinetics and durability of the humoral response

2021 ◽  
Author(s):  
Jesus Ontanon ◽  
Joaquin Blas ◽  
Carlos de Cabo ◽  
Celia Santos ◽  
Elena Ruiz-Escribano ◽  
...  
Keyword(s):  
Health Care ◽  
Antibody Response ◽  
Health Care Workers ◽  
Vaccine Dose ◽  
Immune Memory ◽  
Past Infection ◽  
Vaccination Programs ◽  
Care Workers ◽  
Previous Infection ◽  
Antibody Levels

Background: Vaccines against SARS-CoV-2 have provided an invaluable resource in the fight against this infection. Given the current vaccine shortage, vaccination programs must prioritize their distribution to the most appropriate segments of the population. Methods: We carried out a prospective cohort study with 63 health care workers (HCWs) from a public General Hospital. We compared antibody responses to two doses of BNT162b2 mRNA Covid-19 vaccine between HCWs with laboratory-confirmed SARS-CoV-2 infection before vaccination (experienced HCWs) and HCWs who were not previously infected (naive HCWs). Results: Seven days after the first vaccine dose HCWs with previous infection experienced a 126 fold increase in antibody levels (GMC 26955 AU; 95% CI 18785-35125). However, in the HCW naive group the response was much lower and only 5 of them showed positive antibody levels (>50 AU). The HCWs with previous infection did not significantly increased their antibody levels after the second dose while there was a significant increase in the naive HCW group (16 fold; GMC 20227 AU; 95% CI: 15179-25275). Approximately two months after completing vaccination, the level of antibodies was much lower in naive HCWs (GMC 6595 AU vs. 25003 AU; p<0.001) Conclusion: The study shows that 10 months after the disease has passed, the immune system is capable of producing a rapid and powerful secondary antibody response after one single dose of the vaccine. This response reflects the persistence of immunological memory and it is independent of whether or not anti-SARS-CoV-2 antibodies are detected in blood. Besides, we found that the second dose does not improve the antibody response in individuals with previous Covid-19 infection. Nonetheless, two months later, the persistence of antibody levels is still higher in the experienced HCWs. These data suggest that immune memory remains for a long time in recovered individuals, and therefore, vaccination in this group could be postponed until immunization of the rest of the population is complete.

scholarly journals SARS-CoV-2–Specific Neutralizing Antibody Responses in Norwegian Health Care Workers After the First Wave of COVID-19 Pandemic: A Prospective Cohort Study

2020 ◽  
Author(s):  
Mai-Chi Trieu ◽  
Amit Bansal ◽  
Anders Madsen ◽  
Fan Zhou ◽  
Marianne Sævik ◽  
...  
Keyword(s):  
Health Care ◽  
Cohort Study ◽  
Prospective Cohort Study ◽  
Health Care Workers ◽  
Prospective Cohort ◽  
Neutralizing Antibodies ◽  
Rt Pcr ◽  
Patient Exposure ◽  
Specific Antibodies ◽  
Care Workers

Abstract Background During the coronavirus disease 2019 (COVID-19) pandemic, many countries experienced infection in health care workers (HCW) due to overburdened health care systems. Whether infected HCW acquire protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Methods In a Norwegian prospective cohort study, we enrolled 607 HCW before and after the first COVID-19 wave. Exposure history, COVID-19–like symptoms, and serum samples were collected. SARS-CoV-2–specific antibodies were characterized by spike-protein IgG/IgM/IgA enzyme-linked immunosorbent and live-virus neutralization assays. Results Spike-specific IgG/IgM/IgA antibodies increased after the first wave in HCW with, but not in HCW without, COVID-19 patient exposure. Thirty-two HCW (5.3%) had spike-specific antibodies (11 seroconverted with ≥4-fold increase, 21 were seropositive at baseline). Neutralizing antibodies were found in 11 HCW that seroconverted, of whom 4 (36.4%) were asymptomatic. Ninety-seven HCW were tested by reverse transcriptase polymerase chain reaction (RT-PCR) during follow-up; 8 were positive (7 seroconverted, 1 had undetectable antibodies). Conclusions We found increases in SARS-CoV-2 neutralizing antibodies in infected HCW, especially after COVID-19 patient exposure. Our data show a low number of SARS-CoV-2–seropositive HCW in a low-prevalence setting; however, the proportion of seropositivity was higher than RT-PCR positivity, highlighting the importance of antibody testing.

scholarly journals More rapid, robust and sustainable antibody responses to mRNA COVID-19 vaccine in convalescent COVID-19 individuals

2021 ◽  
Author(s):  
Sabrina E Racine-Brzostek ◽  
Jim Yee ◽  
Ashley Sukhu ◽  
Yuqing Qiu ◽  
Sophie Rand ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Antibody Response ◽  
Real World ◽  
Neutralizing Antibodies ◽  
Vaccine Dose ◽  
Antibody Responses ◽  
Antibody Levels

Longitudinal studies are needed to evaluate the SARS-CoV-2 mRNA vaccine antibody response under real-world conditions. This longitudinal study investigated the quantity and quality of SARS-CoV-2 antibody response in 846 specimens from 350 subjects: comparing BNT162b2-vaccinated individuals (19 previously diagnosed with COVID-19 [RecoVax]; 49 never been diagnosed [NaiveVax]) to 122 hospitalized unvaccinated (HospNoVax) and 160 outpatient unvaccinated (OutPtNoVax) COVID-19 patients. NaiveVax experienced a delay in generating SARS-CoV-2 total antibody levels (TAb) and neutralizing antibodies (SNAb) after the 1st vaccine dose (D1), but a rapid increase in antibody levels was observed after the 2nd dose (D2). However, these never reached the robust levels observed in RecoVax. In fact, NaiveVax TAb and SNAb levels decreased 4-weeks post-D2 (p=0.003;p<0.001). For the most part, RecoVax TAb persisted throughout this study, after reaching maximal levels 2-weeks post-D2; but SNAb decreased significantly ~6-months post-D1 (p=0.002). Although NaiveVax avidity lagged behind that of RecoVax for most of the follow-up periods, NaiveVax did reach similar avidity by ~6-months post-D1. These data suggest that one vaccine dose elicits maximal antibody response in RecoVax and may be sufficient. Also, despite decreasing levels in TAb and SNAb overtime, long-term avidity maybe a measure worth evaluating and possibly correlating to vaccine efficacy.

scholarly journals Hepatitis B Virus Antibody Levels in High-Risk Health Care Workers

2011 ◽  
Vol 11 (8) ◽  
pp. 662-663 ◽  
Author(s):  
Esmaeil Mohammad Nejad ◽  
Sirous Jafari ◽  
Mahmood Mahmoodi ◽  
Jamaloddin Begjani ◽  
Seyyedeh Roghayyeh Ehsani ◽  
...  
Keyword(s):  
Health Care ◽  
Hepatitis B Virus ◽  
High Risk ◽  
Hepatitis B ◽  
Health Care Workers ◽  
Virus Antibody ◽  
Care Workers ◽  
B Virus ◽  
Antibody Levels

scholarly journals Emergency Response for Evaluating SARS-CoV-2 Immune Status, Seroprevalence and Convalescent Plasma in Argentina

2020 ◽  
Author(s):  
Diego S. Ojeda ◽  
María Mora Gonzalez Lopez Ledesma ◽  
Horacio Pallares ◽  
Guadalupe S. Costa Navarro ◽  
Lautaro Sanchez ◽  
...  
Keyword(s):  
Health Care ◽  
Immune Responses ◽  
Health Care Workers ◽  
Antibody Responses ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Care Workers ◽  
Antibody Titers ◽  
Health Institutions ◽  
Antibody Levels

ABSTRACTWe report the emergency development and application of a robust serologic test to evaluate acute and convalescent antibody responses to SARS-CoV-2 in Argentina. The assays, COVIDAR IgG and IgM, which were produced and provided for free to health authorities, private and public health institutions and nursing homes, use a combination of a trimer stabilized spike protein and the receptor binding domain (RBD) in a single enzyme-linked immunosorbent assay (ELISA) plate. Over half million tests have already been distributed to detect and quantify antibodies for multiple purposes, including assessment of immune responses in hospitalized patients and large seroprevalence studies in neighborhoods, slums and health care workers, which resulted in a powerful tool for asymptomatic detection and policy making in the country. Analysis of antibody levels and longitudinal studies of symptomatic and asymptomatic SARS-CoV-2 infections in over one thousand patient samples provided insightful information about IgM and IgG seroconversion time and kinetics, and IgM waning profiles. At least 35% of patients showed seroconversion within 7 days, and 95% within 45 days of symptoms onset, with simultaneous or close sequential IgM and IgG detection. Longitudinal studies of asymptomatic cases showed a wide range of antibody responses with median levels below those observed in symptomatic patients. Regarding convalescent plasma applications, a protocol was standardized for the assessment of end point IgG antibody titers with COVIDAR with more than 500 plasma donors. The protocol showed a positive correlation with neutralizing antibody titers, and was used to assess antibody titers for clinical trials and therapies across the country. Here, we demonstrate the importance of providing a robust and specific serologic assay for generating new information about antibody kinetics in infected individuals and mitigation policies to cope with pandemic needs.AUTHOR SUMMARYThe development of robust and specific serologic assays to detect antibodies to SARS-CoV-2 is essential to understand the pandemic evolution and to stablish mitigation strategies. Here, we report the emergency development, production and application of a versatile ELISA test for detecting antibodies against the whole spike protein and its receptor binding domain. Over half million tests have been freely distributed in public and private health institutions of Argentina for evaluating immune responses, convalescent plasma programs and for large seroprevalence studies in neighborhoods and health care workers. We are still learning how and when to use serologic testing in different epidemiological settings. This program allowed us to produce large amount of high quality data on antibody levels in symptomatic and asymptomatic SARS-CoV-2 infections and generate relevant information about IgM and IgG seroconversion time and kinetics. We also present standardized protocols for antibody quantification as guidance for convalescent donor plasma selection in hospitals throughout the country for compassionate use and clinical trials. Here, we provide a framework for generating widely available tools, protocols and information of antibody responses for pandemic management.

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