scholarly journals 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

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.

scholarly journals Antibody Response to the BNT162b2 mRNA COVID-19 Vaccine in Subjects with Prior SARS-CoV-2 Infection

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 422
Author(s):  
Federico Gobbi ◽  
Dora Buonfrate ◽  
Lucia Moro ◽  
Paola Rodari ◽  
Chiara Piubelli ◽  
...  
Keyword(s):  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Vaccine Dose ◽  
Neutralizing Antibody ◽  
Immune Memory ◽  
Effective Response ◽  
Infected People ◽  
Significant Difference ◽  
Antibody Titers

Although antibody levels progressively decrease following SARS-CoV-2 infection, the immune memory persists for months. Thus, individuals who naturally contracted SARS-CoV-2 are expected to develop a more rapid and sustained response to COVID-19 vaccines than naïve individuals. In this study, we analyzed the dynamics of the antibody response to the BNT162b2 mRNA COVID-19 vaccine in six healthcare workers who contracted SARS-CoV-2 in March 2020, in comparison to nine control subjects without a previous infection. The vaccine was well tolerated by both groups, with no significant difference in the frequency of vaccine-associated side effects, with the exception of local pain, which was more common in previously infected subjects. Overall, the titers of neutralizing antibodies were markedly higher in response to the vaccine than after natural infection. In all subjects with pre-existing immunity, a rapid increase in anti-spike receptor-binding domain (RBD) IgG antibodies and neutralizing antibody titers was observed one week after the first dose, which seemed to act as a booster. Notably, in previously infected individuals, neutralizing antibody titers 7 days after the first vaccine dose were not significantly different from those observed in naïve subjects 7 days after the second vaccine dose. These results suggest that, in previously infected people, a single dose of the vaccine might be sufficient to induce an effective response.

scholarly journals Immunogenicity in sheep of Uruguayan commercial vaccines against bovine alphaherpesvirus 1, 5 and bovine pestiviruses

2020 ◽  
Vol 50 (4) ◽  
Author(s):  
Ingryd Merchioratto ◽  
Alana de Almeida Aurélio ◽  
Janice Machado Villela ◽  
Nicole Vieira Stone ◽  
Isac Junior Roman ◽  
...  
Keyword(s):  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Serological Response ◽  
Serum Samples ◽  
Post Vaccination ◽  
Immunological Responses ◽  
Antibody Titers ◽  
Low Levels

ABSTRACT: The serological responses induced by four commercial inactivated Uruguayan vaccines against bovine alphaherpesviruses (BoHV)-1 and -5 and bovine pestiviruses (BVDV-1, BVDV-2, and HoBiPeV) were evaluated in sheep. Thirty-seven sheep were immunized twice (day 0 and 25) and their serum samples were tested at different intervals (days 0, 25, 40, 60, and 90) post-vaccination (PV). Among the four vaccines tested, only one (G4) could induce the production of moderate neutralizing antibody titers against BoHV-1 and -5 and BVDV-1 and -2. The G3 vaccine showed a neutralizing serological response against the bovine alphaherpesviruses only. The G1 and G2 vaccines produced extremely low levels of antibodies in a few vaccinated animals only (geometric mean titers (GMT) 2.2). Similar levels of immunological responses were induced by the G4 vaccine against BoHV-1 and -5, and titers of neutralizing antibodies induced in approximately 70% of the animals are known to confer protection (GMT > 8). For bovine pestiviruses, the vaccine stimulated response of G4 against BVDV-2 was higher compared to that against BVDV-1, and extremely low for HoBiPeV. The peak of neutralizing antibodies to BoHV-1 and BVDV-1 was observed on days 40 and 60 PV, respectively. Thereafter, a remarkably decrease in neutralizing antibody response was observed at day 90 PV. These results demonstrated that tested commercial Uruguayan vaccines did not induce a serological response of adequate magnitude and duration. Thus, it is important to periodically review formulations and compositions of commercial vaccines against bovine alphaherpesviruses and pestiviruses.

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

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.

scholarly journals Antibody titers measured by commercial assays are correlated with neutralizing antibody titers calibrated by international standards

2021 ◽  
Author(s):  
Yu-An Kung ◽  
Chung-Guei Huang ◽  
Sheng-Yu Huang ◽  
Kuan-Ting Liu ◽  
Peng-Nien Huang ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Diagnostic Techniques ◽  
International Standards ◽  
World Health ◽  
Serum Samples ◽  
Antibody Titers ◽  
Health Organization

The World Health Organization (WHO) has highlighted the importance of an international standard (IS) for SARS-CoV-2 neutralizing antibody titer detection, with the aim of calibrating different diagnostic techniques. In this study, IS was applied to calibrate neutralizing antibody titers (IU/mL) and binding antibody titers (BAU/mL) in response to SARS-CoV-2 vaccines. Serum samples were collected from participants receiving the Moderna (n = 20) and Pfizer (n = 20) vaccines at three time points: pre-vaccination, after one dose, and after two doses. We obtained geometric mean titers of 1404.16 and 928.75 IU/mL for neutralizing antibodies after two doses of the Moderna and Pfizer vaccines, respectively. These values provide an important baseline for vaccine development and the implementation of non-inferiority trials. We also compared three commercially available kits from Roche, Abbott, and MeDiPro for the detection of COVID-19 antibodies based on binding affinity to S1 and/or RBD. Our results demonstrated that antibody titers measured by commercial assays are highly correlated with neutralizing antibody titers calibrated by IS.

Prevalence and Persistence of Maternal Dengue Neutralizing Antibodies in Infants From Central and Southern Thailand: A Retrospective Cohort Study

2019 ◽  
Vol 31 (4) ◽  
pp. 288-295 ◽  
Author(s):  
Adrienne Guignard ◽  
François Haguinet ◽  
Stéphanie Wéry ◽  
Phirangkul Kerdpanich
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Maternal Antibodies ◽  
Childhood Immunization ◽  
Serum Samples ◽  
Denv Serotypes ◽  
Antibody Titers ◽  
Antibody Kinetics

Understanding maternal dengue virus (DENV) neutralizing antibody kinetics in infants remains timely to develop a safe and effective childhood immunization. This retrospective study evaluated the prevalence and persistence of maternal antibody titers against DENV serotypes 1 to 4 in 139 Thai infants at 2, 6, and 7 months of age, using serum samples collected in a vaccination trial ( http://clinicaltrials.gov ; NCT00197275). Neutralizing antibodies against all 4 DENV serotypes were detected in 87.8% and 22.9% of infants at 2 and 7 months, respectively. At 2 months, DENV-4 neutralizing antibody geometric mean titers were notably lower (80) compared with DENV-1 to DENV-3 (277-471). Our results corroborate previous findings that DENV-1 to DENV-4 maternal antibodies persist at 7 months despite titers decrease from 2 months onwards. As persisting maternal antibodies may inhibit immune responses in DENV-vaccinated infants, a comprehensive understanding of DENV antibody kinetics is required in the perspective of vaccine development for infants.

scholarly journals Neutralization of SARS-CoV-2 Omicron variant by sera from BNT162b2 or Coronavac vaccine recipients

2021 ◽  
Author(s):  
Lu Lu ◽  
Bobo Mok ◽  
Linlei Chen ◽  
Jacky Chan ◽  
Owen Tsang ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
World Health ◽  
Whole Genome Sequence ◽  
Live Virus ◽  
Significant Difference ◽  
Antibody Titers ◽  
Ancestral Virus ◽  
Health Organization

Background The SARS-CoV-2 Omicron variant, designated as a Variant of Concern(VOC) by the World Health Organization, carries numerous spike protein mutations which have been found to evade neutralizing antibodies elicited by COVID-19 vaccines. The susceptibility of Omicron variant by vaccine-induced neutralizing antibodies are urgently needed for risk assessment. Methods Omicron variant strains HKU691 and HKU344-R346K were isolated from patients using TMPRSS2-overexpressing VeroE6 cells. Whole genome sequence was determined using nanopore sequencing. Neutralization susceptibility of ancestral lineage A virus and the Omicron, Delta and Beta variants to sera from 25 BNT162b2 and 25 Coronavac vaccine recipients was determined using a live virus microneutralization assay. Results The Omicron variant strain HKU344-R346K has an additional spike R346K mutation, which is present in 8.5% of strains in GISAID database. Only 20% and 24% of BNT162b2 recipients had detectable neutralizing antibody against the Omicron variant HKU691 and HKU344-R346K, respectively, while none of the Coronavac recipients had detectable neutralizing antibody titer against either Omicron isolates. For BNT162b2 recipients, the geometric mean neutralization antibody titers(GMT) of the Omicron variant isolates(5.43 and 6.42) were 35.7-39.9-fold lower than that of the ancestral virus(229.4), and the GMT of both omicron isolates were significantly lower than those of the beta and delta variants. There was no significant difference in the GMT between HKU691 and HKU344-R346K. Conclusions Omicron variant escapes neutralizing antibodies elicited by BNT162b2 or CoronaVac. The additional R346K mutation did not affect the neutralization susceptibility. Our data suggest that the Omicron variant may be associated with lower COVID-19 vaccine effectiveness.

RESPIRATORY SYNCYTIAL VIRUS NEUTRALIZING ANTIBODIES IN PERSONS RESIDING IN CHICAGO, ILLINOIS

PEDIATRICS ◽  
1964 ◽  
Vol 34 (6) ◽  
pp. 761-770
Author(s):  
Marc Beem ◽  
Rosalie Egerer ◽  
Julia Anderson
Keyword(s):  
Virus Infection ◽  
Antibody Titer ◽  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Indirect Evidence ◽  
Neutralizing Antibody ◽  
Single Strain ◽  
Wild Strains ◽  
Antibody Titers ◽  
Syncytial Virus

The R.S. virus neutralization test was examined in terms of several factors bearing on the consistency and specificity of antibody response to a single strain (Randall) of this virus. It was found that this virus detected significant rises in antibody titer in 90% of 30 patients over 6 months of age who were infected with wild strains of R.S. virus between the years 1958 and 1962. Heterologous neutralizing antibodies to R.S. virus did not occur following human infections with various myxoviruses, adenoviruses, enteroviruses and herpesvirus. Indirect evidence was presented indicating that tile neutralizing activity of human serums is due to specific antibody and not due to non-specific, heat stable neutralizing substance. The titer of R.S. neutralizing antibodies was determined in the serums of 26 parturient mothers, and their 27 newborn babies, and 186 other individuals between the ages of 6 months and 69 years. Longitudinal observations of antibody titer were also conducted on 12 other infants. Neutralizing antibodies to R.S. virus were found to reach the term fetus at undiminished titer. In the longitudinal observations, serum neutralizing antibody titers were found to fall during the first months of life, decreasing by half in an average time of 43 days. Neutralizing antibodies, actively formed in response to R.S. virus infection, were observed to occur with rapidly increasing frequency in relation to age in subjects older than 6 months. These serologic findings indicated that among individuals residing in the metropolitan Chicago area, R.S. virus infection has been experienced by many during the first 2 years of life, most by school age, and all by 7 years of age. Geometric mean antibody titers were found to show a small, but probably significant, increase with age. The restriction of low titer reactors to pre-school children was noted. These serologic findings were interpreted as evidence that re-infections with R.S. virus occur, perhaps quite commonly.

scholarly journals LB11. A Single Dose of the MVA-BN Smallpox Vaccine Induces an Early Protective Antibody Response Similar to a Traditional Replicating Vaccine and Is Suitable for Emergency Scenarios

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S997-S998
Author(s):  
Jane Maclennan ◽  
Heinz Weidenthaler ◽  
Phillip Pittman ◽  
Darja Schmidt ◽  
Paul Chaplin
Keyword(s):  
Single Dose ◽  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Spontaneous Mutation ◽  
Neutralizing Antibody ◽  
Smallpox Vaccine ◽  
Group 2 ◽  
Emergency Scenarios ◽  
Group 1

Abstract Background Smallpox remains a high-priority threat due to its potential for re-emergence through events including bioterrorism and spontaneous mutation. While traditional replicating smallpox vaccines such as ACAM2000 are associated with serious side effects, the non-replicating MVA BN smallpox vaccine was developed as a safer alternative. Methods This phase 3 non-inferiority study compared indicators of efficacy between the MVA-BN smallpox vaccine and ACAM2000. The co-primary endpoints were (1) to compare vaccine-induced serum neutralizing antibodies (geometric mean titer [GMT]) at predefined Peak Visits, as measured by plaque reduction neutralization tests (PRNT) and (2) to assess the attenuation of ACAM2000-induced takes after MVA-BN administration by measuring maximum lesion area (MLA). Early neutralizing antibody GMTs at Day 14, a timepoint considered protective for traditional replicating smallpox vaccines, were also compared following single doses of either vaccine. Results A total of 440 subjects were evenly randomized to receive either 2 doses of MVA-BN followed by 1 dose of ACAM2000 at 4 week intervals (Group 1) or a single dose of ACAM2000 (Group 2). Peak neutralizing antibody GMTs were significantly higher following 2 MVA-BN doses (153.5) compared with ACAM2000 (79.3), with a ratio of 1.935 (95% CI: 1.562, 2.397). At Day 14, neutralizing antibody GMTs were equal following a single dose of either MVA BN or ACAM2000 (16.2, ratio of 0.997, 95% CI: 0.738, 1.348), with similar seroconversion rates (90.8% vs. 91.8%, respectively). The median MLA induced by ACAM2000 was significantly reduced when subjects received prior MVA-BN in Group 1 (0 mm2) compared with Group 2 (76.0 mm2), suggesting protection against orthopoxvirus. MVA BN was well tolerated, demonstrating a better safety profile than ACAM2000. Conclusion Two doses of MVA-BN induce significantly higher peak neutralizing antibody responses compared with ACAM2000. A single dose induces an early neutralizing antibody response equal to ACAM2000 at Day 14, demonstrating the suitability of MVA BN in both pre- and post-outbreak scenarios. This study was partly funded by BARDA under contract HHSO100200700034C. Disclosures Jane Maclennan, BSc MRPharmS, Bavarian Nordic (Employee), Bavarian Nordic (Employee, Shareholder), Heinz Weidenthaler, MD, Bavarian Nordic (Employee, Shareholder), Phillip Pittman, MD, Bavarian Nordic (Scientific Research Study Investigator), Darja Schmidt, PhD, Bavarian Nordic (Employee, Shareholder), Paul Chaplin, PhD, Bavarian Nordic (Board Member, Employee, Shareholder), Bavarian Nordic (Employee, Shareholder).

scholarly journals Ad26.COV2.S protects Syrian hamsters against G614 spike variant SARS-CoV-2 and does not enhance respiratory disease

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Joan E. M. van der Lubbe ◽  
Sietske K. Rosendahl Huber ◽  
Aneesh Vijayan ◽  
Liesbeth Dekking ◽  
Ella van Huizen ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Respiratory Disease ◽  
Syrian Hamster ◽  
Neutralizing Antibodies ◽  
Vaccine Dose ◽  
Neutralizing Antibody ◽  
Upper Respiratory Tract ◽  
Syrian Hamsters ◽  
Antibody Titers ◽  
Upper Respiratory

AbstractPreviously we have shown that a single dose of recombinant adenovirus serotype 26 (Ad26) vaccine expressing a prefusion stabilized SARS-CoV-2 spike antigen (Ad26.COV2.S) is immunogenic and provides protection in Syrian hamster and non-human primate SARS-CoV-2 infection models. Here, we investigated the immunogenicity, protective efficacy, and potential for vaccine-associated enhanced respiratory disease (VAERD) mediated by Ad26.COV2.S in a moderate disease Syrian hamster challenge model, using the currently most prevalent G614 spike SARS-CoV-2 variant. Vaccine doses of 1 × 109 and 1 × 1010 VP elicited substantial neutralizing antibodies titers and completely protected over 80% of SARS-CoV-2 inoculated Syrian hamsters from lung infection and pneumonia but not upper respiratory tract infection. A second vaccine dose further increased neutralizing antibody titers that was associated with decreased infectious viral load in the upper respiratory tract after SARS-CoV-2 challenge. Suboptimal non-protective immune responses elicited by low-dose A26.COV2.S vaccination did not exacerbate respiratory disease in SARS-CoV-2-inoculated Syrian hamsters with breakthrough infection. In addition, dosing down the vaccine allowed to establish that binding and neutralizing antibody titers correlate with lower respiratory tract protection probability. Overall, these preclinical data confirm efficacy of a one-dose vaccine regimen with Ad26.COV2.S in this G614 spike SARS-CoV-2 virus variant Syrian hamster model, show the added benefit of a second vaccine dose, and demonstrate that there are no signs of VAERD under conditions of suboptimal immunity.

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.

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