Plasma neutralization properties of the SARS-CoV-2 Omicron variant

BACKGROUND The Omicron SARS-CoV-2 variant has spread internationally and is responsible for rapidly increasing case numbers. The emergence of divergent variants in the context of a heterogeneous and evolving neutralizing antibody response in host populations might compromise protection afforded by vaccines or prior infection. METHODS We measured neutralizing antibody titers in 169 longitudinally collected plasma samples using pseudotypes bearing the Wuhan-hu-1 or the Omicron variant or a laboratory-designed neutralization-resistant SARS-CoV-2 spike (PMS20). Plasmas were obtained from convalescents who did or did not subsequently receive an mRNA vaccine, or naive individuals who received 3-doses of mRNA or 1-dose Ad26 vaccines. Samples were collected approximately 1, 5-6 and 12 months after initial vaccination or infection. RESULTS Like PMS20, the Omicron spike protein was substantially resistant to neutralization compared to Wuhan-hu-1. In convalescent plasma the median deficit in neutralizing activity against PMS20 or Omicron was 30- to 60-fold. Plasmas from recipients of 2 mRNA vaccine doses were 30- to 180- fold less potent against PMS20 and Omicron than Wuhan-hu-1. Notably, previously infected or two-mRNA dose vaccinated individuals who received additional mRNA vaccine dose(s) had 38 to 154-fold and 35 to 214-fold increases in neutralizing activity against Omicron and PMS20 respectively. CONCLUSIONS Omicron exhibits similar distribution of sequence changes and neutralization resistance as does a laboratory-designed neutralization-resistant spike protein, suggesting natural evolutionary pressure to evade the human antibody response. Currently available mRNA vaccine boosters, that may promote antibody affinity maturation, significantly ameliorate SARS-CoV-2 neutralizing antibody titers.

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

Viruses ◽

10.3390/v13030422 ◽

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.

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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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Longitudinal variation in SARS-CoV-2 antibody levels and emergence of viral variants: implications for the ability of serological assays to predict immunity.

10.1101/2021.07.02.21259939 ◽

2021 ◽

Author(s):

Frauke Muecksch ◽

Helen Wise ◽

Kate Templeton ◽

Becky Batchelor ◽

Maria Squires ◽

...

Keyword(s):

High Throughput ◽

Neutralizing Antibody ◽

Spike Protein ◽

Serological Tests ◽

Neutralization Activity ◽

Neutralizing Activity ◽

Quantitative Measurements ◽

Antibody Titers ◽

Antibody Levels ◽

Selection Of

Background Serological assays are being deployed to monitor antibody responses in SARS-CoV-2 convalescents and vaccine recipients. There is a need to determine whether such assays can predict immunity, as antibody levels wane and viral variants emerge. Methods We measured antibodies in a cohort of SARS-CoV-2 infected patients using several high-throughput serological tests and functional neutralization assays. The effects of time and spike protein sequence variation on the performance and predictive value of the various assays was assessed. Findings Neutralizing antibody titers decreased over the first few months post-infection but stabilized thereafter, at about 30% of the level observed shortly after infection. Serological assays commonly used to measure antibodies against SARS-CoV-2 displayed a range of sensitivities that declined to varying extents over time. Quantitative measurements generated by serological assays based on the spike protein were better at predicting neutralizing antibody titers than assays based on nucleocapsid, but performance was variable and manufacturer positivity thresholds were not able to predict the presence or absence of detectable neutralizing activity. Even though there was some deterioration in correlation between serological measurements and functional neutralization activity, some assays maintained an ability to predict neutralizing titers, even against variants of concern. Interpretation The ability of high throughput serological assays to predict neutralizing antibody titers is likely crucial for evaluation of immunity at the population scale. These data will facilitate the selection of the most suitable assays as surrogates of functional neutralizing activity and suggest that such measurements may have utility in clinical practice.

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Loss of Neutralizing Antibody Response to mRNA Vaccination against SARS-CoV-2 Variants: Differing Kinetics and Strong Boosting by Breakthrough Infection

10.1101/2021.12.06.471455 ◽

2021 ◽

Author(s):

John P. Evans ◽

Cong Zeng ◽

Claire Carlin ◽

Gerard Lozanski ◽

Linda J. Saif ◽

...

Keyword(s):

Health Care ◽

Antibody Response ◽

Health Care Workers ◽

Vaccine Dose ◽

Neutralizing Antibody ◽

Breakthrough Infection ◽

Care Workers ◽

Antibody Titers ◽

Induced Immunity

AbstractThe waning efficacy of SARS-CoV-2 vaccines combined with the continued emergence of variants resistant to vaccine-induced immunity has reignited debate over the need for booster vaccines. To address this, we examined the neutralizing antibody (nAb) response against four major SARS-CoV-2 variants—D614G, Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2)—in health care workers (HCWs) at pre-vaccination, post-first and post-second mRNA vaccine dose, and six months post-second mRNA vaccine dose. Neutralizing antibody titers against all variants, especially the Delta variant, declined dramatically from four weeks to six months post-second mRNA vaccine dose. Notably, SARS-CoV-2 infection enhanced vaccine durability, and mRNA-1273 vaccinated HCWs also exhibited ~2-fold higher nAb titers than BNT162b2 vaccinated HCWs. Together these results demonstrate possible waning of protection from infection against SARS-CoV-2 Delta variant based on decreased nAb titers, dependent on COVID-19 status and the mRNA vaccine received.

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In vitro neutralizing activity of BNT162b2 mRNA-induced antibodies against full B.1.351 SARS-CoV-2 variant

10.22541/au.163881397.76967489/v1 ◽

2021 ◽

Author(s):

Federico García ◽

Esther Serrano-Conde ◽

Alba Leyva ◽

Ana Fuentes-Lopez ◽

Adolfo de Salazar ◽

...

Keyword(s):

Single Dose ◽

Antibody Response ◽

Neutralizing Antibodies ◽

Healthcare Workers ◽

Neutralizing Antibody ◽

Neutralization Activity ◽

Neutralizing Activity ◽

Study Participants ◽

Prior Infection

Background: SARS-CoV-2 variation represents a serious challenge to current COVID-19 vaccines. Recent reports suggest that B.1.351 and other variants may escape the neutralization activity of the antibodies generated by current vaccines. Methods: Ninety-nine healthcare workers undertaking BNT162b2 mRNA vaccination were sampled at baseline, on the day of the second dose, and 14 days after the latter. Neutralization activity against SARS-CoV-2 B.1, B.1.1.7 and B.1.351 was investigated using a Vero-E6 model. Results: Eleven of the study participants had prior infection with SARS-CoV-2. Neutralization titers against the B.1 and the B.1.1.7 variants were not statistically different and were significantly higher than titers against the B.1.351 variant across pre-exposed and non-pre-exposed vaccinated individuals ( p<0.01). While all vaccinated individuals presented neutralizing antibodies against B.1 and B 1.1.7 after the second dose, 14% were negative against B.1.351, and 76% had low titers (1/20-1/80). Pre-exposed vaccinated individuals showed higher titers than non-pre-exposed after the first (median titers of 1/387 versus 1/28, respectively) and the second doses (1/995 versus 1/703, respectively). As high as 72% of the pre-exposed vaccinees presented titers >1/80 after a single dose, while only 11% of non-exposed vaccinated individuals had titers >1/80. Conclusions: BNT162b2 mRNA-induced antibodies show a lower in vitro neutralizing activity against B.1.351 variant compared to neutralization against B.1.1.7 or B.1 variants. Interestingly, for individuals pre-exposed to SARS-CoV-2, one dose of BNT162b2 mRNA may be adequate to produce neutralizing antibodies against B.1.1.7 and B.1, while two doses of BNT162b2 mRNA provide optimal neutralizing antibody response against B.1.351 too.

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Serum Neutralizing Activity against B.1.1.7, B.1.351, and P.1 SARS-CoV-2 Variants of Concern in Hospitalized COVID-19 Patients

Viruses ◽

10.3390/v13071347 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1347

Author(s):

Claudia Maria Trombetta ◽

Serena Marchi ◽

Simonetta Viviani ◽

Alessandro Manenti ◽

Linda Benincasa ◽

...

Keyword(s):

Natural Infection ◽

Neutralizing Antibody ◽

Original Strain ◽

Immune Protection ◽

Serum Samples ◽

Symptomatic Infection ◽

Neutralizing Activity ◽

The United Kingdom ◽

Antibody Titers ◽

Pandemic Wave

The recent spreading of new SARS-CoV-2 variants, carrying several mutations in the spike protein, could impact immune protection elicited by natural infection or conferred by vaccination. In this study, we evaluated the neutralizing activity against the viral variants that emerged in the United Kingdom (B.1.1.7), Brazil (P.1), and South Africa (B.1.351) in human serum samples from hospitalized patients infected by SARS-CoV-2 during the first pandemic wave in Italy in 2020. Of the patients studied, 59.5% showed a decrease (≥2 fold) in neutralizing antibody titer against B.1.1.7, 83.3% against P.1, and 90.5% against B.1.351 with respect to the original strain. The reduction in antibody titers against all analyzed variants, and in particular P.1 and B.1.351, suggests that previous symptomatic infection might be not fully protective against exposure to SARS-CoV-2 variants carrying a set of relevant spike mutations.

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BACTERIAL AND VIRAL COPROANTIBODIES IN BREAST-FED INFANTS

PEDIATRICS ◽

10.1542/peds.39.2.202 ◽

1967 ◽

Vol 39 (2) ◽

pp. 202-213

Author(s):

Jean F. Kenny ◽

Mary I. Boesman ◽

Richard H. Michaels

Keyword(s):

Serum Antibody ◽

Neutralizing Antibody ◽

High Serum ◽

Maternal Milk ◽

Neutralizing Activity ◽

E Coli ◽

Immune Globulins ◽

Antibody Titers ◽

Human Immune ◽

Breast Fed

Stools of newborn breast-fed infants may contain significant amounts of hemagglutinating antibody to enteropathogenic E. coli and neutralizing antibody to polioviruses. Stool titers averaged only fourfold lower than maternal milk titers for antibacterial and less than twofold lower for antiviral activity. Similar ratios of stool:milk activity were also found for paired specimens obtained during the second and third postpartum months. The stool antibodies were stable at 56°C and exhibited definite specificity. Bacterial hemagglutinins in feces were more sensitive to mercaptoethanol than the poliovirus neutralizing activity. Stools from breast-fed infants contained gamma-1 globulins similar to those in milk, including IgA and small amounts of IgM. Meconium from bottle-fed infants with high serum antibody titers to polioviruses contained traces of homotypic neutralizing antibody. Antiviral and antibacterial activity were not detected in transitional and later stools from artificially fed infants, nor were human immune globulins. Milk bacterial hemagglutinating antibodies were more resistant to acid and to pepsin than those in serum. Furthermore, acid had a less deleterious effect on virus neutralizing activity in milk than it had on that in serum, and it also had less effect on the milk antiviral than on the milk antibacterial antibodies.

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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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Previous Infection Combined with Vaccination Produces Neutralizing Antibodies With Potency Against SARS-CoV-2 Variants

10.1101/2021.08.27.21262744 ◽

2021 ◽

Author(s):

F Javier Ibarrondo ◽

Christian Hofmann ◽

Ayub Ali ◽

Paul Ayoub ◽

Donald B Kohn ◽

...

Keyword(s):

Antiviral Activity ◽

Neutralizing Antibodies ◽

Spike Protein ◽

Original Sequence ◽

Neutralizing Activity ◽

Previous Infection ◽

Protein Mutations ◽

Antigenic Exposure ◽

Prior Infection ◽

Spike Sequence

SARS-CoV-2 continues to evolve in humans. Spike protein mutations increase transmission and potentially evade antibodies raised against the original sequence used in current vaccines. Our evaluation of serum neutralizing activity in both persons soon after SARS-CoV-2 infection (in April 2020 or earlier) or vaccination without prior infection confirmed that common spike mutations can reduce antibody antiviral activity. However, when the persons with prior infection were subsequently vaccinated, their antibodies attained an apparent biologic ceiling of neutralizing potency against all tested variants, equivalent to the original spike sequence. These findings indicate that additional antigenic exposure further improves antibody efficacy against variants.

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Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients

Science Translational Medicine ◽

10.1126/scitranslmed.abd5487 ◽

2020 ◽

Vol 12 (564) ◽

pp. eabd5487 ◽

Cited By ~ 20

Author(s):

Carl A. Pierce ◽

Paula Preston-Hurlburt ◽

Yile Dai ◽

Clare Burn Aschner ◽

Natalia Cheshenko ◽

...

Keyword(s):

T Cells ◽

Immune Responses ◽

Pediatric Patients ◽

Neutralizing Antibody ◽

Children And Youth ◽

Spike Protein ◽

Serum Concentrations ◽

Antiviral Immune Response ◽

Antibody Titers ◽

Ifn Γ

Children and youth infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have milder disease than do adults, and even among those with the recently described multisystem inflammatory syndrome, mortality is rare. The reasons for the differences in clinical manifestations are unknown but suggest that age-dependent factors may modulate the antiviral immune response. We compared cytokine, humoral, and cellular immune responses in pediatric (children and youth, age <24 years) (n = 65) and adult (n = 60) patients with coronavirus disease 2019 (COVID-19) at a metropolitan hospital system in New York City. The pediatric patients had a shorter length of stay, decreased requirement for mechanical ventilation, and lower mortality compared to adults. The serum concentrations of interleukin-17A (IL-17A) and interferon-γ (IFN-γ), but not tumor necrosis factor–α (TNF-α) or IL-6, were inversely related to age. Adults mounted a more robust T cell response to the viral spike protein compared to pediatric patients as evidenced by increased expression of CD25+ on CD4+ T cells and the frequency of IFN-γ+ CD4+ T cells. Moreover, serum neutralizing antibody titers and antibody-dependent cellular phagocytosis were higher in adults compared to pediatric patients with COVID-19. The neutralizing antibody titer correlated positively with age and negatively with IL-17A and IFN-γ serum concentrations. There were no differences in anti-spike protein antibody titers to other human coronaviruses. Together, these findings demonstrate that the poor outcome in hospitalized adults with COVID-19 compared to children may not be attributable to a failure to generate adaptive immune responses.

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