SARS-CoV-2 Convalescent Sera Binding and Neutralizing Antibody Concentrations Compared with COVID-19 Vaccine Efficacy Estimates Against Symptomatic Infection

Previous vaccine efficacy (VE) studies have estimated neutralizing and binding antibody concentrations that correlate with protection from symptomatic infection; how these estimates compare to those generated in response to SARS-CoV-2 infection is unclear. Here, we assessed quantitative neutralizing and binding antibody concentrations using standardized SARS-CoV-2 assays on 3,067 serum specimens collected during July 27, 2020-August 27, 2020 from COVID-19 unvaccinated persons with detectable anti-SARS-CoV-2 antibodies using qualitative antibody assays. Quantitative neutralizing and binding antibody concentrations were strongly positively correlated (r=0.76, p<0.0001) and were noted to be several fold lower in the unvaccinated study population as compared to published data on concentrations noted 28 days post-vaccination. In this convenience sample, ~88% of neutralizing and ~63-86% of binding antibody concentrations met or exceeded concentrations associated with 70% COVID-19 VE against symptomatic infection from published VE studies; ~30% of neutralizing and 1-14% of binding antibody concentrations met or exceeded concentrations associated with 90% COVID-19 VE. These data support observations of infection-induced immunity and current recommendations for vaccination post infection to maximize protection against symptomatic COVID-19.

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Predicting COVID-19 Vaccine Efficacy from Neutralizing Antibody Levels

10.1101/2021.10.13.21264921 ◽

2021 ◽

Author(s):

Majid R. Abedi ◽

Samuel Dixon ◽

Timothy Guyon ◽

Serene Hsu ◽

Aviva R. Jacobs ◽

...

Keyword(s):

High Throughput ◽

Vaccine Efficacy ◽

Neutralizing Antibodies ◽

Neutralization Test ◽

Neutralizing Antibody ◽

Published Data ◽

Real World Data ◽

Symptomatic Infection ◽

Viral Neutralization ◽

Antibody Levels

Recent studies using data accrued from global SARS-CoV-2 vaccination efforts have demonstrated that breakthrough infections are correlated with levels of neutralizing antibodies. The decrease in neutralizing antibody titers of vaccinated individuals over time, combined with the emergence of more infectious variants of concern has resulted in waning vaccine efficacy against infection and a rise in breakthrough infections. Here we use a combination of neutralizing antibody measurements determined by a high throughput surrogate viral neutralization test (sVNT) together with published data from vaccine clinical trials and comparative plaque reduction neutralization test (PRNT) between SARS-CoV-2 variants to develop a model for vaccine efficacy (VE) against symptomatic infection. Vaccine efficacy estimates using this model show good concordance with real world data from the US and Israel. Our work demonstrates that appropriately calibrated neutralizing antibody measurements determined by high throughput sVNT can be used to provide a semi-quantitative estimate of protection against infection. Given the highly variable antibody levels among the vaccinated population, this model may be of use in identification of individuals with an elevated risk of breakthrough infections.

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Dichotomy between the humoral and cellular responses elicited by mRNA and adenoviral vector vaccines against SARS-CoV-2

10.1101/2021.09.17.21263528 ◽

2021 ◽

Author(s):

Rahul Ukey ◽

Natalie Bruiners ◽

Hridesh Mishra ◽

Pankaj K. Mishra ◽

Deborah McCloskey ◽

...

Keyword(s):

Single Dose ◽

Adenoviral Vector ◽

Severe Disease ◽

Neutralizing Antibody ◽

Cellular Responses ◽

Real World Data ◽

Symptomatic Infection ◽

Cell Responses ◽

Binding Antibody ◽

Antibody Levels

AbstractProtection from severe disease and hospitalization by SARS-CoV-2 vaccination has been amply demonstrated by real-world data. However, the rapidly evolving pandemic raises new concerns. One pertains efficacy of adenoviral vector-based vaccines, particularly the single-dose Ad26.COV2.S, relative to mRNA vaccines. We investigated the immunogenicity of Ad26.COV2.S and mRNA vaccines in 33 subjects vaccinated with either vaccine class five months earlier on average. After controlling for time since vaccination, Spike-binding antibody and neutralizing antibody levels were higher in the mRNA-vaccinated subjects, while no significant differences in antigen-specific B cell and T cell responses were observed between the two groups. Thus, a dichotomy exists between humoral and cellular responses elicited by the two vaccine classes. Our results have implications for the need of booster doses in vaccinated subjects and might explain the dichotomy reported between the waning protection from symptomatic infection by SARS-CoV-2 vaccination and its persisting efficacy in preventing hospitalization and death.

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Mucosal Immunization Induces a Higher Level of Lasting Neutralizing Antibody Response in Mice by a Replication-Competent Smallpox Vaccine: Vaccinia Tiantan Strain

Journal of Biomedicine and Biotechnology ◽

10.1155/2011/970424 ◽

2011 ◽

Vol 2011 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Bin Lu ◽

Wenbo Yu ◽

Xiaoxing Huang ◽

Haibo Wang ◽

Li Liu ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Optimal Dose ◽

Smallpox Vaccine ◽

Smallpox Vaccination ◽

Post Vaccination ◽

Vaccination Programs ◽

Mucosal Vaccination ◽

First Time ◽

Induced Immunity

The possible bioterrorism threat using the variola virus, the causative agent of smallpox, has promoted us to further investigate the immunogenicity profiles of existing vaccines. Here, we study for the first time the immunogenicity profile of a replication-competent smallpox vaccine (vaccinia Tiantan, VTT strain) for inducing neutralizing antibodies (Nabs) through mucosal vaccination, which is noninvasive and has a critical implication for massive vaccination programs. Four different routes of vaccination were tested in parallel including intramuscular (i.m.), intranasal (i.n.), oral (i.o.), and subcutaneous (s.c.) inoculations in mice. We found that one time vaccination with an optimal dose of VTT was able to induce anti-VTT Nabs via each of the four routes. Higher levels of antiviral Nabs, however, were induced via the i.n. and i.o. inoculations when compared with the i.m. and s.c. routes. Moreover, the i.n. and i.o. vaccinations also induced higher sustained levels of Nabs overtime, which conferred better protections against homologous or alternating mucosal routes of viral challenges six months post vaccination. The VTT-induced immunity via all four routes, however, was partially effective against the intramuscular viral challenge. Our data have implications for understanding the potential application of mucosal smallpox vaccination and for developing VTT-based vaccines to overcome preexisting antivaccinia immunity.

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SARS-CoV-2 variants: levels of neutralisation required for protective immunity

10.1101/2021.08.11.21261876 ◽

2021 ◽

Author(s):

Deborah Cromer ◽

Megan Steain ◽

Arnold Reynaldi ◽

Timothy E Schlub ◽

Adam K Wheatley ◽

...

Keyword(s):

Vaccine Efficacy ◽

Severe Infection ◽

Booster Vaccination ◽

First Year ◽

Published Data ◽

Strongly Correlated ◽

Symptomatic Infection ◽

Clinical Protection ◽

Ancestral Virus

A number of SARS-CoV-2 variants of concern (VOC) have been identified that partially escape serum neutralisation activity elicited by current vaccines. Recent studies have also shown that vaccines demonstrate reduced protection against symptomatic infection with SARS-CoV-2 variants. Here we integrate published data on in vitro neutralisation and clinical protection to understand and predict vaccine efficacy against existing SARS-CoV-2 variants. We find that neutralising activity against the ancestral SARS-CoV-2 is highly predictive of neutralisation of the VOC, with all vaccines showing a similar drop in neutralisation to the variants. Neutralisation levels remain strongly correlated with protection from infection with SARS-CoV-2 VOC (r=0.81, p=0.0005). We apply an existing model relating in vitro neutralisation to protection (parameterised on data from ancestral virus infection) and find this remains predictive of vaccine efficacy against VOC once drops in neutralisation to the VOC are taken into account. Modelling of predicted vaccine efficacy against variants over time suggests that protection against symptomatic infection may drop below 50% within the first year after vaccination for some current vaccines. Boosting of previously infected individuals with existing vaccines (which target ancestral virus) has been shown to significantly increase neutralising antibodies. Our modelling suggests that booster vaccination should enable high levels of immunity that prevent severe infection outcomes with the current SARS-CoV-2 VOC, at least in the medium term.

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Evaluation of Humoral Immune Response after SARS-CoV-2 Vaccination Using Two Binding Antibody Assays and a Neutralizing Antibody Assay

Microbiology Spectrum ◽

10.1128/spectrum.01202-21 ◽

2021 ◽

Author(s):

Minjeong Nam ◽

Jong Do Seo ◽

Hee-Won Moon ◽

Hanah Kim ◽

Mina Hur ◽

...

Keyword(s):

Immune Response ◽

Severe Acute Respiratory Syndrome ◽

Humoral Immune Response ◽

Neutralization Test ◽

Neutralizing Antibody ◽

Virus Neutralization Test ◽

Antibody Assay ◽

Humoral Immune ◽

Antibody Assays ◽

Binding Antibody

The Siemens severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG (sCOVG; Siemens Healthcare Diagnostics Inc., NY, USA) and Abbott SARS-CoV-2 IgG II Quant (CoV-2 IgG II; Abbott Laboratories, Sligo, Ireland), which are automated, quantitative SARS-CoV-2-binding antibody assays, have been recently launched. This study aimed to evaluate the humoral immune response of BNT162b2 and ChAdOx1 nCoV-19 vaccines using sCOVG and CoV-2 IgG II and compare the quantitative values with the results of the GenScript surrogate virus neutralization test (cPASS; GenScript, USA Inc., NJ, USA).

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Longitudinal Serological Analysis and Neutralizing Antibody Levels in Coronavirus Disease 2019 Convalescent Patients

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa659 ◽

2020 ◽

Cited By ~ 6

Author(s):

Frauke Muecksch ◽

Helen Wise ◽

Becky Batchelor ◽

Maria Squires ◽

Elizabeth Semple ◽

...

Keyword(s):

Neutralizing Antibody ◽

Neutralization Titer ◽

Serological Assay ◽

Antibody Assays ◽

Antibody Titers ◽

Binding Antibody ◽

Antibody Levels ◽

Prior Infection ◽

Commercial Platform

Abstract Background Understanding the longitudinal trajectory of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies is crucial for diagnosis of prior infection and predicting future immunity. Methods We conducted a longitudinal analysis of coronavirus disease 2019 convalescent patients, with neutralizing antibody assays and SARS-CoV-2 serological assay platforms using SARS-CoV-2 spike (S) or nucleocapsid (N) antigens. Results Sensitivities of serological assays in diagnosing prior SARS-CoV-2 infection changed with time. One widely used commercial platform that had an initial sensitivity of >95% declined to 71% at 81–100 days after diagnosis. The trajectories of median binding antibody titers measured over approximately 3–4 months were not dependent on the use of SARS-CoV-2 N or S proteins as antigen. The median neutralization titer decreased by approximately 45% per month. Each serological assay gave quantitative antibody titers that were correlated with SARS-CoV-2 neutralization titers, but S-based serological assay measurements better predicted neutralization potency. Correlation between S-binding and neutralization titers deteriorated with time, and decreases in neutralization titers were not predicted by changes in S-binding antibody titers. Conclusions Different SARS-CoV-2 serological assays are more or less well suited for surveillance versus prediction of serum neutralization potency. Extended follow-up should facilitate the establishment of appropriate serological correlates of protection against SARS-CoV-2 reinfection.

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Anti-Spike protein assays to determine post-vaccination antibody levels: a head-to-head comparison of five quantitative assays

10.1101/2021.03.05.21252977 ◽

2021 ◽

Author(s):

Thomas Perkmann ◽

Nicole Perkmann-Nagele ◽

Thomas Koller ◽

Patrick Mucher ◽

Astrid Radakovics ◽

...

Keyword(s):

Operating Characteristics ◽

Vaccine Failure ◽

Individual Values ◽

Post Vaccination ◽

Characteristics Analysis ◽

Antibody Assays ◽

Binding Antibody ◽

Reliable Quantification ◽

Antibody Levels ◽

Protein Assays

AbstractBackgroundReliable quantification of the antibody response to SARS-CoV-2 vaccination is highly relevant for identifying possible vaccine failure and estimating the time of protection. Therefore, we aimed to evaluate the performance of five different Anti-SARS-CoV-2 antibody assays regarding the quantification of anti-spike (S) antibodies induced after a single dose of BNT162b2.MethodsSera of n=69 SARS-CoV-2 naïve individuals 21±1 days after vaccination with BNT162b2 (Pfizer/BioNTech) were tested using the following quantitative SARS-CoV-2 antibody assays: Roche S total antibody, DiaSorin trimeric spike IgG, DiaSorin S1/S2 IgG, Abbott II IgG, and Serion/Virion IgG. Test agreement was assessed by Passing-Bablok regression. Results were further compared to the percent inhibition calculated from a surrogate virus neutralization test (sVNT) by correlation and ROC (receiver-operating-characteristics) analysis.ResultsIndividual values were distributed over several orders of magnitude for all assays evaluated. Although the assays were in good overall agreement (ρ=0.80-0.94), Passing-Bablok regression revealed systematic and proportional differences, which could not be eliminated by converting the results to BAU/mL as suggested by the manufacturers. 7 (10%) individuals had a negative sVNT results (i.e. <30% inhibition). These samples were reliably identified by most assays and yielded low binding antibody levels (ROC-AUCs 0.84-0.93).ConclusionsAlthough all assays evaluated showed good correlation, readings from different assays were not interchangeable, even when converted to BAU/mL using the WHO international standard for SARS-CoV-2 immunoglobulin. This highlights the need for further standardization of SARS-CoV-2 serology.

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Contributions of lipopolysaccharide and the type IVB secretion system to Coxiella burnetii vaccine efficacy and reactogenicity

npj Vaccines ◽

10.1038/s41541-021-00296-6 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Carrie M. Long ◽

Paul A. Beare ◽

Diane C. Cockrell ◽

Jonathan Fintzi ◽

Mahelat Tesfamariam ◽

...

Keyword(s):

Phase I ◽

Coxiella Burnetii ◽

Vaccine Efficacy ◽

Q Fever ◽

Secretion System ◽

Cell Vaccine ◽

Post Vaccination ◽

Whole Cell Vaccine ◽

Type Ivb Secretion ◽

Type Ivb Secretion System

AbstractCoxiella burnetii is the bacterial causative agent of the zoonosis Q fever. The current human Q fever vaccine, Q-VAX®, is a fixed, whole cell vaccine (WCV) licensed solely for use in Australia. C. burnetii WCV administration is associated with a dermal hypersensitivity reaction in people with pre-existing immunity to C. burnetii, limiting wider use. Consequently, a less reactogenic vaccine is needed. Here, we investigated contributions of the C. burnetii Dot/Icm type IVB secretion system (T4BSS) and lipopolysaccharide (LPS) in protection and reactogenicity of fixed WCVs. A 32.5 kb region containing 23 dot/icm genes was deleted in the virulent Nine Mile phase I (NMI) strain and the resulting mutant was evaluated in guinea pig models of C. burnetii infection, vaccination-challenge, and post-vaccination hypersensitivity. The NMI ∆dot/icm strain was avirulent, protective as a WCV against a robust C. burnetii challenge, and displayed potentially altered reactogenicity compared to NMI. Nine Mile phase II (NMII) strains of C. burnetii that produce rough LPS, were similarly tested. NMI was significantly more protective than NMII as a WCV; however, both vaccines exhibited similar reactogenicity. Collectively, our results indicate that, like phase I LPS, the T4BSS is required for full virulence by C. burnetii. Conversely, unlike phase I LPS, the T4BSS is not required for vaccine-induced protection. LPS length does not appear to contribute to reactogenicity while the T4BSS may contribute to this response. NMI ∆dot/icm represents an avirulent phase I strain with full vaccine efficacy, illustrating the potential of genetically modified C. burnetii as improved WCVs.

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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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Host Factors Impact Vaccine Efficacy: Implications for Seasonal and Universal Influenza Vaccine Programs

Journal of Virology ◽

10.1128/jvi.00797-19 ◽

2019 ◽

Vol 93 (21) ◽

Cited By ~ 15

Author(s):

Santosh Dhakal ◽

Sabra L. Klein

Keyword(s):

Influenza Virus ◽

Influenza Vaccine ◽

Virus Vaccine ◽

Vaccine Efficacy ◽

Public Health Problem ◽

Influenza Virus Vaccine ◽

Host Factors ◽

Influenza Vaccines ◽

Vaccine Type ◽

Induced Immunity

ABSTRACT Influenza is a global public health problem. Current seasonal influenza vaccines have highly variable efficacy, and thus attempts to develop broadly protective universal influenza vaccines with durable protection are under way. While much attention is given to the virus-related factors contributing to inconsistent vaccine responses, host-associated factors are often neglected. Growing evidences suggest that host factors including age, biological sex, pregnancy, and immune history play important roles as modifiers of influenza virus vaccine efficacy. We hypothesize that host genetics, the hormonal milieu, and gut microbiota contribute to host-related differences in influenza virus vaccine efficacy. This review highlights the current insights and future perspectives into host-specific factors that impact influenza vaccine-induced immunity and protection. Consideration of the host factors that affect influenza vaccine-induced immunity might improve influenza vaccines by providing empirical evidence for optimizing or even personalizing vaccine type, dose, and use of adjuvants for current seasonal and future universal influenza vaccines.

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