Reduced sera neutralization to Omicron SARS-CoV-2 by both inactivated and protein subunit vaccines and the convalescents

Omicron variant continues to spread all over the world. There are lots of scientific questions remaining to be answered for such a devastating variant. There are a dozen of vaccines already in clinical use. The very urgent scientific question would be whether or not these vaccines can protect Omicron variant. Here, we tested the sera from both convalescents and vaccine recipients receiving either inactivated or protein subunits vaccines (CoronaVac from Sinovac, or BBIBP-CoV from Sinopharm, or ZF2001 from Zhifei longcom) for the binding antibody titers (ELISA) and neutralization antibodies titers (pseudovirus neutralization assay). We showed that Omicron do have severe immune escape in convalescents, with 15 of 16 were negative in neutralization. By contrast, in vaccinees who received three jabs of inactivated or protein subunit vaccine, the neutralizing activity was much better preserved. Especially in the ZF2001 group with an extended period of the second and third jab (4-6 months) remains 100% positive in Omicron neutralization, with only 3.1-folds reduction in neutralizing antibody (NAb) titer. In this case, we proposed that, the multi-boost strategy with an extended interval between the second and third jab for immune maturation would be beneficial for NAb against devastating variants such as Omicron.

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Titers of Neutralizing Antibodies against SARS-CoV-2 Are Independent of Symptoms of Non-Severe COVID-19 in Young Adults

Viruses ◽

10.3390/v13020284 ◽

2021 ◽

Vol 13 (2) ◽

pp. 284

Author(s):

Hulda R. Jonsdottir ◽

Michel Bielecki ◽

Denise Siegrist ◽

Thomas W. Buehrer ◽

Roland Züst ◽

...

Keyword(s):

Young Adults ◽

Neutralizing Antibodies ◽

Severe Disease ◽

Humoral Response ◽

Neutralizing Antibody ◽

Neutralization Assay ◽

Asymptomatic Infection ◽

Homogeneous Population ◽

Humoral Immune ◽

Antibody Titers

Neutralizing antibodies are an important part of the humoral immune response to SARS-CoV-2. It is currently unclear to what extent such antibodies are produced after non-severe disease or asymptomatic infection. We studied a cluster of SARS-CoV-2 infections among a homogeneous population of 332 predominantly male Swiss soldiers and determined the neutralizing antibody response with a serum neutralization assay using a recombinant SARS-CoV-2-GFP. All patients with non-severe COVID-19 showed a swift humoral response within two weeks after the onset of symptoms, which remained stable for the duration of the study. One month after the outbreak, titers in COVID-19 convalescents did not differ from the titers of asymptomatically infected individuals. Furthermore, symptoms of COVID-19 did not correlate with neutralizing antibody titers. Therefore, we conclude that asymptomatic infection can induce the same humoral immunity as non-severe COVID-19 in young adults.

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Age-Dependent Evaluation of Immunoglobulin G Response after Chikungunya Virus Infection

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.20-1398 ◽

2021 ◽

Author(s):

Harshad P. Patil ◽

Mrunal Gosavi ◽

Akhilesh C. Mishra ◽

Vidya A. Arankalle

Keyword(s):

Acute Phase ◽

Chikungunya Virus ◽

Indirect Elisa ◽

Neutralizing Antibody ◽

Antibody Prevalence ◽

Exposure Age ◽

Age Dependent ◽

Antibody Titers ◽

Binding Antibody ◽

Acute Phase Serum

Current chikungunya antibody prevalence and titers are likely to differ based on exposure rates before the 2006 reemergence. For vaccine usage, such data are of immense importance. This study addresses age-stratified IgG titers and its subtypes in Pune, India, endemic for the disease. One hundred seventy serum pools (791 individuals with prior chikungunya exposure, age stratified) from exposed and 15 samples from acute disease phase were screened. Inactivated chikungunya virus (CHIKV)–based indirect ELISA was used to determine anti–CHIKV-IgG and its subtypes. Neutralizing antibody titers (plaque reduction neutralization test [PRNT]) were compared with binding antibody titers (ELISA). Anti–CHIKV-IgG titers along with IgG1 and IgG4 increased till the age-group of 11–15 years and remained comparable thereafter till > 65 years. IgG1 was the predominant IgG subtype detected in all the pools, whereas IgG4 was present in 151/170 pools. Strong correlation of IgG1 was obtained with CHIKV–PRNT50 titers. None of the sample had anti–CHIKV-IgG2, whereas five pools had IgG3 antibody. In the acute-phase serum sample, IgG1 was present in all the samples, whereas IgG4 was present in 8/15 samples. IgG4 was predominant in four samples. During acute phase and at different times postinfection, IgG1 circulated in high titers followed by IgG4. Higher antibody titers in adults reflect reexposures. The data will prove useful in assessing immune response to CHIKV vaccine.

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Seroprevalence to Measles Virus after Vaccination or Natural Infection in an Adult Population, in Italy

Vaccines ◽

10.3390/vaccines8010066 ◽

2020 ◽

Vol 8 (1) ◽

pp. 66 ◽

Cited By ~ 4

Author(s):

Gabriele Anichini ◽

Claudia Gandolfo ◽

Simonetta Fabrizi ◽

Giovan Battista Miceli ◽

Chiara Terrosi ◽

...

Keyword(s):

Measles Virus ◽

Natural Infection ◽

Adult Population ◽

Inverse Correlation ◽

Neutralizing Antibody ◽

Neutralization Assay ◽

Mmr Vaccine ◽

Serological Status ◽

Antibody Titers ◽

Efficacious Vaccine

An increase in measles cases worldwide, with outbreaks, has been registered in the last few years, despite the availability of a safe and highly efficacious vaccine. In addition to an inadequate vaccination coverage, even in high-income European countries studies proved that some vaccinated people were also found seronegative years after vaccination, thus increasing the number of people susceptible to measles infection. In this study, we evaluated the immunization status and the seroprevalence of measles antibodies among 1092 healthy adults, either vaccinated or naturally infected, in order to investigate the persistence of anti-measles IgG. Among subjects who received two doses of measles vaccine, the neutralizing antibody titer tended to decline over time. In addition, data collected from a neutralization assay performed on 110 healthy vaccinated subjects suggested an inverse correlation between neutralizing antibody titers and the time elapsed between the two vaccinations, with a significant decline in the neutralizing titer when the interval between the two doses was ≥11 years. On the basis of these results, monitoring the serological status of the population 10–12 years after vaccination could be important both to limit the number of people who are potentially susceptible to measles, despite the high efficacy of MMR vaccine, and to recommend a booster vaccine for the seronegatives.

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Statistical Approach To Estimate Vaccinia-Specific Neutralizing Antibody Titers Using a High-Throughput Assay

Clinical and Vaccine Immunology ◽

10.1128/cvi.00109-09 ◽

2009 ◽

Vol 16 (8) ◽

pp. 1105-1112 ◽

Cited By ~ 18

Author(s):

Richard Kennedy ◽

V. Shane Pankratz ◽

Eric Swanson ◽

David Watson ◽

Hana Golding ◽

...

Keyword(s):

Immune Responses ◽

Vaccinia Virus ◽

High Throughput ◽

Large Scale ◽

Statistical Approach ◽

Neutralizing Antibody ◽

Neutralization Assay ◽

Virus Neutralization Assay ◽

Antibody Titers ◽

High Throughput Assay

ABSTRACT Because of the bioterrorism threat posed by agents such as variola virus, considerable time, resources, and effort have been devoted to biodefense preparation. One avenue of this research has been the development of rapid, sensitive, high-throughput assays to validate immune responses to poxviruses. Here we describe the adaptation of a β-galactosidase reporter-based vaccinia virus neutralization assay to large-scale use in a study that included over 1,000 subjects. We also describe the statistical methods involved in analyzing the large quantity of data generated. The assay and its associated methods should prove useful tools in monitoring immune responses to next-generation smallpox vaccines, studying poxvirus immunity, and evaluating therapeutic agents such as vaccinia virus immune globulin.

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A SARS-CoV-2 spike ferritin nanoparticle vaccine protects hamsters against Alpha and Beta virus variant challenge

npj Vaccines ◽

10.1038/s41541-021-00392-7 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Kathryn McGuckin Wuertz ◽

Erica K. Barkei ◽

Wei-Hung Chen ◽

Elizabeth J. Martinez ◽

Ines Lakhal-Naouar ◽

...

Keyword(s):

Neutralizing Antibody ◽

High Dose ◽

Lung Pathology ◽

Vaccine Protection ◽

Virus Variant ◽

Syrian Golden Hamsters ◽

Antibody Titers ◽

Binding Antibody ◽

Adequate Coverage ◽

Dose Dependent

AbstractThe emergence of SARS-CoV-2 variants of concern (VOC) requires adequate coverage of vaccine protection. We evaluated whether a SARS-CoV-2 spike ferritin nanoparticle vaccine (SpFN), adjuvanted with the Army Liposomal Formulation QS21 (ALFQ), conferred protection against the Alpha (B.1.1.7), and Beta (B.1.351) VOCs in Syrian golden hamsters. SpFN-ALFQ was administered as either single or double-vaccination (0 and 4 week) regimens, using a high (10 μg) or low (0.2 μg) dose. Animals were intranasally challenged at week 11. Binding antibody responses were comparable between high- and low-dose groups. Neutralizing antibody titers were equivalent against WA1, B.1.1.7, and B.1.351 variants following two high dose vaccinations. Dose-dependent SpFN-ALFQ vaccination protected against SARS-CoV-2-induced disease and viral replication following intranasal B.1.1.7 or B.1.351 challenge, as evidenced by reduced weight loss, lung pathology, and lung and nasal turbinate viral burden. These data support the development of SpFN-ALFQ as a broadly protective, next-generation SARS-CoV-2 vaccine.

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Recombinant protein subunit SARS-CoV-2 vaccines formulated with CoVaccine HT adjuvant induce broad, Th1 biased, humoral and cellular immune responses in mice

10.1101/2021.03.02.433614 ◽

2021 ◽

Author(s):

Chih-Yun Lai ◽

Albert To ◽

Teri Ann S. Wong ◽

Michael M. Lieberman ◽

David E. Clements ◽

...

Keyword(s):

Vaccine Development ◽

Herd Immunity ◽

Neutralizing Antibody ◽

Protein Subunit ◽

Cellular Immune Responses ◽

Oil In Water ◽

History Of ◽

Antibody Titers ◽

Outbred Mice ◽

Cellular Immune

ABSTRACTThe speed at which several COVID-19 vaccines went from conception to receiving FDA and EMA approval for emergency use is an achievement unrivaled in the history of vaccine development. Mass vaccination efforts using the highly effective vaccines are currently underway to generate sufficient herd immunity and reduce transmission of the SARS-CoV-2 virus. Despite the most advanced vaccine technology, global recipient coverage, especially in resource-poor areas remains a challenge as genetic drift in naïve population pockets threatens overall vaccine efficacy. In this study, we described the production of insect-cell expressed SARS-CoV-2 spike protein ectodomain and examined its immunogenicity in mice. We demonstrated that, when formulated with CoVaccine HT™adjuvant, an oil-in-water nanoemulsion compatible with lyophilization, our vaccine candidates elicit a broad-spectrum IgG response, high neutralizing antibody titers, and a robust, antigen-specific IFN-γ secreting response from immune splenocytes in outbred mice. Our findings lay the foundation for the development of a dry-thermostabilized vaccine that is deployable without refrigeration.

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Commercial Serology Assays Predict Neutralization Activity Against SARS-CoV-2

10.1101/2020.07.10.20150946 ◽

2020 ◽

Cited By ~ 1

Author(s):

Raymond T Suhandynata ◽

Melissa A Hoffman ◽

Deli Huang ◽

Jenny T Tran ◽

Michael J Kelner ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Neutralization Assay ◽

Positive Serology ◽

Neutralization Activity ◽

Antibody Titers ◽

Negative Controls ◽

First Time ◽

The Relationship ◽

Positive Results

Background. Currently it is unknown whether a positive serology results correlates with protective immunity against SARS-CoV-2. There are also concerns regarding the low positive predictive value of SARS-CoV-2 serology tests, especially when testing populations with low disease prevalence. Methods. A neutralization assay was validated in a set of PCR confirmed positive specimens and in a negative cohort. 9,530 specimens were screened using the Diazyme SARS-CoV-2 IgG serology assay and all positive results (N=164) were reanalyzed using the neutralization assay, the Roche total immunoglobin assay, and the Abbott IgG assay. The relationship between the magnitude of a positive SARS-CoV-2 serology result and the levels of neutralizing antibodies detected was correlated. Neutralizing antibody titers (ID50) were also longitudinally monitored in SARS-CoV-2 PCR confirmed patients. Results. The SARS-CoV-2 neutralization assay had a PPA of 96.6% with a SARS-CoV-2 PCR test and a NPA of 98.0% across 100 negative controls. ID50 neutralization titers positively correlated with all three clinical serology platforms. Longitudinal monitoring of hospitalized PCR confirmed COVID-19 patients demonstrates they made high neutralization titers against SARS-CoV-2. PPA between the Diazyme IgG assay alone and the neutralization assay was 50.6%, while combining the Diazyme IgG assay with either the Roche or Abbott platforms increased the PPA to 79.2% and 78.4%, respectively. Conclusions. For the first time, we demonstrate that three widely available clinical serology assays positively correlate with SARS-CoV-2 neutralization activity observed in COVID-19 patients. When a two-platform screen and confirm approach was used for SARS-CoV-2 serology, nearly 80% of two-platform positive specimens had neutralization titers (ID50 >50).

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Inference of SARS-CoV-2 spike-binding neutralizing antibody titers in sera from hospitalized COVID-19 patients by using commercial enzyme and chemiluminescent immunoassays

10.1101/2020.09.07.20188151 ◽

2020 ◽

Author(s):

Arantxa Valdivia ◽

Ignacio Torres ◽

Victor Latorre ◽

Carla Frances-Gomez ◽

Eliseo Albert ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Neutralization Assay ◽

Virus Neutralization ◽

Pseudotyped Virus ◽

S Protein ◽

Neutralizing Activity ◽

Virus Neutralization Assay ◽

Degree Correlation ◽

Antibody Titers

Background: Whether antibody levels measured by commercially-available enzyme or chemiluminescent immunoassays targeting the SARS-CoV-2 spike (S) protein can act as a proxy for serum neutralizing activity remains to be established for many of these assays. Objectives: To evaluate the degree of correlation between neutralizing antibodies (NtAb) binding the SARS-CoV-2 Spike (S) protein and SARS-CoV-2-S-IgG levels measured by four commercial immunoassays in sera drawn from hospitalized COVID-19 patients. Patients and Methods: Ninety sera from 51 hospitalized COVID-19 patients were assayed by a pseudotyped virus neutralization assay, the LIAISON SARS-CoV-2 S1/S2 IgG, the Euroimmun SARS-CoV-2 IgG ELISA, the MAGLUMI 2019-nCoV IgG and the COVID-19 ELISA IgG assays. Results: Overall, the results obtained with the COVID-19 ELISA IgG test showed the highest agreement with the NtAb assay (κ, 0.85; 95% CI, 0.63-1). The most sensitive tests were the pseudotyped virus NtAb assay and the COVID-19 ELISA IgG assay (92.2% for both). Overall, the degree correlation between antibody titers resulting in 50% virus neutralization (NtAb50) in the pseudotyped virus assay and SARS-CoV-2 IgG levels was strong for the Euroimmun SARS-CoV-2 IgG ELISA (Rho=0.73) and moderate for the remaining assays (Rho=0.48 to 0.59). The kinetic profile of serum NtAb50 titers could not be reliably predicted by any of the SARS-CoV-2 IgG immunoassays. Conclusions: the suitability of SARS-CoV-2-S-IgG commercial immunoassays for inferring neutralizing activity of sera from hospitalized COVID-19 patients varies widely across tests and is influenced by the time of sera collection after the onset of symptoms.

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Sex disparities and neutralizing antibody durability to SARS-CoV-2 infection in convalescent individuals

10.1101/2021.02.01.21250493 ◽

2021 ◽

Author(s):

Alena J. Markmann ◽

Natasa Giallourou ◽

D. Ryan Bhowmik ◽

Yixuan J. Hou ◽

Aaron Lerner ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Human Antibody ◽

Antibody Titers ◽

Sex Disparities ◽

Binding Antibody ◽

Male Sex ◽

Antibody Levels ◽

First Time

AbstractThe coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has now caused over 2 million deaths worldwide and continues to expand. Currently, much is unknown about functionally neutralizing human antibody responses and durability to SARS-CoV-2. Using convalescent sera collected from 101 COVID-19 recovered individuals 21-212 days after symptom onset with forty-eight additional longitudinal samples, we measured functionality and durability of serum antibodies. We also evaluated associations between individual demographic and clinical parameters with functional neutralizing antibody responses to COVID-19. We found robust antibody durability out to six months, as well as significant positive associations with the magnitude of the neutralizing antibody response and male sex. We also show that SARS-CoV-2 convalescent neutralizing antibodies are higher in individuals with cardio-metabolic comorbidities.SignificanceIn this study we found that neutralizing antibody responses in COVID-19 convalescent individuals vary in magnitude but are durable and correlate well with RBD Ig binding antibody levels compared to other SARS-CoV-2 antigen responses. In our cohort, higher neutralizing antibody titers are independently and significantly associated with male sex compared to female sex. We also show for the first time, that higher convalescent antibody titers in male donors are associated with increased age and symptom grade. Furthermore, cardio-metabolic co-morbidities are associated with higher antibody titers independently of sex. Here, we present an in-depth evaluation of serologic, demographic, and clinical correlates of functional antibody responses and durability to SARS-CoV-2.

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Variable loss of antibody potency against SARS-CoV-2 B.1.1.529 (Omicron)

10.1101/2021.12.19.473354 ◽

2021 ◽

Author(s):

Daniel J. Sheward ◽

Changil Kim ◽

Roy A. Ehling ◽

Alec Pankow ◽

Xaquin Castro Dopico ◽

...

Keyword(s):

Healthcare Workers ◽

Blood Donors ◽

Neutralizing Antibody ◽

Neutralization Assay ◽

Antibody Responses ◽

Pseudotyped Virus ◽

Virus Neutralization Assay ◽

Form Part ◽

Antibody Titers ◽

Cross Neutralization

The recently-emerged SARS-CoV-2 B.1.1.529 variant (Omicron) is spreading rapidly in many countries, with a spike that is highly diverged from the pandemic founder, raising fears that it may evade neutralizing antibody responses. We cloned the Omicron spike from a diagnostic sample which allowed us to rapidly establish an Omicron pseudotyped virus neutralization assay, sharing initial neutralization results only 13 days after the variant was first reported to the WHO, 8 days after receiving the sample. Here we show that Omicron is substantially resistant to neutralization by several monoclonal antibodies that form part of clinical cocktails. Further, we find neutralizing antibody responses in pooled reference sera sampled shortly after infection or vaccination are substantially less potent against Omicron, with neutralizing antibody titers reduced by up to 45 fold compared to those for the pandemic founder. Similarly, in a cohort of convalescent sera prior to vaccination, neutralization of Omicron was low to undetectable. However, in recent samples from two cohorts from Stockholm, Sweden, antibody responses capable of cross-neutralizing Omicron were prevalent. Sera from infected-then-vaccinated healthcare workers exhibited robust cross-neutralization of Omicron, with an average potency reduction of only 5-fold relative to the pandemic founder variant, and some donors showing no loss at all. A similar pattern was observed in randomly sampled recent blood donors, with an average 7-fold loss of potency. Both cohorts showed substantial between-donor heterogeneity in their ability to neutralize Omicron. Together, these data highlight the extensive but incomplete evasion of neutralizing antibody responses by the Omicron variant, and suggest that increasing the magnitude of neutralizing antibody responses by boosting with unmodified vaccines may suffice to raise titers to levels that are protective.

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