scholarly journals SARS-CoV-2 binding and neutralizing antibody levels after vaccination with Ad26.COV2.S predict durable protection in rhesus macaques

2021 ◽  
Author(s):  
Ramon Roozendaal ◽  
Laura Solforosi ◽  
Daniel Stieh ◽  
Jan Serroyen ◽  
Roel Straetemans ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Preliminary Evidence ◽  
Correlates Of Protection ◽  
Antibody Titers ◽  
Antibody Levels ◽  
The Relationship

The first COVID-19 vaccines have recently gained authorization for emergency use.1,2 At this moment, limited knowledge on duration of immunity and efficacy of these vaccines is available. Data on other coronaviruses after natural infection suggest that immunity to SARS-CoV-2 might be short lived,3,4 and preliminary evidence indicates waning antibody titers following SARS-CoV-2 infection.5 Here we model the relationship between immunogenicity and protective efficacy of a series of Ad26 vectors encoding stabilized variants of the SARS-CoV-2 Spike (S) protein in rhesus macaques6,7,8 and validate the analyses by challenging macaques 6 months after immunization with the Ad26.COV2.S vaccine candidate that has been selected for clinical development. We find that Ad26.COV2.S confers durable protection against replication of SARS-CoV-2 in the lungs that is predicted by the levels of S-binding and neutralizing antibodies. These results suggest that Ad26.COV2.S could confer durable protection in humans and that immunological correlates of protection may enable the prediction of durability of protection.

scholarly journals SARS-CoV-2 binding and neutralizing antibody levels after Ad26.COV2.S vaccination predict durable protection in rhesus macaques

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ramon Roozendaal ◽  
Laura Solforosi ◽  
Daniel J. Stieh ◽  
Jan Serroyen ◽  
Roel Straetemans ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Preliminary Evidence ◽  
Correlates Of Protection ◽  
Antibody Titers ◽  
Antibody Levels ◽  
The Relationship

AbstractSeveral COVID-19 vaccines have recently gained authorization for emergency use. Limited knowledge on duration of immunity and efficacy of these vaccines is currently available. Data on other coronaviruses after natural infection suggest that immunity to SARS-CoV-2 might be short-lived, and preliminary evidence indicates waning antibody titers following SARS-CoV-2 infection. In this work, we model the relationship between immunogenicity and protective efficacy of a series of Ad26 vectors encoding stabilized variants of the SARS-CoV-2 Spike protein in rhesus macaques and validate the analyses by challenging macaques 6 months after immunization with the Ad26.COV2.S vaccine candidate that has been selected for clinical development. We show that Ad26.COV2.S confers durable protection against replication of SARS-CoV-2 in the lungs that is predicted by the levels of Spike-binding and neutralizing antibodies, indicating that Ad26.COV2.S could confer durable protection in humans and immunological correlates of protection may enable the prediction of durability of protection.

scholarly journals Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques

2021 ◽  
Author(s):  
Margherita Rosati ◽  
Mahesh Agarwal ◽  
Xintao Hu ◽  
Santhi Devasundaram ◽  
Dimitris Stellas ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Neutralizing Antibody ◽  
Anatomical Site ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Antibody Titers ◽  
Cellular Immune

The speed of development, versatility and efficacy of mRNA-based vaccines have been amply demonstrated in the case of SARS-CoV-2. DNA vaccines represent an important alternative since they induce both humoral and cellular immune responses in animal models and in human trials. We tested the immunogenicity and protective efficacy of DNA-based vaccine regimens expressing different prefusion-stabilized SARS-CoV-2 Spike antigens upon intramuscular injection followed by electroporation in rhesus macaques. Different Spike DNA vaccine regimens induced antibodies that potently neutralized SARS-CoV-2 in vitro and elicited robust T cell responses. The DNA-only vaccine regimens were compared to a regimen that included co-immunization of Spike DNA and protein in the same anatomical site, the latter of which showed significant higher antibody responses. All vaccine regimens led to control of SARS-CoV-2 intranasal/intratracheal challenge and absence of virus dissemination to the lower respiratory tract. Vaccine-induced binding and neutralizing antibody titers and antibody-dependent cellular phagocytosis inversely correlated with transient virus levels in the nasal mucosa. Importantly, the Spike DNA+Protein co-immunization regimen induced the highest binding and neutralizing antibodies and showed the strongest control against SARS-CoV-2 challenge in rhesus macaques.

scholarly journals Passive transfer of Ad26.COV2.S-elicited IgG from humans attenuates SARS-CoV-2 disease in hamsters

npj Vaccines ◽  
2022 ◽  
Vol 7 (1) ◽  
Author(s):  
Lisa H. Tostanoski ◽  
Abishek Chandrashekar ◽  
Shivani Patel ◽  
Jingyou Yu ◽  
Catherine Jacob-Dolan ◽  
...  
Keyword(s):  
Weight Loss ◽  
Adoptive Transfer ◽  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Specific Binding ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Transfer Model ◽  
Golden Syrian Hamster ◽  
Antibody Titers

AbstractSARS-CoV-2 Spike-specific binding and neutralizing antibodies, elicited either by natural infection or vaccination, have emerged as potential correlates of protection. An important question, however, is whether vaccine-elicited antibodies in humans provide direct, functional protection from SARS-CoV-2 infection and disease. In this study, we explored directly the protective efficacy of human antibodies elicited by Ad26.COV2.S vaccination by adoptive transfer studies. IgG from plasma of Ad26.COV2.S vaccinated individuals was purified and transferred into naïve golden Syrian hamster recipients, followed by intra-nasal challenge of the hamsters with SARS-CoV-2. IgG purified from Ad26.COV2.S-vaccinated individuals provided dose-dependent protection in the recipient hamsters from weight loss following challenge. In contrast, IgG purified from placebo recipients provided no protection in this adoptive transfer model. Attenuation of weight loss correlated with binding and neutralizing antibody titers of the passively transferred IgG. This study suggests that Ad26.COV2.S-elicited antibodies in humans are mechanistically involved in protection against SARS-CoV-2.

scholarly journals Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques

2021 ◽  
Vol 17 (9) ◽  
pp. e1009701
Author(s):  
Margherita Rosati ◽  
Mahesh Agarwal ◽  
Xintao Hu ◽  
Santhi Devasundaram ◽  
Dimitris Stellas ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Neutralizing Antibody ◽  
Anatomical Site ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Antibody Titers ◽  
Cellular Immune

The speed of development, versatility and efficacy of mRNA-based vaccines have been amply demonstrated in the case of SARS-CoV-2. DNA vaccines represent an important alternative since they induce both humoral and cellular immune responses in animal models and in human trials. We tested the immunogenicity and protective efficacy of DNA-based vaccine regimens expressing different prefusion-stabilized Wuhan-Hu-1 SARS-CoV-2 Spike antigens upon intramuscular injection followed by electroporation in rhesus macaques. Different Spike DNA vaccine regimens induced antibodies that potently neutralized SARS-CoV-2 in vitro and elicited robust T cell responses. The antibodies recognized and potently neutralized a panel of different Spike variants including Alpha, Delta, Epsilon, Eta and A.23.1, but to a lesser extent Beta and Gamma. The DNA-only vaccine regimens were compared to a regimen that included co-immunization of Spike DNA and protein in the same anatomical site, the latter of which showed significant higher antibody responses. All vaccine regimens led to control of SARS-CoV-2 intranasal/intratracheal challenge and absence of virus dissemination to the lower respiratory tract. Vaccine-induced binding and neutralizing antibody titers and antibody-dependent cellular phagocytosis inversely correlated with transient virus levels in the nasal mucosa. Importantly, the Spike DNA+Protein co-immunization regimen induced the highest binding and neutralizing antibodies and showed the strongest control against SARS-CoV-2 challenge in rhesus macaques.

scholarly journals Neutralizing Antibody Responses in COVID-19 Convalescent Sera

2020 ◽  
Vol 223 (1) ◽  
pp. 47-55 ◽  
Author(s):  
William T Lee ◽  
Roxanne C Girardin ◽  
Alan P Dupuis ◽  
Karen E Kulas ◽  
Anne F Payne ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
High Titer ◽  
Experimental Treatment ◽  
Neutralizing Antibody ◽  
Maximal Activity ◽  
The United States ◽  
Enzyme Linked Immunosorbent Assay ◽  
United States Food ◽  
Antibody Titers ◽  
Antibody Levels

Abstract Passive transfer of antibodies from COVID-19 convalescent patients is being used as an experimental treatment for eligible patients with SARS-CoV-2 infections. The United States Food and Drug Administration’s (FDA) guidelines for convalescent plasma initially recommended target antibody titers of 160. We evaluated SARS-CoV-2 neutralizing antibodies in sera from recovered COVID-19 patients using plaque reduction neutralization tests (PRNT) at moderate (PRNT50) and high (PRNT90) stringency thresholds. We found that neutralizing activity significantly increased with time post symptom onset (PSO), reaching a peak at 31–35 days PSO. At this point, the number of sera having neutralizing titers of at least 160 was approximately 93% (PRNT50) and approximately 54% (PRNT90). Sera with high SARS-CoV-2 antibody levels (>960 enzyme-linked immunosorbent assay titers) showed maximal activity, but not all high-titer sera contained neutralizing antibody at FDA recommended levels, particularly at high stringency. These results underscore the value of serum characterization for neutralization activity.

scholarly journals Functional antibody and T-cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study

2021 ◽  
Author(s):  
Annika Fendler ◽  
Lewis Au ◽  
Scott Shepherd ◽  
Fiona Byrne ◽  
Maddalena Cerrone ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Cellular Responses ◽  
Patients With Cancer ◽  
Cell Immunity ◽  
Clinical Annotation ◽  
Antibody Titers ◽  
Antibody Levels ◽  
Immune Profiling ◽  
Reactive Antibody

Abstract Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study (NCT03226886) integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2-positive, 94 were symptomatic and 2 patients died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies, 82% had neutralizing antibodies against WT, whereas neutralizing antibody titers (NAbT) against the Alpha, Beta, and Delta variants were substantially reduced. Whereas S1-reactive antibody levels decreased in 13% of patients, NAbT remained stable up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment-specific, but presented compensatory cellular responses, further supported by clinical. Overall, these findings advance the understanding of the nature and duration of immune response to SARS-CoV-2 in patients with cancer.

scholarly journals Protective efficacy of rhesus adenovirus COVID-19 vaccines against mouse-adapted SARS-CoV-2

2021 ◽  
Author(s):  
Lisa H. Tostanoski ◽  
Lisa E. Gralinski ◽  
David R. Martinez ◽  
Alexandra Schaefer ◽  
Shant H. Mahrokhian ◽  
...  
Keyword(s):  
Viral Replication ◽  
Protective Efficacy ◽  
Neutralizing Antibody ◽  
Wild Type ◽  
Adenovirus Serotype ◽  
Vaccine Candidates ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Antibody Titers ◽  
Adenovirus Vectors

The global COVID-19 pandemic has sparked intense interest in the rapid development of vaccines as well as animal models to evaluate vaccine candidates and to define immune correlates of protection. We recently reported a mouse-adapted SARS-CoV-2 virus strain (MA10) with the potential to infect wild-type laboratory mice, driving high levels of viral replication in respiratory tract tissues as well as severe clinical and respiratory symptoms, aspects of COVID-19 disease in humans that are important to capture in model systems. We evaluated the immunogenicity and protective efficacy of novel rhesus adenovirus serotype 52 (RhAd52) vaccines against MA10 challenge in mice. Baseline seroprevalence is lower for rhesus adenovirus vectors than for human or chimpanzee adenovirus vectors, making these vectors attractive candidates for vaccine development. We observed that RhAd52 vaccines elicited robust binding and neutralizing antibody titers, which inversely correlated with viral replication after challenge. These data support the development of RhAd52 vaccines and the use of the MA10 challenge virus to screen novel vaccine candidates and to study the immunologic mechanisms that underscore protection from SARS-CoV-2 challenge in wild-type mice. Importance We have developed a series of SARS-CoV-2 vaccines using rhesus adenovirus serotype 52 (RhAd52) vectors, which exhibits a lower seroprevalence than human and chimpanzee vectors, supporting their development as novel vaccine vectors or as an alternative Ad vector for boosting. We sought to test these vaccines using a recently reported mouse-adapted SARS-CoV-2 (MA10) virus to i) evaluate the protective efficacy of RhAd52 vaccines and ii) further characterize this mouse-adapted challenge model and probe immune correlates of protection. We demonstrate RhAd52 vaccines elicit robust SARS-CoV-2-specific antibody responses and protect against clinical disease and viral replication in the lungs. Further, binding and neutralizing antibody titers correlated with protective efficacy. These data validate the MA10 mouse model as a useful tool to screen and study novel vaccine candidates, as well as the development of RhAd52 vaccines for COVID-19.

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

2020 ◽  
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).

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

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.

scholarly journals Commercial Serology Assays Predict Neutralization Activity against SARS-CoV-2

2020 ◽  
Author(s):  
Raymond T Suhandynata ◽  
Melissa A Hoffman ◽  
Deli Huang ◽  
Jenny T Tran ◽  
Michael J Kelner ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Neutralization Assay ◽  
Negative Control ◽  
Percentage Agreement ◽  
Positive Serology ◽  
Neutralization Activity ◽  
Antibody Titers ◽  
The Relationship ◽  
Positive Results

Abstract Background It is unknown whether a positive serology result 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. In addition, 9530 specimens were screened using the Diazyme SARS-CoV-2 IgG serology assay and all positive results (N = 164 individuals) 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 neutralizing activity was determined. Neutralizing antibody titers (50% inhibitory dilution, ID50) were also longitudinally monitored in patients confirmed to have SARS-CoV-2 by PCR. Results The SARS-CoV-2 neutralization assay had a positive percentage agreement (PPA) of 96.6% with a SARS-CoV-2 PCR test and a negative percentage agreement (NPA) of 98.0% across 100 negative control individuals. ID50 neutralization titers positively correlated with all 3 clinical serology platforms. Longitudinal monitoring of hospitalized PCR-confirmed patients with COVID-19 demonstrated 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 These 3 clinical serology assays positively correlate with SARS-CoV-2 neutralization activity observed in patients with COVID-19. All patients confirmed SARS-CoV-2 positive by PCR develop neutralizing antibodies.

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