scholarly journals Magnitude and breadth of neutralizing antibody responses elicited by SARS-CoV-2 infection or vaccination

2022 ◽  
Author(s):  
Benjamin L. Sievers ◽  
Saborni Chakraborty ◽  
Yong Xue ◽  
Terri Gelbart ◽  
Joseph C. Gonzalez ◽  
...  
Keyword(s):  
Antibody Response ◽  
Pregnant Women ◽  
Neutralizing Antibody ◽  
Healthy Adults ◽  
Antibody Responses ◽  
Vaccine Responses ◽  
Viral Antigens ◽  
Substantial Heterogeneity ◽  
Over Time

Multiple SARS-CoV-2 variants that possess mutations associated with increased transmission and antibody escape have arisen over the course of the current pandemic. While the current vaccines have largely been effective against past variants, the number of mutations found on the Omicron (B.1.529) spike appear to diminish the efficacy of pre-existing immunity. Using pseudoparticles expressing the spike of several SARS-CoV-2 variants, we evaluated the magnitude and breadth of the neutralizing antibody response over time in naturally infected and in mRNA-vaccinated individuals. We observed that while boosting increases the magnitude of the antibody response to wildtype (D614), Beta, Delta and Omicron variants, the Omicron variant was the most resistant to neutralization. We further observed that vaccinated healthy adults had robust and broad antibody responses while responses were relatively reduced in vaccinated pregnant women, underscoring the importance of learning how to maximize mRNA vaccine responses in pregnant populations. Findings from this study show substantial heterogeneity in the magnitude and breadth of responses after infection and mRNA vaccination and may support the addition of more conserved viral antigens to existing SARS-CoV-2 vaccines.

scholarly journals Antibodies elicited by SARS-CoV-2 infection or mRNA vaccines have reduced neutralizing activity against Beta and Omicron pseudoviruses

2022 ◽  
Author(s):  
Benjamin L. Sievers ◽  
Saborni Chakraborty ◽  
Yong Xue ◽  
Terri Gelbart ◽  
Joseph C. Gonzalez ◽  
...  
Keyword(s):  
Antibody Response ◽  
Vesicular Stomatitis Virus ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Spike Protein ◽  
Vaccine Responses ◽  
Viral Antigens ◽  
Vesicular Stomatitis ◽  
Substantial Heterogeneity ◽  
Over Time

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that possess mutations associated with increased transmission and antibody escape have arisen over the course of the current pandemic. Although the current vaccines have largely been effective against past variants, the number of mutations found on the Omicron (B.1.1.529) spike protein appear to diminish the protection conferred by pre-existing immunity. Using vesicular stomatitis virus (VSV) pseudoparticles expressing the spike protein of several SARS-CoV-2 variants, we evaluated the magnitude and breadth of the neutralizing antibody response over time in individuals after infection and in mRNA-vaccinated individuals. We observed that boosting increases the magnitude of the antibody response to wildtype (D614), Beta, Delta, and Omicron variants; however, the Omicron variant was the most resistant to neutralization. We further observed that vaccinated healthy adults had robust and broad antibody responses whereas responses may have been reduced in vaccinated pregnant women, underscoring the importance of learning how to maximize mRNA vaccine responses in pregnant populations. Findings from this study show substantial heterogeneity in the magnitude and breadth of responses after infection and mRNA vaccination and may support the addition of more conserved viral antigens to existing SARS-CoV-2 vaccines.

scholarly journals Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population

2020 ◽  
Author(s):  
Sabra L. Klein ◽  
Andrew Pekosz ◽  
Han-Sol Park ◽  
Rebecca L. Ursin ◽  
Janna R. Shapiro ◽  
...  
Keyword(s):  
Antibody Response ◽  
Neutralizing Antibody ◽  
Neutralization Assay ◽  
Antibody Responses ◽  
Full Length ◽  
Neutralization Titer ◽  
Humoral Immune ◽  
Virus Neutralization Assay ◽  
Male Sex ◽  
Substantial Heterogeneity

AbstractConvalescent plasma is currently one of the leading treatments for COVID-19, but there is a paucity of data identifying therapeutic efficacy. A comprehensive analysis of the antibody responses in potential plasma donors and an understanding of the clinical and demographic factors that drive variant antibody responses is needed. Among 126 potential convalescent plasma donors, the humoral immune response was evaluated by a SARS-CoV-2 virus neutralization assay using Vero-E6-TMPRSS2 cells, commercial IgG and IgA ELISA to Spike (S) protein S1 domain (Euroimmun), IgA, IgG and IgM indirect ELISAs to the full-length S or S-receptor binding domain (S-RBD), and an IgG avidity assay. Multiple linear regression and predictive models were utilized to assess the correlations between antibody responses with demographic and clinical characteristics. IgG titers were greater than either IgM or IgA for S1, full length S, and S-RBD in the overall population. Of the 126 plasma samples, 101 (80%) had detectable neutralizing titers. Using neutralization titer as the reference, the sensitivity of the IgG ELISAs ranged between 95-98%, but specificity was only 20-32%. Male sex, older age, and hospitalization with COVID-19 were all consistently associated with increased antibody responses across the serological assays. Neutralizing antibody titers were reduced over time in contrast to overall antibody responses. There was substantial heterogeneity in the antibody response among potential convalescent plasma donors, but sex, age and hospitalization emerged as factors that can be used to identify individuals with a high likelihood of having strong antiviral antibody levels.One Sentence SummaryThere is substantial heterogeneity in the antibody response to SARS-CoV-2 infection, with greater antibody responses being associated with male sex, advancing age, and hospitalization with COVID-19.

scholarly journals Cytokine Profiles and Antibody Response Associated to Choclo Orthohantavirus Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Tybbysay P. Salinas ◽  
Jose L. Garrido ◽  
Jacqueline R. Salazar ◽  
Publio Gonzalez ◽  
Nicole Zambrano ◽  
...  
Keyword(s):  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Serum Levels ◽  
Mortality Rates ◽  
Antibody Responses ◽  
Cytokine Profiles ◽  
Th2 Cytokine ◽  
Igg1 Subclass ◽  
Asymptomatic Individuals

BackgroundNew World Hantaviruses (NWHs) are the etiological agent underlying hantavirus cardiopulmonary syndrome (HCPS), a severe respiratory disease with high mortality rates in humans. In Panama, infections with Choclo Orthohantavirus (CHOV) cause a much milder illness characterized by higher seroprevalence and lower mortality rates. To date, the cytokine profiles and antibody responses associated with this milder form of HCPS have not been defined. Therefore, in this study, we examined immune serological profiles associated with CHOV infections.MethodsFor this retrospective study, sera from fifteen individuals with acute CHOV-induced HCPS, were analyzed alongside sera from fifteen convalescent phase individuals and thirty-three asymptomatic, CHOV-seropositive individuals. Cytokine profiles were analyzed by multiplex immunoassay. Antibody subclasses, binding, and neutralization against CHOV-glycoprotein (CHOV-GP) were evaluated by ELISA, and flow cytometry.ResultsHigh titers of IFNγ, IL-4, IL-8, and IL-10 serum cytokines were found in the acute individuals. Elevated IL-4 serum levels were found in convalescent and asymptomatic seropositive individuals. High titers of IgG1 subclass were observed across the three cohorts analyzed. Neutralizing antibody response against CHOV-GP was detectable in few acute individuals but was strong in both convalescent and asymptomatic seropositive individuals.ConclusionA Th1/Th2 cytokine signature is characteristic during acute mild HCPS caused by CHOV infection. High expression of Th2 and IL-8 cytokines are correlated with clinical parameters in acute mild HCPS. In addition, a strong IL-4 signature is associated with different cohorts, including asymptomatic individuals. Furthermore, asymptomatic individuals presented high titers of neutralizing antibodies.

Interferon activation status underlies higher antibody response to viral antigens in patients with systemic lupus erythematosus receiving no or light treatment

Rheumatology ◽  
2020 ◽  
Author(s):  
Albin Björk ◽  
Rui Da Silva Rodrigues ◽  
Elina Richardsdotter Andersson ◽  
Jorge I Ramírez Sepúlveda ◽  
Johannes Mofors ◽  
...  
Keyword(s):  
Antibody Response ◽  
Specific Antibody ◽  
Lupus Erythematosus ◽  
Serum Proteins ◽  
Light Treatment ◽  
Antibody Responses ◽  
Type I ◽  
Specific Antibody Response ◽  
Viral Antigens

Abstract Objectives Infections have been proposed as an environmental risk factor for autoimmune disease. Responses to microbial antigens may be studied in vivo during vaccination. We therefore followed patients with SLE and controls during split-virion influenza vaccination to quantify antibody responses against viral antigens and associated cellular and proteome parameters. Methods Blood samples and clinical data were collected from female patients with SLE with no or HCQ and/or low-dose prednisolone treatment (n = 29) and age- and sex-matched healthy controls (n = 17). Vaccine-specific antibody titres were measured by ELISA and IFN-induced gene expression in monocytes by quantitative PCR. Serum proteins were measured by proximity extension assay and disease-associated symptoms were followed by questionnaires. Results The vaccine-specific antibody response was significantly higher in patients compared with controls and titres of IgG targeting the viral proteins were higher in patients than controls at both 1 and 3 months after immunization. Clinical disease symptoms and autoantibody titres remained unchanged throughout the study. Notably, a positive pre-vaccination mRNA-based IFN score was associated with a significantly higher vaccine-specific antibody response and with a broader profile of autoantibody specificities. Screening of serum protein biomarkers revealed higher levels of IFN-regulated proteins in patients compared with controls and that levels of such proteins correlated with the vaccine-specific IgG response, with C-C motif chemokine ligand 3 exhibiting the strongest association. Conclusion Augmented antibody responses to viral antigens develop in patients with SLE on no or light treatment and associate with markers of type I IFN system activation at the RNA and protein levels.

scholarly journals Neutralizing antibody responses to enterovirus and adenovirus in healthy adults in China

2014 ◽  
Vol 3 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Xiang Wang ◽  
Man Xing ◽  
Chao Zhang ◽  
Yong Yang ◽  
Yudan Chi ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Healthy Adults ◽  
Antibody Responses

scholarly journals Modified Vaccinia Ankara Based SARS-CoV-2 Vaccine Expressing Full-Length Spike Induces Strong Neutralizing Antibody Response

2020 ◽  
Author(s):  
Nanda Kishore Routhu ◽  
Sailaja Gangadhara ◽  
Narayanaiah Cheedarla ◽  
Ayalnesh Shiferaw ◽  
Sheikh Abdul Rahman ◽  
...  
Keyword(s):  
Antibody Response ◽  
Room Temperature ◽  
Vaccine Candidate ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Full Length ◽  
Spike Protein ◽  
Strongly Correlated ◽  
Igg Antibodies ◽  
Potential Vaccine

AbstractThere is a great need for the development of vaccines for preventing SARS-CoV-2 infection and mitigating the COVID-19 pandemic. Here, we developed two modified vaccinia Ankara (MVA) based vaccines which express either a membrane anchored full-length spike protein (MVA/S) stabilized in a prefusion state or the S1 region of the spike (MVA/S1) which forms trimers and is secreted. Both immunogens contained the receptor-binding domain (RBD) which is a known target of antibody-mediated neutralization. Following immunizations with MVA/S or MVA/S1, both spike protein recombinants induced strong IgG antibodies to purified full-length SARS-CoV-2 spike protein. The MVA/S induced a robust antibody response to purified RBD, S1 and S2 whereas MVA/S1 induced an antibody response to the S1 region outside of the RBD region. Both vaccines induced an antibody response in the lung and that was associated with induction of bronchus-associated lymphoid tissue. MVA/S but not MVA/S1 vaccinated mice generated robust neutralizing antibody responses against SARS-CoV-2 that strongly correlated with RBD antibody binding titers. Mechanistically, S1 binding to ACE-2 was strong but reduced following prolonged pre-incubation at room temperature suggesting confirmation changes in RBD with time. These results demonstrate MVA/S is a potential vaccine candidate against SARS-CoV-2 infection.

scholarly journals Neutralizing antibody response in non-hospitalized SARS-CoV-2 patients

2020 ◽  
Author(s):  
Natalia Ruetalo ◽  
Ramona Businger ◽  
Karina Althaus ◽  
Simon Fink ◽  
Felix Ruoff ◽  
...  
Keyword(s):  
Antibody Response ◽  
Western Blot ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Virus Neutralization ◽  
Surrogate Markers ◽  
High Antibody ◽  
Serological Survey ◽  
Course Of Disease ◽  
Antibody Levels

The majority of infections with SARS-CoV-2 are asymptomatic or mild without the necessity of hospitalization. It is of importance to reveal if these patients develop an antibody response against SARS-CoV-2 and to define which antibodies confer virus neutralization. We conducted a comprehensive serological survey of 49 patients with a mild course of disease and quantified neutralizing antibody responses against a clinical SARS-CoV-2 isolate employing human cells as targets. Four patients (8%), even though symptomatic, did not develop antibodies against SARS-CoV-2 and two other patients (4%) were only positive in one of the six serological assays employed. For the remainder, antibody response against the S-protein correlated with serum neutralization whereas antibodies against the nucleocapsid were poor predictors of virus neutralization. Regarding neutralization, only six patients (12%) could be classified as highly neutralizers. Furthermore, sera from several individuals with fairly high antibody levels had only poor neutralizing activity. In addition, employing a novel serological Western blot system to characterize antibody responses against seasonal coronaviruses, we found that antibodies against the seasonal coronavirus 229E might contribute to SARS-CoV-2 neutralization. Altogether, we show that there is a wide breadth of antibody responses against SARS-CoV-2 in patients that differentially correlate with virus neutralization. This highlights the difficulty to define reliable surrogate markers for immunity against SARS-CoV-2.

scholarly journals Potent anti-SARS-CoV-2 Antibody Responses are Associated with Better Prognosis in Hospital Inpatient COVID-19 Disease

2020 ◽  
Author(s):  
Patrick J Tighe ◽  
Richard A Urbanowicz ◽  
Lucy Fairclough ◽  
C Patrick McClure ◽  
Brian J Thomson ◽  
...  
Keyword(s):  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Clinical Intervention ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Spike Protein ◽  
Effective Vaccine ◽  
Hospital Inpatient ◽  
Protein Variant ◽  
Immune Correlates

COVID-19 continues to cause a pandemic, having infected more than 20 million people globally. Successful elimination of the SARS-CoV-2 virus will require an effective vaccine. However, the immune correlates of infection are currently poorly understood. While neutralizing antibodies are believed to be essential for protection against infection, the contribution of the neutralizing antibody response to resolution of SARS-CoV-2 infection has not yet been defined. In this study the antibody responses to the SARS-CoV-2 spike protein and nucleocapsid proteins were investigated in a UK patient cohort, using optimised immunoassays and a retrovirus-based pseudotype entry assay. It was discovered that in severe COVID-19 infections an early antibody response to both antigens was associated with improved prognosis of infection. While not all SARS-CoV-2-reactive sera were found to possess neutralizing antibodies, neutralizing potency of sera was found to be greater in patients who went on to resolve infection, compared with those that died from COVID-19. Furthermore, viral genetic variation in spike protein was found to influence the production of neutralizing antibodies. Infection with the recently described spike protein variant 614G produced higher levels of neutralizing antibodies when compared to viruses possessing the 614D variant. These findings support the assertion that vaccines targeting generation of neutralizing antibodies may be useful at limiting SARS-CoV-2 infection. Assessment of the antibody responses to SARS-CoV-2 at time of diagnosis will be a useful addition to the diagnostic toolkit, enabling stratification of clinical intervention for severe COVID-19 disease.

scholarly journals The antibody response of rabbits to inactivated vaccinia virus

1965 ◽  
Vol 63 (4) ◽  
pp. 525-535 ◽  
Author(s):  
T. A. McNeill
Keyword(s):  
Antibody Response ◽  
Vaccinia Virus ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Single Factor

Inactivated vaccinia virus vaccines were prepared from purified virus inactivated by either formalin, hydroxylamine or heat. The immunogenicity of these vaccines was assessed in rabbits by measurement of virus neutralizing antibody following each of two inoculations. It was concluded that inactivated vaccinia virus stimulates the production of neutralizing antibody and that the most important single factor in this immunogenicity is the concentration of virus in the vaccine. Vaccines prepared from virus suspensions containing 107 to 108 pfu/ml. before inactivation give variable antibody responses.

scholarly journals Durability of antibody response to vaccination and surrogate neutralization of emerging variants based on SARS-CoV-2 exposure history

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thomas W. McDade ◽  
Alexis R. Demonbreun ◽  
Amelia Sancilio ◽  
Brian Mustanski ◽  
Richard T. D’Aquila ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Messenger Rna ◽  
Booster Vaccination ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Post Vaccination ◽  
Vaccine Responses ◽  
Clinical Protection ◽  
Exposure History ◽  
Antibody Levels

AbstractTwo-dose messenger RNA vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are highly effective in preventing symptomatic COVID-19 infection. However, the durability of protection is not known, nor is the effectiveness against emerging viral variants. Additionally, vaccine responses may differ based on prior SARS-CoV-2 exposure history. To investigate protection against SARS-CoV-2 variants we measured binding and neutralizing antibody responses following both vaccine doses. We document significant declines in antibody levels three months post-vaccination, and reduced neutralization of emerging variants, highlighting the need to identify correlates of clinical protection to inform the timing of and indications for booster vaccination.

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