scholarly journals Humoral Response Induced by Prime-Boost Vaccination with the ChAdOx1 nCoV-19 and mRNA BNT162b2 Vaccines in a Teriflunomide-Treated Multiple Sclerosis Patient

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1140
Author(s):  
Yves Michiels ◽  
Nadhira Houhou-Fidouh ◽  
Gilles Collin ◽  
Jérôme Berger ◽  
Evelyne Kohli
Keyword(s):  
Multiple Sclerosis ◽  
Immune Responses ◽  
Antibody Response ◽  
Viral Vector ◽  
Humoral Response ◽  
Neutralizing Antibody ◽  
Protein S ◽  
Spike Protein ◽  
Vaccination Regimen ◽  
The Past

Patients with multiple sclerosis (MS) are treated with drugs that may impact immune responses to SARS-CoV-2 vaccination. Evaluation of “prime-boost” (heterologous) vaccination regimens including a first administration of a viral vector-based vaccine and a second one of an mRNA-based vaccine in such patients has not yet been completed. Here, we present the anti-spike protein S humoral response, including the neutralizing antibody response, in a 54-year-old MS patient who had been treated with teriflunomide for the past 2 years and who received a heterologous ChAdOx1 nCoV-19/ BNT162b2 vaccination regimen. The results showed a very strong anti-S IgG response and a good neutralizing antibody response. These results show that teriflunomide did not prevent the development of a satisfactory humoral response in this MS patient after vaccination with a ChAdOx1 nCoV-19/ BNT162b2 prime-boost protocol.

scholarly journals Antibody response to common viruses and human leukocyte antigen-DRB1 in pediatric multiple sclerosis

2012 ◽  
Vol 19 (7) ◽  
pp. 891-895 ◽  
Author(s):  
Emmanuelle Waubant ◽  
Ellen M Mowry ◽  
Lauren Krupp ◽  
Tanuja Chitnis ◽  
E Ann Yeh ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Antibody Response ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Humoral Response ◽  
Nuclear Antigen ◽  
Leukocyte Antigen ◽  
Epstein Barr ◽  
Humoral Responses ◽  
Hsv 1

Background: As remote infections with common herpes viruses are associated with modulation of the risk of multiple sclerosis (MS), we hypothesized that antibody concentrations against these viruses may further modify risk. As many common viruses are first encountered during childhood, pediatric MS offer a unique opportunity to investigate more closely their influence on susceptibility. Our aim was to determine if MS patients who were positive for these viruses had higher levels of antibodies to these viruses. We also assessed whether human leukocyte antigen (HLA)-DRB1*1501 genotype influenced viral antibody levels. Methods: Antibody response levels toward Epstein Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV)-1, and HLA-DRB1*1501 status were determined in pediatric MS patients ( n=189) and controls ( n=38). Multivariate analyses were used, adjusted for age, gender, race, ethnicity and use of disease-modifying therapies. Results: The antibody concentrations against EBV (Epstein-Barr nuclear antigen 1 (EBNA-1), viral capsid antigen (VCA) and early antigen (EA)), CMV and HSV-1 were similar between pediatric MS patients and controls positive for seroconversion against the virus of interest. EBNA-1 humoral responses were higher in HLA-DRB1 positive individuals ( p=0.005) whereas other viral humoral responses were similar in HLA-DRB1 positive and negative individuals. Conclusion: Among those positive for EBNA-1, MS patients did not have higher levels of antibody response to EBNA-1: however, titers for EBNA-1 were higher in those who were HLA-DRB1 positive. This suggests that genotype might influence the humoral response to EBV. Whether other genotypes influence antibody response to other viruses remains to be determined.

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

2020 ◽  
Vol 12 (564) ◽  
pp. eabd5487 ◽  
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.

scholarly journals Characterization of the Immune Response of MERS-CoV Vaccine Candidates Derived from Two Different Vectors in Mice

Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 125 ◽  
Author(s):  
Entao Li ◽  
Feihu Yan ◽  
Pei Huang ◽  
Hang Chi ◽  
Shengnan Xu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Antibody Response ◽  
Rabies Virus ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Viral Vector ◽  
Vaccine Vector ◽  
Vaccine Candidates ◽  
Cellular Immune Responses ◽  
Cellular Immune

Middle East respiratory syndrome (MERS) is an acute, high-mortality-rate, severe infectious disease caused by an emerging MERS coronavirus (MERS-CoV) that causes severe respiratory diseases. The continuous spread and great pandemic potential of MERS-CoV make it necessarily important to develop effective vaccines. We previously demonstrated that the application of Gram-positive enhancer matrix (GEM) particles as a bacterial vector displaying the MERS-CoV receptor-binding domain (RBD) is a very promising MERS vaccine candidate that is capable of producing potential neutralization antibodies. We have also used the rabies virus (RV) as a viral vector to design a recombinant vaccine by expressing the MERS-CoV S1 (spike) protein on the surface of the RV. In this study, we compared the immunological efficacy of the vaccine candidates in BALB/c mice in terms of the levels of humoral and cellular immune responses. The results show that the rabies virus vector-based vaccine can induce remarkably earlier antibody response and higher levels of cellular immunity than the GEM particles vector. However, the GEM particles vector-based vaccine candidate can induce remarkably higher antibody response, even at a very low dose of 1 µg. These results indicate that vaccines constructed using different vaccine vector platforms for the same pathogen have different rates and trends in humoral and cellular immune responses in the same animal model. This discovery not only provides more alternative vaccine development platforms for MERS-CoV vaccine development, but also provides a theoretical basis for our future selection of vaccine vector platforms for other specific pathogens.

scholarly journals Children with Invasive Staphylococcus aureus Disease Exhibit a Potently Neutralizing Antibody Response to the Cytotoxin LukAB

2013 ◽  
Vol 82 (3) ◽  
pp. 1234-1242 ◽  
Author(s):  
Isaac P. Thomsen ◽  
Ashley L. DuMont ◽  
David B. A James ◽  
Pauline Yoong ◽  
Benjamin R. Saville ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibody Response ◽  
High Titer ◽  
Humoral Response ◽  
Neutralizing Antibody ◽  
Human Neutrophils ◽  
Serum Samples ◽  
Marked Rise ◽  
Content Type

ABSTRACTDespite the importance ofStaphylococcus aureusas a common invasive bacterial pathogen, the humoral response to infection remains inadequately defined, particularly in children. The purpose of this study was to assess the humoral response to extracellular staphylococcal virulence factors, including the bicomponent leukotoxins, which are critical for the cytotoxicity ofS. aureustoward human neutrophils. Children with culture-provenS. aureusinfection were prospectively enrolled and stratified by disease type. Fifty-three children were enrolled in the study, of which 90% had invasive disease. Serum samples were obtained during the acute (within 48 h) and convalescent (4 to 6 weeks postinfection) phases, at which point both IgG titers againstS. aureusexotoxins were determined, and the functionality of the generated antibodies was evaluated. Molecular characterization of clinical isolates was also performed. We observed a marked rise in antibody titer from acute-phase to convalescent-phase sera for LukAB, the most recently describedS. aureusbicomponent leukotoxin. LukAB production by the isolates was strongly correlated with cytotoxicityin vitro, and sera containing anti-LukAB antibodies potently neutralized cytotoxicity. Antibodies toS. aureusantigens were detectable in healthy pediatric controls but at much lower titers than in sera from infected subjects. The discovery of a high-titer, neutralizing antibody response to LukAB during invasive infections suggests that this toxin is producedin vivoand that it elicits a functional humoral response.

scholarly journals Efficacy of a Third BNT162b2 mRNA COVID-19 Vaccine Dose in Patients with CLL who Failed Standard Two-dose Vaccination

Blood ◽  
2021 ◽  
Author(s):  
Yair Herishanu ◽  
Galia Rahav ◽  
Shai Levi ◽  
Andrei Braester ◽  
Gilad Itchaki ◽  
...  
Keyword(s):  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Response Rate ◽  
Vaccine Dose ◽  
Humoral Response ◽  
Response Rates ◽  
Lymphocytic Leukemia ◽  
Vaccination Regimen ◽  
The Third ◽  
Anti Cd20

Patients with chronic lymphocytic leukemia (CLL) have an impaired antibody response to COVID-19 vaccination. Here, we evaluated the antibody response to a third BNT162b2 mRNA vaccine in patients with CLL/small lymphocytic lymphoma (SLL) who failed to achieve a humoral response after standard two-dose vaccination regimen. Anti-SARS-CoV-2S and neutralizing antibodies were measured 3 weeks after administration of the third dose. In 172 patients with CLL the antibody response rate was 23.8%. Response rate among actively treated patients (12.0%, n=12/100) was lower compared to treatment-naïve patients (40.0%, n=16/40; OR=4.9, 95% CI 1.9-12.9; p&lt;0.001) and patients off-therapy (40.6%, n=13/32; OR=5.0, 95% CI 1.8-14.1; p&lt;0.001), (p&lt;0.001). In those actively treated with BTK inhibitors or venetoclax ± anti-CD20 antibody, response rates were extremely low (15.3%, n=9/59 and 7.7%, n=3/39, respectively). Only one of the 28 patients (3.6%) treated with anti-CD20 antibodies &lt;12 months prior to vaccination responded. The anti-SARS-CoV-2S antibody levels correlated linearly with neutralizing antibody titers (r=0.732, p&lt;0.001). In a multivariate analysis, the independent variables that were associated with response included lack of active therapy (OR=5.6, 95% CI 2.3-13.8; p&lt;0.001) and serum IgA levels ≥80 mg/dL (OR=5.8, 95% CI 2.1-15.9; p&lt;0.001) In conclusion, in patients with CLL/SLL who failed to achieve a humoral response after standard two-dose BNT162b2 mRNA vaccination regimen, close to a quarter responded to the third dose of vaccine. The antibody response rates were lower during active treatment and in patients with a recent exposure (&lt;12 months prior to vaccination) to anti-CD20 therapy.

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 Two doses of the SARS-CoV-2 BNT162b2 vaccine enhances antibody responses to variants in individuals with prior SARS-CoV-2 infection

2021 ◽  
pp. eabj0847
Author(s):  
Richard A Urbanowicz ◽  
Theocharis Tsoleridis ◽  
Hannah J Jackson ◽  
Lola Cusin ◽  
Joshua D Duncan ◽  
...  
Keyword(s):  
Immune Responses ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Serum Samples ◽  
Igg Antibody ◽  
Enzyme Immunoassays ◽  
Antigenic Exposure ◽  
The Impact ◽  
Prior Infection

Understanding the impact of prior infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the response to vaccination is a priority for responding to the coronavirus disease 2019 (COVID-19) pandemic. In particular, it is necessary to understand how prior infection plus vaccination can modulate immune responses against variants of concern. To address this, we sampled 20 individuals with and 25 individuals without confirmed previous SARS-CoV-2 infection from a large cohort of healthcare workers followed serologically since April 2020. All 45 individuals had received two doses of the Pfizer-BioNTech BTN162b2 vaccine with a delayed booster at 10 weeks. Absolute and neutralizing antibody titers against wild-type SARS-CoV-2 and variants were measured using enzyme immunoassays and pseudotype neutralization assays. We observed antibody reactivity against lineage A, B.1.351 and P.1 variants with increasing antigenic exposure, either through vaccination or natural infection. This improvement was further confirmed in neutralization assays using fixed dilutions of serum samples. The impact of antigenic exposure was more evident in enzyme immunoassays measuring SARS-CoV-2 spike protein-specific IgG antibody concentrations. Our data show that multiple exposures to SARS-CoV-2 spike protein in the context of a delayed booster expand the neutralizing breadth of the antibody response to neutralization-resistant SARS-CoV-2 variants. This suggests that additional vaccine boosts may be beneficial in improving immune responses against future SARS-CoV-2 variants of concern.

scholarly journals SARS-CoV-2 spike protein arrested in the closed state induces potent neutralizing responses

2021 ◽  
Author(s):  
George W. Carnell ◽  
Katarzyna A. Ciazynska ◽  
David A. Wells ◽  
Xiaoli Xiong ◽  
Ernest T. Aguinam ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Protein S ◽  
Spike Protein ◽  
Receptor Binding Site ◽  
S Protein ◽  
Closed State ◽  
S Proteins ◽  
Protein Constructs

AbstractThe majority of SARS-CoV-2 vaccines in use or in advanced clinical development are based on the viral spike protein (S) as their immunogen. S is present on virions as pre-fusion trimers in which the receptor binding domain (RBD) is stochastically open or closed. Neutralizing antibodies have been described that act against both open and closed conformations. The long-term success of vaccination strategies will depend upon inducing antibodies that provide long-lasting broad immunity against evolving, circulating SARS-CoV-2 strains, while avoiding the risk of antibody dependent enhancement as observed with other Coronavirus vaccines. Here we have assessed the results of immunization in a mouse model using an S protein trimer that is arrested in the closed state to prevent exposure of the receptor binding site and therefore interaction with the receptor. We compared this with a range of other modified S protein constructs, including representatives used in current vaccines. We found that all trimeric S proteins induce a long-lived, strongly neutralizing antibody response as well as T-cell responses. Notably, the protein binding properties of sera induced by the closed spike differed from those induced by standard S protein constructs. Closed S proteins induced more potent neutralising responses than expected based on the degree to which they inhibit interactions between the RBD and ACE2. These observations suggest that closed spikes recruit different, but equally potent, virus-inhibiting immune responses than open spikes, and that this is likely to include neutralizing antibodies against conformational epitopes present in the closed conformation. Together with their improved stability and storage properties we suggest that closed spikes may be a valuable component of refined, next-generation vaccines.

scholarly journals Children develop strong and sustained cross-reactive immune responses against Spike protein following SARS-CoV-2 infection, with enhanced recognition of variants of concern

2021 ◽  
Author(s):  
Alexander C. Dowell ◽  
Megan S. Butler ◽  
Elizabeth Jinks ◽  
Gokhan Tut ◽  
Tara Lancaster ◽  
...  
Keyword(s):  
Immune Responses ◽  
Natural Infection ◽  
Humoral Response ◽  
Cellular Responses ◽  
Paediatric Population ◽  
Spike Protein ◽  
High Antibody ◽  
Antibody Titres ◽  
Clinical Protection ◽  
Th1 Cytokine

AbstractSARS-CoV-2 infection is generally mild or asymptomatic in children but the biological basis for this is unclear. We studied the profile of antibody and cellular immunity in children aged 3-11 years in comparison with adults. Antibody profiles in children were strong, with high titres against Spike protein and receptor binding domain (RBD). SARS-CoV-2 seroconversion in children strongly boosted antibody responses against seasonal beta-coronaviruses, partly through cross-recognition of the S2 domain, indicating a broad humoral response that was not seen in adults. T cell responses against Spike were also >2-fold higher in children compared to adults and displayed a strong Th1 cytokine profile. SARS-CoV-2 Spike-reactive cellular responses were present in more than half the seronegative children, indicating pre-existing cross-reactive responses or prior sensitization against SARS-CoV-2. Importantly, all children retained high antibody titres and cellular responses for more than 6 months after infection whilst relative antibody waning was seen in adults. Significantly Children at this timepoint also had high antibody titres to B1.1.7, B1.351 and P1 variants. Children thus distinctly generate robust, cross-reactive and sustained immune responses after SARS-CoV-2 infection, with focussed specificity against Spike protein. These observations demonstrate several novel features of SARS-CoV-2-specific immune responses in children and may provide insights into relative clinical protection in this group. Such information on the profile of natural infection will help to guide the introduction of vaccination regimens into the paediatric population.

scholarly journals First-in-Human Trial of a SARS CoV 2 Recombinant Spike Protein Nanoparticle Vaccine

2020 ◽  
Author(s):  
Cheryl Keech ◽  
Gary Albert ◽  
Patricia Reed ◽  
Susan Neal ◽  
Joyce S. Plested ◽  
...  
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Immune Responses ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Healthy Adults ◽  
Spike Protein ◽  
Wild Type Virus ◽  
Cell Responses ◽  
The Mean

Background NVX-CoV2373 is a recombinant nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins. We present the Day 35 primary analysis of our trial of NVX-CoV2373 with or without the saponin-based Matrix-M1 adjuvant in healthy adults. Methods This is a randomized, observer-blinded, placebo-controlled, phase 1 trial in 131 healthy adults. Trial vaccination comprised two intramuscular injections, 21 days apart. Primary outcomes were reactogenicity, safety labs, and immunoglobulin G (IgG) anti-spike protein response. Secondary outcomes included adverse events, wild-type virus neutralizing antibody, and T-cell responses. Results Participants received NVX-CoV2373 with or without Matrix-M1 (n=106) or placebo (n=25). There were no serious adverse events. Reactogenicity was mainly mild in severity and of short duration (mean ≥ 2 days), with second vaccinations inducing greater local and systemic reactogenicity. The adjuvant significantly enhanced immune responses and was antigen dose-sparing, and the two-dose 5μg NVX-CoV2373/Matrix-M1 vaccine induced mean anti-spike IgG and neutralizing antibody responses that exceeded the mean responses in convalescent sera from COVID-19 patients with clinically significant illnesses. The vaccine also induced antigen-specific T cells with a largely T helper 1 (Th1) phenotype. Conclusions NVX-CoV2373/Matrix-M1 was well tolerated and elicited robust immune responses (IgG and neutralization) four-fold higher than the mean observed in COVID-19 convalescent serum from participants with clinical symptoms requiring medical care and induced CD4+ T-cell responses biased toward a Th1 phenotype. These findings suggest that the vaccine may confer protection and support transition to efficacy evaluations to test this hypothesis. (Funded by the Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number, NCT04368988).

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