scholarly journals Mucosal and systemic responses to SARS-CoV-2 vaccination in infection naive and experienced individuals

2021 ◽  
Author(s):  
Mohammad M. Sajadi ◽  
Amber Myers ◽  
James Logue ◽  
Saman Saadat ◽  
Narjes Shokatpour ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Cellular Responses ◽  
Post Vaccination ◽  
Recall Response ◽  
S Protein ◽  
Time Points ◽  
The World ◽  
Cd4 Cell ◽  
Systemic Responses

With much of the world infected with or vaccinated against SARS-CoV-2, understanding the immune responses to the SARS-CoV-2 spike (S) protein in different situations is crucial to controlling the pandemic. We studied the clinical, systemic, mucosal, and cellular responses to two doses of SARS-CoV-2 mRNA vaccines in 62 individuals with and without prior SARS-CoV-2 exposure that were divided into three groups based on serostatus and/or degree of symptoms: Antibody negative, Asymptomatic, and Symptomatic. In the previously SARS-CoV-2-infected (SARS2-infected) Asymptomatic and Symptomatic groups, symptoms related to a recall response were elicited after the first vaccination. Anti-S trimer IgA and IgG levels peaked after 1st vaccination in the SARS2-infected groups, and were higher that the in the SARS2-naive group in the plasma and nasal samples at all time points. Neutralizing antibodies titers were also higher against the WA-1 and B.1.617.2 (Delta) variants of SARS-CoV-2 in the SARS2-infected compared to SARS2-naive vaccinees. After the first vaccination, differences in cellular immunity were not evident between groups, but the AIM+ CD4+ cell response correlated with durability of humoral immunity against the SARS-CoV-2 S protein. In those SARS2-infected, the number of vaccinations needed for protection, the durability, and need for boosters are unknown. However, the lingering differences between the SARS2-infected and SARS2-naive up to 10 months post-vaccination could explain the decreased reinfection rates in the SARS2-infected vaccinees recently reported and suggests that additional strategies (such as boosting of the SARS2-naive vaccinees) are needed to narrow the differences observed between these groups.

scholarly journals The vaccinia-based Sementis Copenhagen Vector COVID-19 vaccine induces broad and durable cellular and humoral immune responses

2021 ◽  
Author(s):  
Preethi Eldi ◽  
Tamara H Cooper ◽  
Natalie A Prow ◽  
Liang Liu ◽  
Gary K Heinemann ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
First Generation ◽  
Neutralizing Antibody ◽  
Immune Memory ◽  
Antibody Activity ◽  
Post Vaccination ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Heterologous Boost

The ongoing COVID-19 pandemic perpetuated by SARS-CoV-2 variants, has highlighted the continued need for broadly protective vaccines that elicit robust and durable protection. Here, the vaccinia virus-based, replication-defective Sementis Copenhagen Vector (SCV) was used to develop a first-generation COVID-19 vaccine encoding the spike glycoprotein (SCV-S). Vaccination of mice rapidly induced polyfunctional CD8 T cells with cytotoxic activity and robust Th1-biased, spike-specific neutralizing antibodies, which are significantly increased following a second vaccination, and contained neutralizing activity against the alpha and beta variants of concern. Longitudinal studies indicated neutralizing antibody activity was maintained up to 9 months post-vaccination in both young and aging mice, with durable immune memory evident even in the presence of pre-existing vector immunity. This immunogenicity profile suggests a potential to expand protection generated by current vaccines in a heterologous boost format, and presents a solid basis for second-generation SCV-based COVID-19 vaccine candidates incorporating additional SARS-CoV-2 immunogens.

scholarly journals Evaluation of Cellular Immune Responses in Dogs Immunized with Alum-Precipitated Autoclaved Leishmania major along with BCG and Imiquimod

2021 ◽  
Author(s):  
Mohammad Barati ◽  
Mehdi Mohebali ◽  
Ali Khamesipour ◽  
Fariborz Bahrami ◽  
Haiedeh Darabi ◽  
...  
Keyword(s):  
Immune Responses ◽  
Leishmania Major ◽  
Delayed Type Hypersensitivity ◽  
Post Vaccination ◽  
Time Points ◽  
Measurement Results ◽  
Ifn Γ ◽  
Pre Treatment ◽  
Th1 And Th2 Responses ◽  
Cellular Immune

Background: We aimed to investigate the potential effects of BCG and imiquimod on improvement of current experimental L. major vaccine against dogs in an endemic area of Zoonotic visceral leishmaniasis (ZVL) in Iran. Methods: During 2012 till 2014, seven mixedbreed shepherd dogs with no anti-Leishmania antibodies and no response to Leishmanin reagent were immunized with 2 doses of alum-precipitated autoclaved L. major (Alum-AML) while BCG and imiquimod (for skin pre-treatment) were used as adjuvants. The productions of a few characteristic cytokines of T-helper immune responses and the development of delayed-type hypersensitivity (DTH) of the immunized animals were then evaluated, up to 300 days. Blood samples were collected at 0, 30, 80 and 300 d post-vaccination and the concentrations of IFN-γ, IL10, IL-12 and TGF-β cytokines secreted from PBMCs at these time-points were quantified by ELISA. DTH was evaluated by Leishmanin skin test (LST). Results: Although a similar LST conversion was observed at all time-points, the cytokine measurement results indicated significantly higher levels of IFN-γ at day 80 and elevated levels of IL-10 at days 80 and 300, post-vaccination. Moreover, a significantly higher IFN-γ/IL-10 ratio was observed at day 30 post-vaccination compared to the other time-points. Conclusion: Although a Th1-like response could be observed at day 30 post-vaccination, the development of cytokine profiles was inclined toward mixed Th1 and Th2 responses at days 80 and 300 post-vaccination. This situation may indicate the requirement of an additional boosting by this Alum-AML formula, in order to induce long-lasting protection against ZVL.

scholarly journals The Emergence and Spread of Novel SARS-CoV-2 Variants

2021 ◽  
Vol 9 ◽  
Author(s):  
Huaimin Yi ◽  
Jin Wang ◽  
Jiong Wang ◽  
Yuying Lu ◽  
Yali Zhang ◽  
...  
Keyword(s):  
Immune Response ◽  
Severe Acute Respiratory Syndrome ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Neutralizing Antibodies ◽  
Whole Genome ◽  
Distribution Characteristics ◽  
S Protein ◽  
The World ◽  
Viral Genes

Since severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) began to spread in late 2019, laboratories around the world have widely used whole genome sequencing (WGS) to continuously monitor the changes in the viral genes and discovered multiple subtypes or branches evolved from SARS-CoV-2. Recently, several novel SARS-CoV-2 variants have been found to be more transmissible. They may affect the immune response caused by vaccines and natural infections and reduce the sensitivity to neutralizing antibodies. We analyze the distribution characteristics of prevalent SARS-CoV-2 variants and the frequency of mutant sites based on the data available from GISAID and PANGO by R 4.0.2 and ArcGIS 10.2. Our analysis suggests that B.1.1.7, B.1.351, and P.1 are more easily spreading than other variants, and the key mutations of S protein, including N501Y, E484K, and K417N/T, have high mutant frequencies, which may have become the main genotypes for the spread of SARS-CoV-2.

scholarly journals Landscape analysis of escape variants identifies SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization

2020 ◽  
Author(s):  
Zhuoming Liu ◽  
Laura A. VanBlargan ◽  
Paul W. Rothlauf ◽  
Louis-Marie Bloyet ◽  
Rita E. Chen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Serum Antibody ◽  
Single Amino Acid ◽  
Cross Resistance ◽  
S Protein ◽  
Mutational Landscape ◽  
Immune Mediated ◽  
Human Sera ◽  
Escape Mutants

ABSTRACTAlthough neutralizing antibodies against the SARS-CoV-2 spike (S) protein are a goal of most COVID-19 vaccines and being developed as therapeutics, escape mutations could compromise such countermeasures. To define the immune-mediated mutational landscape in S protein, we used a VSV-eGFP-SARS-CoV-2-S chimeric virus and 19 neutralizing monoclonal antibodies (mAbs) against the receptor binding domain (RBD) to generate 48 escape mutants. These variants were mapped onto the RBD structure and evaluated for cross-resistance by convalescent human plasma. Although each mAb had unique resistance profiles, many shared residues within an epitope, as several variants were resistant to multiple mAbs. Remarkably, we identified mutants that escaped neutralization by convalescent human sera, suggesting that some humans induce a narrow repertoire of neutralizing antibodies. By comparing the antibody-mediated mutational landscape in S protein with sequence variation in circulating SARS-CoV-2 strains, we identified single amino acid substitutions that could attenuate neutralizing immune responses in some humans.

scholarly journals 578. INO-4800 DNA Vaccine Induces Neutralizing Antibodies and T cell Activity Against Global SARS-CoV-2 Variants

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S390-S391
Author(s):  
Viviane M Andrade ◽  
Aaron Christensen-Quick ◽  
Joseph Agnes ◽  
Jared Tur ◽  
Charles C Reed ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Dna Vaccine ◽  
Stock Options ◽  
Neutralizing Antibodies ◽  
Cell Activity ◽  
Cellular Responses ◽  
Neutralization Assay ◽  
Material Support ◽  
Fold Reduction

Abstract Background Global surveillance has identified emerging SARS-CoV-2 variants of concern (VOC) associated with increased transmissibility, disease severity, and resistance to neutralization by current vaccines under emergency use authorization (EUA). Here we assessed cross-immune responses of INO-4800 vaccinated subjects against SARS-CoV-2 VOCs. Methods We used a SARS-CoV-2 IgG ELISA and a pseudo neutralization assay to assess humoral responses, and an IFNγ ELISpot to measure cellular responses against SARS-CoV-2 VOC in subjects immunized with the DNA vaccine, INO-4800. Results IgG binding titers were not impacted between wild-type (WT) and B.1.1.7 or B.1.351 variants. An average 1.9-fold reduction was observed for the P.1 variant in subjects tested at week 8 after receiving two doses of INO-4800 (Figure 1a). We performed a SARS-CoV-2 pseudovirus neutralization assay using sera collected from 13 subjects two weeks after administration of a third dose of either 0.5 mg, 1 mg, or 2 mg of INO-4800. Neutralization was detected against WT and the emerging variants in all samples tested. The mean ID50 titers for the WT, B.1.1.7, B.1.351 and P.1. were 643 (range: 70-729), 295 (range: 46-886), 105 (range: 25-309), and 664 (range: 25-2087), respectively. Compared to WT, there was a 2.1 and 6.9-fold reduction for B.1.1.7 and B.1.351, respectively, while there was no difference between WT and the P.1 variant (Figure 1b). Next, we compared cellular immune responses to WT and SARS-CoV-2 Spike variants elicited by INO-4800 vaccination. We observed similar cellular responses to WT (median = 82.2 IQR = 58.9-205.3), B.1.1.7 (79.4, IQR = 38.9- 179.7), B.1.351 (80, IQR = 40.0-208.6) and P.1 (78.3, IQR = 53.1-177.8) Spike peptides (Figure 2). Conclusion INO-4800 vaccination induced neutralizing antibodies against all variants tested, with reduced levels detected against B.1.351. IFNγ T cell responses were fully maintained against all variants tested. Disclosures Viviane M. Andrade, PhD, Inovio Pharmaceuticals Inc. (Employee) Aaron Christensen-Quick, PhD, Inovio Pharmaceuticals, Inc (Employee) Joseph Agnes, PhD, Inovio (Employee, Shareholder) Jared Tur, PhD, Inovio (Employee) Charles C. Reed, PhD, Inovio Pharmaceuticals (Employee, Shareholder) Richa Kalia, MS, Inovio Pharmaceuticals (Employee, Other Financial or Material Support, I have stock options with Inovio Pharmaceuticals as an employee.) Idania Marrero, MD, PhD, Inovio Pharmaceuticals (Employee, Shareholder) Dustin Elwood, PhD, Inovio Pharmaceuticals (Employee) Katherine Schultheis, MSc, Inovio Pharmaceuticals (Employee) Emma Reuschel, PhD, Inovio Pharmaceuticals (Employee) Trevor McMullan, MSc, Inovio (Shareholder) Patrick Pezzoli, BS, Inovio (Employee) Kimberly A. Kraynyak, PhD, Inovio Pharmaceuticals (Employee, Other Financial or Material Support, Stock options) Albert Sylvester, MS, Inovio (Employee, Shareholder) Mammen P. Mammen Jr., MD, Inovio Pharmaceuticals (Employee) J Joseph Kim, PhD, Inovio (Employee) David Weiner, PhD, Inovio (Board Member, Grant/Research Support, Shareholder, I serve on the SAB in addition to the above activities) Trevor R. F. Smith, PhD, Inovio (Employee, Shareholder) Stephanie Ramos, PhD, Inovio Pharmaceuticals (Employee) Laurent Humeau, PhD, Inovio Pharmaceuticals (Employee) Jean Boyer, PhD, Inovio (Employee) Kate Broderick, PhD, Inovio (Employee)

scholarly journals Immunogenicity of low dose prime-boost vaccination of mRNA vaccine CV07050101 in non-human primates

2021 ◽  
Author(s):  
Neeltje van Doremalen ◽  
Robert Fischer ◽  
Jonathan Schulz ◽  
Myndi Holbrook ◽  
Brian Smith ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Vaccine Candidate ◽  
Small Animal ◽  
S Protein ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Boost Vaccination ◽  
Human Volunteers ◽  
Cellular Immune

Many different vaccine candidates against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiological agent of COVID-19, are currently approved and under development. Vaccine platforms vary from mRNA vaccines to viral-vectored vaccines, and several candidates have been shown to produce humoral and cellular responses in small animal models, non-human primates and human volunteers. In this study, six non-human primates received a prime-boost intramuscular vaccination with 4 μg of mRNA vaccine candidate CV07050101, which encodes a pre-fusion stabilized spike (S) protein of SARS-CoV-2. Boost vaccination was performed 28 days post prime vaccination. As a control, six animals were similarly injected with PBS. Humoral and cellular immune responses were investigated at time of vaccination, and two weeks afterwards. No antibodies could be detected two and four weeks after prime vaccination. Two weeks after boost vaccination, binding but no neutralizing antibodies were detected in 4 out of 6 non-human primates. SARS-CoV-2 S protein specific T cell responses were detected in these 4 animals. In conclusion, prime-boost vaccination with 4 μg of vaccine candidate CV07050101 resulted in limited immune responses in 4 out of 6 non-human primates.

scholarly journals High seroconversion rate and SARS-CoV-2 Delta neutralization in PLWHIV vaccinated with BNT162b2

2021 ◽  
Author(s):  
Valérie Pourcher ◽  
Lisa Belin ◽  
Cathia Soulie ◽  
Michelle Rosenzwajg ◽  
Stéphane Marot ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralization Test ◽  
Seroconversion Rate ◽  
Cellular Responses ◽  
Vaccination Schedule ◽  
Igg Antibodies ◽  
Multicenter Cohort Study ◽  
Cd4 Cell Count ◽  
Neutralization Capacity ◽  
Cd4 Cell

AbstractObjectivesTo assess the humoral and cellular responses against SARS-CoV-2 Delta variant after BNT162b2 vaccination in PLWHIV.DesignMulticenter cohort study of PLWHIV, with a CD4 cell count <500/mm3 and a viral load <50 copies/ml on stable antiretroviral therapy for at least 3 months.MethodsAnti-SARS-CoV-2 Receptor Binding Domain IgG antibodies (anti-RBD IgG) were quantified and their neutralization capacity was evaluated using an ELISA (GenScript) and a virus neutralization test (VNT), against historical strain, Beta and Delta variants before vaccination (day 0) and one month after a complete vaccination schedule (M1).Results97 patients were enrolled in the study: 85 received 2 vaccine doses (11 previous COVID-19 and 1 premature exit). The seroconversion rate in anti-RBD IgG was 97% CI95[90%; 100%] at M1. Median (IQR) anti-RBD IgG titer was 0.97 (0.97-5.3) BAU/ml at D0 and 1219 (602-1929) at M1. Neutralizing antibodies (NAbs) capacity improved between D0 (15% CI95[8%; 23%]) and M1 (94% CI95[87%; 98%]) with the GenScript assay (p<0.0001). At M1, NAbs against historical strain, Beta and Delta variants were present in 82%, 77% and 84% patients respectively. The seroconversion rate and median anti-RBD IgG were 91% and 852 BAU/ml in patients with CD4<250/mm3 (n=13) and 98% and 1270 BAU/ml in patients with CD4>250/mm3 (n=64) (p=0.3994). 73% of patients with CD4<250 had NAbs and 97% of those with CD4>250 (p=0.0130). The NAbs against Beta variant was elicited in 50% in CD4<250 and in 81% in CD4>250 (p=0.0292). No change in CD4+ or CD8+ T cells count was observed while a decrease of CD19+ B cells count was observed (208 ±124 cells/mm3 at D0 vs 188 ±112 cells/mm3 at M1, p<0.01). No notable adverse effects or COVID-19 were reported.ConclusionsThese results show a high seroconversion rate with a Delta neutralization in PLWHIV patients after a complete BNT162b2 vaccination schedule.

scholarly journals Phase 1 Assessment of the Safety and Immunogenicity of an mRNA- Lipid Nanoparticle Vaccine Candidate Against SARS-CoV-2 in Human Volunteers

2020 ◽  
Author(s):  
Peter Kremsner ◽  
Philipp Mann ◽  
Jacobus Bosch ◽  
Rolf Fendel ◽  
Julian J. Gabor ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Clinical Investigation ◽  
Phase 1 ◽  
Fold Increase ◽  
Serious Adverse Events ◽  
S Protein ◽  
Human Volunteers ◽  
Dose Dependent

ABSTRACTThere is an urgent need for vaccines to counter the COVID-19 pandemic due to infections with severe acute respiratory syndrome coronavirus (SARS-CoV-2). Evidence from convalescent sera and preclinical studies has identified the viral Spike (S) protein as a key antigenic target for protective immune responses. We have applied an mRNA-based technology platform, RNActive®, to develop CVnCoV which contains sequence optimized mRNA coding for a stabilized form of S protein encapsulated in lipid nanoparticles (LNP). Following demonstration of protective immune responses against SARS-CoV-2 in animal models we performed a dose-escalation phase 1 study in healthy 18-60 year-old volunteers.This interim analysis shows that two doses of CVnCoV ranging from 2 μg to 12 μg per dose, administered 28 days apart were safe. No vaccine-related serious adverse events were reported. There were dose-dependent increases in frequency and severity of solicited systemic adverse events, and to a lesser extent of local reactions, but the majority were mild or moderate and transient in duration. Immune responses when measured as IgG antibodies against S protein or its receptor-binding domain (RBD) by ELISA, and SARS-CoV-2-virus neutralizing antibodies measured by micro-neutralization, displayed dose-dependent increases. Median titers measured in these assays two weeks after the second 12 μg dose were comparable to the median titers observed in convalescent sera from COVID-19 patients. Seroconversion (defined as a 4-fold increase over baseline titer) of virus neutralizing antibodies two weeks after the second vaccination occurred in all participants who received 12 μg doses.Preliminary results in the subset of subjects who were enrolled with known SARS-CoV-2 seropositivity at baseline show that CVnCoV is also safe and well tolerated in this population, and is able to boost the pre-existing immune response even at low dose levels.Based on these results, the 12 μg dose is selected for further clinical investigation, including a phase 2b/3 study that will investigate the efficacy, safety, and immunogenicity of the candidate vaccine CVnCoV.

scholarly journals Immune response to COVID-19 vaccination is attenuated by poor disease control and antimyeloma therapy with vaccine driven divergent T cell response

2021 ◽  
Author(s):  
Karthik Ramasamy ◽  
Ross Sadler ◽  
Sally Jeans ◽  
Paul Weeden ◽  
Sherin Varghese ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Cellular Responses ◽  
Male Gender ◽  
T Cell Response ◽  
S Protein ◽  
Therapy Regimen ◽  
Humoral Immune ◽  
The Uk ◽  
A Prospective Study

Background: Myeloma patients frequently respond poorly to bacterial and viral vaccination. Small number of studies have reported poor humoral immune responses in myeloma patients to COVID-19 vaccination. Methods: Using a prospective study of a myeloma and smouldering myeloma patients within the UK rudystudy cohort, we assessed humoral and cellular immune responses to COVID-19 vaccination post second COVID-19 vaccine administration. Findings: We report data from 214 adults with myeloma (n=204) or smouldering myeloma (n=10) who provided blood samples at least 3 weeks after second vaccine dose.Positive Anti-S antibody levels (> 50 IU/ml) were detected in 188/203 (92.5%), positive IGRA responses were seen in 102/167 (61.7%). Only 9/167 patients were identified to have both a negative IGRA and negative Anti-S protein antibody response. 100/167 (59.8%) patients produced positive results for both S protein serology and IGRA. After adjusting for disease severity and myeloma therapy, poor humoral immune response was predicted by male gender. Predictors of poor IGRA included antiCD38/ BCMA therapy and Pfizer-BioNTech vaccination.. Interpretation: A significant majority of myeloma patients elicit Anti-S protein antibody responses to COVID-19 vaccine with approximately half of myeloma patients show both positive COVID serology, and cellular responses via IGRA. Predictors of a poor immune response included male gender, myeloma therapy regimen and vaccination with Pfizer-BioNTech vaccination. Further work is needed to understand the clinical significance of patients discordant for humoral and cellular responses.

scholarly journals Immunogenicity of Low-Dose Prime-Boost Vaccination of mRNA Vaccine CV07050101 in Non-Human Primates

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1645
Author(s):  
Neeltje van Doremalen ◽  
Robert J. Fischer ◽  
Jonathan E. Schulz ◽  
Myndi G. Holbrook ◽  
Brian J. Smith ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Vaccine Candidate ◽  
Small Animal ◽  
S Protein ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Boost Vaccination ◽  
Human Volunteers ◽  
Cellular Immune

Many different vaccine candidates against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, are currently approved and under development. Vaccine platforms vary from mRNA vaccines to viral-vectored vaccines, and several candidates have been shown to produce humoral and cellular responses in small animal models, non-human primates, and human volunteers. In this study, six non-human primates received a prime-boost intramuscular vaccination with 4 µg of mRNA vaccine candidate CV07050101, which encodes a pre-fusion stabilized spike (S) protein of SARS-CoV-2. Boost vaccination was performed 28 days post prime vaccination. As a control, six animals were similarly injected with PBS. Humoral and cellular immune responses were investigated at time of vaccination, and two weeks afterwards. No antibodies could be detected at two and four weeks after prime vaccination. Two weeks after boost vaccination, binding but no neutralizing antibodies were detected in four out of six non-human primates. SARS-CoV-2 S protein-specific T cell responses were detected in these four animals. In conclusion, prime-boost vaccination with 4 µg of vaccine candidate CV07050101 resulted in limited immune responses in four out of six non-human primates.

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