scholarly journals Full protection against all four SARS-CoV-2 variants of concern (VOC) in hamsters requires revision of spike antigen used for vaccination.

2021 ◽  
Author(s):  
Sapna Sharma ◽  
Thomas Vercruysse ◽  
Lorena Sanchez-Felipe ◽  
Winnie Kerstens ◽  
Rana Abdelnabi ◽  
...  
Keyword(s):  
First Generation ◽  
Vaccine Candidate ◽  
Marked Change ◽  
Target Antigen ◽  
Generation Vaccine ◽  
Alpha Beta ◽  
Antigenic Cartography ◽  
Protection Against Infection ◽  
Induced Immunity ◽  
Full Protection

Current licensed COVID-19 vaccines are based on antigen sequences of initial SARS-CoV-2 isolates that emerged in 2019. By mid 2021 these historical virus strains have been completely replaced by new cosmopolitan SARS-CoV-2 lineages. The ongoing pandemic has been further driven by emerging variants of concern (VOC) Alpha, Beta, Gamma and, lately predominant, Delta. These are characterized by an increased transmissibility and possible escape from naturally acquired or vaccine-induced immunity. We here show, using a YF17D-vectored first-generation COVID-19 vaccine (Sanchez-Felipe et al., 2021) and a stringent hamster challenge model (Abdelnabi et al., 2021) that the immunity elicited by a prototypic spike antigen is insufficient to provide optimal protection against the Beta VoC, urging for an antigenic update. We therefore designed an updated second-generation vaccine candidate that carries the sequence of a spike antigen that includes crucial epitopes from multiple VOCs. This vaccine candidate yielded a marked change in target antigen spectrum covered as demonstrated by (i) antigenic cartography and (ii) full protection against infection and virus-induced disease caused by any of the four VOCs (Alpha, Beta, Gamma and Delta) used for challenge. This more universal COVID-19 vaccine candidate also efficiently blocked direct transmission of VOC Delta from vaccinated infected hamsters to non-vaccinated sentinels under prolonged co-housing conditions. In conclusion, our data suggest that current first-generation COVID-19 vaccines need to be adapted to cover emerging sequence diversity of VOC to preserve vaccine efficacy and to contain virus spread at the community level.

scholarly journals Evaluation of different total Leishmania amazonensis antigens for the development of a first-generation vaccine formulated with a Toll-like receptor-3 agonist to prevent cutaneous leishmaniasis

2020 ◽  
Vol 115 ◽  
Author(s):  
María José Germanó ◽  
Esteban Sebastián Lozano ◽  
María Victoria Sanchez ◽  
Flavia Alejandra Bruna ◽  
María Fernanda García-Bustos ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
First Generation ◽  
Leishmania Amazonensis ◽  
Toll Like Receptor ◽  
Generation Vaccine

Immunogenicity and efficacy of two types of West Nile virus-like particles different in size and maturation as a second-generation vaccine candidate

Vaccine ◽  
2010 ◽  
Vol 28 (40) ◽  
pp. 6588-6596 ◽  
Author(s):  
Naohiro Ohtaki ◽  
Hidehiro Takahashi ◽  
Keiko Kaneko ◽  
Yasuyuki Gomi ◽  
Toyokazu Ishikawa ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Second Generation ◽  
Vaccine Candidate ◽  
West Nile ◽  
Virus Like Particles ◽  
Generation Vaccine

scholarly journals SARS-CoV-2 Omicron Spike recognition by plasma from individuals receiving BNT162b2 mRNA vaccination with a 16-weeks interval between doses

2021 ◽  
Author(s):  
Debashree Chatterjee ◽  
Alexandra Tauzin ◽  
Lorie Marchitto ◽  
Shang Yu Gong ◽  
Marianne Boutin ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Vaccine Efficacy ◽  
Short Interval ◽  
Antigenic Drift ◽  
Alpha Beta ◽  
Induced Immunity ◽  
Plasma Activity

Continuous emergence of SARS-CoV-2 variants of concern (VOC) is fueling the COVID-19 pandemic. Omicron (B.1.1.529), is rapidly spreading worldwide. The large number of mutations in its Spike raised concerns about a major antigenic drift that could significantly decrease vaccine efficacy and infection-induced immunity. A long interval between BNT162b2 mRNA doses was shown to elicit antibodies that efficiently recognize Spikes from different VOCs. Here we evaluated the recognition of Omicron Spike by plasma from a cohort of SARS-CoV-2 naive and previously-infected individuals that received their BNT162b2 mRNA vaccine 16-weeks apart. Omicron Spike was recognized less efficiently than D614G, Alpha, Beta, Gamma and Delta Spikes. We compared to plasma activity from participants receiving a short (4-weeks) interval regimen. Plasma from individuals of the long interval cohort neutralized better the Omicron Spike compared to those that received a short interval. Whether this difference confers any clinical benefit against Omicron remains unknown.

scholarly journals Analytical evaluation and critical appraisal of early commercial SARS-CoV-2 immunoassays for routine use in a diagnostic laboratory

2020 ◽  
Author(s):  
Amanda Cramer ◽  
Nigel Goodman ◽  
Timothy Cross ◽  
Vanya Gant ◽  
Magdalena Dziadzio
Keyword(s):  
First Generation ◽  
Diagnostic Yield ◽  
Point Of Care ◽  
Serum Samples ◽  
Diagnostic Laboratory ◽  
Flow Device ◽  
Antibody Assays ◽  
Asymptomatic Subjects ◽  
Induced Immunity ◽  
Selection Of

AbstractBACKGROUNDThe objective of this study was to evaluate the performance characteristics of early commercial SARS-CoV-2 antibody assays in mild and asymptomatic subjects to enable the selection of suitable serological assays for routine diagnostic use within HCA Healthcare UK.METHODSWe used serum samples from a pre-Covid era patient cohort (n=50, pre-December 2019), designated SARS-CoV-2 negative, and serum samples from a SARS-CoV-2 RT-PCR-positive cohort (n=90) taken > 14 days post symptom onset (April-May 2020). We evaluated 6 ELISA assays including one confirmation assay to investigate antibody specificity. We also evaluated one point-of-care lateral flow device and one high throughput electrochemiluminescence immunoassay.RESULTSThe ELISA specificities ranged from 84-100%, with sensitivities ranging from 75.3-90.0%. The LFIA showed 100% specificity and 80% sensitivity using smaller sample numbers. The Roche CLIA immunoassay showed 100% specificity and 90.7% sensitivity. When used in conjunction, the Euroimmun nucleocapsid (NC) and spike-1 (S1) IgG ELISA assays had a sensitivity of 95.6%. The confirmation IgG assay showed 92.6% of samples tested contained both NC and S1 antibodies, 32.7% had NC, S1 and S2 and 0% had either S1 or S2 only.CONCLUSIONSThese first generation assays were not calibrated against reference material and the results are reported qualitatively. The Roche assay and the Euroimmun NC and S1 assays had the best sensitivity overall in our hands. Combining the assays detecting NC and S1/S2 antibody increased diagnostic yield. A portfolio of next generation SARS-CoV-2 immunoassays will be necessary in any future studies of herd and vaccine induced immunity.

scholarly journals The glycoprotein Ib-IX complex-specific monoclonal antibody SZ1 binds to a conformation-sensitive epitope on glycoprotein IX: implications for the target antigen of quinine/quinidine-dependent autoantibodies

Blood ◽  
1995 ◽  
Vol 85 (5) ◽  
pp. 1254-1258 ◽  
Author(s):  
JA Lopez ◽  
CQ Li ◽  
S Weisman ◽  
M Chambers
Keyword(s):  
Monoclonal Antibody ◽  
Complex Formation ◽  
Beta Cells ◽  
Cell Lines ◽  
Target Antigen ◽  
Specific Monoclonal Antibody ◽  
Glycoprotein Ib ◽  
Transfected Cells ◽  
Alpha Beta

The monoclonal antibody SZ1 is of interest for two reasons: it was used to define complex formation between glycoprotein (GP) Ib and GP IX, and its epitope is likely to be identical to that recognized by most quinine- and quinidine-dependent autoantibodies that cause thrombocytopenia. To determine the location of the epitope for SZ1 within the GP Ib-IX complex (which consists of three subunits: GP Ib alpha, GP Ib beta, and GP IX), we tested the ability of the antibody to bind transfected cells that expressed different combinations of complex subunits, and compared this binding to the binding of antibodies of known specificity. SZ1 bound to cells that expressed the entire GP Ib- IX complex in the same pattern as did AN51 (an antibody specific for GP Ib alpha). However, unlike AN51, SZ1 did not bind alpha beta cells (ie, cells that express GP Ib alpha and GP Ib beta, but not GP IX), but did bind to beta IX and alpha IX cells. We then compared the binding patterns of SZ1 and FMC25, an antibody specific for GP IX. Both bound virtually identically to cell lines that expressed every combination of two of the three GP Ib-IX complex subunits. However, the epitopes of the two antibodies were not identical, because fixation with 4% paraformaldehyde of cells that expressed GP IX destroyed the SZ1 epitope while maintaining the FMC25 epitope. Because of the ability of SZ1 to block the binding of many quinine- and quinidine-dependent antibodies, these data strongly suggest that GP IX is the component of the GP Ib-IX complex recognized by those antibodies.

scholarly journals Construction and Evaluation of a Safe, Live, Oral Vibrio cholerae Vaccine Candidate, IEM108

2003 ◽  
Vol 71 (10) ◽  
pp. 5498-5504 ◽  
Author(s):  
Weili Liang ◽  
Shixia Wang ◽  
Fenggang Yu ◽  
Lijuan Zhang ◽  
Guoming Qi ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Protective Antigen ◽  
Vaccine Candidate ◽  
Rabbit Model ◽  
Housekeeping Gene ◽  
Cholera Vaccine ◽  
Oral Cholera Vaccine ◽  
Toxigenic Strains ◽  
El Tor ◽  
Full Protection

ABSTRACT IEM101, a Vibrio cholerae O1 El Tor Ogawa strain naturally deficient in CTXΦ, was previously selected as a live cholera vaccine candidate. To make a better and safer vaccine that can induce protective immunity against both the bacteria and cholera toxin (CT), a new vaccine candidate, IEM108, was constructed by introducing a ctxB gene and an El Tor-derived rstR gene into IEM101. The ctxB gene codes for the protective antigen CTB subunit, and the rstR gene mediates phage immunity. The stable expression of the two genes was managed by a chromosome-plasmid lethal balanced system based on the housekeeping gene thyA. Immunization studies indicate that IEM108 generates good immune responses against both the bacteria and CT. After a single-dose intraintestinal vaccination with 109 CFU of IEM108, both anti-CTB immunoglobulin G and vibriocidal antibodies were detected in the immunized-rabbit sera. However, only vibriocidal antibodies are detected in rabbits immunized with IEM101. In addition, IEM108 but not IEM101 conferred full protection against the challenges of four wild-type toxigenic strains of V. cholerae O1 and 4 μg of CT protein in a rabbit model. By introducing the rstR gene, the frequency of conjugative transfer of a recombinant El Tor-derived RS2 suicidal plasmid to IEM108 was decreased 100-fold compared to that for IEM101. This indicated that the El Tor-derived rstR cloned in IEM108 was fully functional and could effectively inhibit the El Tor-derived CTXΦ from infecting IEM108. Our results demonstrate that IEM108 is an efficient and safe live oral cholera vaccine candidate that induces antibacterial and antitoxic immunity and CTXΦ phage immunity.

scholarly journals Measuring vaccine efficacy against infection and disease in clinical trials: sources and magnitude of bias in COVID-19 vaccine efficacy estimates

2021 ◽  
Author(s):  
Lucy R. Williams ◽  
Neil M. Ferguson ◽  
Christl A. Donnelly ◽  
Nicholas C. Grassly
Keyword(s):  
Vaccine Efficacy ◽  
Asymptomatic Infection ◽  
Phase Iii ◽  
Uncertainty Interval ◽  
Considerable Uncertainty ◽  
Study Results ◽  
Phase Iii Trials ◽  
Asymptomatic Infections ◽  
Protection Against Infection ◽  
Induced Immunity

Background Phase III trials have estimated COVID-19 vaccine efficacy (VE) against symptomatic and asymptomatic infection. We explore the direction and magnitude of potential biases in these estimates and their implications for vaccine protection against infection and against disease in breakthrough infections. Methods We developed a mathematical model that accounts for natural and vaccine-induced immunity, changes in serostatus and imperfect sensitivity and specificity of tests for infection and antibodies. We estimated expected biases in VE against symptomatic, asymptomatic and any SARS-CoV-2 infections and against disease following infection for a range of vaccine characteristics and measurement approaches, and the likely overall biases for published trial results that included asymptomatic infections. Results VE against asymptomatic infection measured by PCR or serology is expected to be low or negative for vaccines that prevent disease but not infection. VE against any infection is overestimated when asymptomatic infections are less likely to be detected than symptomatic infections and the vaccine protects against symptom development. A competing bias towards underestimation arises for estimates based on tests with imperfect specificity, especially when testing is performed frequently. Our model indicates considerable uncertainty in Oxford-AstraZeneca ChAdOx1 and Janssen Ad26.COV2.S VE against any infection, with slightly higher than published, bias-adjusted values of 59.0% (95% uncertainty interval [UI] 38.4 to 77.1) and 70.9% (95% UI 49.8 to 80.7) respectively. Conclusion Multiple biases are likely to influence COVID-19 VE estimates, potentially explaining the observed difference between ChAdOx1 and Ad26.COV2.S vaccines. These biases should be considered when interpreting both efficacy and effectiveness study results.

scholarly journals SARS-Cov-2 Infection versus Vaccine-Induced Immunity among Veterans

2021 ◽  
Author(s):  
Yinong Young-Xu ◽  
Jeremy Smith ◽  
Caroline Korves
Keyword(s):  
Young Adults ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards Model ◽  
Natural Immunity ◽  
Veterans Health ◽  
Health Administration ◽  
The Us ◽  
Previous Infection ◽  
Protection Against Infection ◽  
Induced Immunity

Background: With over 40 million cases of SARS-CoV-2 infection reported in the US and discussion of both vaccine mandates as well as boosters ongoing, we aim to examine protection conferred by previous infection compared with vaccination so that citizens and policy makers can make informed decisions. Objectives: To compare mRNA COVID-19 vaccine-induced immunity against immunity induced by previous infection with SARS-CoV-2 between June and August 2021 when the Delta variant became dominant in the US. We conducted a retrospective observational study comparing two groups whose incident vaccination or infection occurred within the first two months of 2021: (1) SARS-CoV-2-naive individuals who received a full mRNA vaccination - 2 doses of either Pfizer or Moderna vaccine, (2) newly infected individuals who were subdivided into those have not been vaccinated and those have been vaccinated after their infection. Matched multivariable Cox proportional hazards model was applied. We evaluated laboratory (RT-PCR) confirmed SARS-CoV-2 infection during follow-up, COVID-related hospitalization, and deaths. Setting: Veterans Health Administration (VHA). Main outcomes: Positive SARS-CoV-2 PCR test, COVID-related hospitalization, and deaths. Protection was estimated from hazard ratios with 95% confidence intervals (CI). Results: A total of 9,539 patients with SARS-CoV-2 infection during the first two months of 2021 were matched to 14,458 and 23,105 patients fully vaccinated with Moderna and Pfizer mRNA vaccines, during the same two months. 3,917 (41%) of patients with SARS-CoV-2 infection were subsequently vaccinated. We plan to study this group separately. Consequently, protections were estimated among those with infection but were not subsequently vaccinated and those vaccinated with a mRNA vaccine. Among seniors, Moderna and Pfizer mRNA vaccines offered stronger protection against infection, lowering the risk by an additional 66% [HR: 0.34 (95% CI, 0.14-0.78)] and 68% [HR: 0.32 (95% CI, 0.14-0.70)]; stronger protection against hospitalization, lowering the risk by an additional 61% [HR: 0.34 (95% CI, 0.14-0.78)] and 45% [HR: 0.34 (95% CI, 0.14-0.78)]; and stronger protection against deaths lowering the risk by an additional 95% [HR: 0.05 (95% CI, 0.004-0.62)] and 99% [HR: 0.01 (95% CI, 0.001-0.44)]. Among young adults (age < 65), the protections offered by vaccines were statistically equivalent to that provided by previous infection, especially in terms of absolute incidence rate. Conclusions Among the elderly (age 65 or older), two-dose mRNA vaccines provided stronger protection against infection, hospitalization, and death, compared to natural immunity. Among young adults (age < 65), the protections offered between natural immunity and vaccine-induced immunity were similar.

scholarly journals Building momentum for malaria vaccine research and development: key considerations

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Chetan E. Chitnis ◽  
David Schellenberg ◽  
Johan Vekemans ◽  
Edwin J. Asturias ◽  
Philip Bejon ◽  
...  
Keyword(s):  
Research And Development ◽  
Malaria Control ◽  
First Generation ◽  
Malaria Vaccine ◽  
Next Generation ◽  
Vaccine Research ◽  
Medium Term ◽  
Vaccine Candidates ◽  
Malaria Vaccines ◽  
Generation Vaccine

AbstractTo maintain momentum towards improved malaria control and elimination, a vaccine would be a key addition to the intervention toolkit. Two approaches are recommended: (1) promote the development and short to medium term deployment of first generation vaccine candidates and (2) support innovation and discovery to identify and develop highly effective, long-lasting and affordable next generation malaria vaccines.

Sign in / Sign up

Export Citation Format

Share Document