In Vitro Clonal Priming Data Suggests Mechanism for Lower Initial Vaccine Dose Yielding Increased Immunity in Astra-Zeneca Vaccine Trial

2021 ◽  
Vol 20 (4) ◽  
pp. 483-484
Author(s):  
Alan Dattner ◽  
Frank Martiniuk ◽  
William Levis
Keyword(s):  
Vaccine Trial ◽  
Vaccine Dose

scholarly journals Application of Median Lethal Concentration (LC50) of Pathogenic Microorganisms and Their Antigens in Vaccine Development

2020 ◽  
Author(s):  
Saganuwan Alhaji Saganuwan
Keyword(s):  
Staphylococcus Aureus ◽  
Disease Virus ◽  
Vaccine Development ◽  
Hepatitis A Virus ◽  
Lethal Dose ◽  
Vaccine Dose ◽  
Foot And Mouth Disease ◽  
Bacterial Colony ◽  
Mouth Disease Virus

Abstract Objective: Lack of ideal mathematical models to qualify and quantify both pathogenicity, and virulence is a dreadful setback in development of new antimicrobials and vaccines against resistance pathogenic microorganisms.Hence, the modified arithmetical formula of Reed and Muenchhas been integrated with other formulas and used to determine bacterial colony forming unit/ viral concentration, virulence and immunogenicity from LC50s established in the laboratories. Results: Microorganisms’antigens tested are Staphylococcus aureus, Streptococcuspneumonia, Pseudomonas aeruginosa in mice and rat, Edwardsiellaictaluri, Aeromonashydrophila, Aeromonasveronii in fish, New Castle Disease virus in chicken, Sheep Pox Virus, Foot-and-Mouth Disease Virus and Hepatitis A virus in vitro, respectively. The LC50s for the pathogens using different routes of administrations are 1.93 x 103(sheep poxvirus) and 1.75 x 1010 for Staphylococcus aureus (ATCC29213) in rat respectively. Titre index (TI) equals N log10 LC50 and provides protection against lethal dose in graded fashion which translates to protection index. N is the number of vaccine dose that could neutralize the LC50. Hence, parasite inoculum of 103 to 1011could be used as basis for determination of median lethal dose(LD50), LC50 and median bacterial concentrations (BC50)determination, pathogenic dose for immune stimulation should be sought at concentrations less than LC10.

scholarly journals Determination of Median Lethal Concentrations (Lc50) of Pathogenic Antigens and Their Applications in Vaccine Development

2020 ◽  
Author(s):  
Saganuwan Alhaji Saganuwan
Keyword(s):  
Staphylococcus Aureus ◽  
Disease Virus ◽  
Vaccine Development ◽  
Hepatitis A Virus ◽  
Lethal Dose ◽  
Vaccine Dose ◽  
Foot And Mouth Disease ◽  
Mouth Disease Virus

Abstract Objective: Lack of ideal mathematical models to qualify and quantify both pathogenicity, and virulence is a dreadful setback in development of new antimicrobials and vaccines against resistance pathogenic microorganisms. Hence, the modified arithmetical formula of Reed and Muench has been integrated with other formulas and used for determination of antigen concentration and parasites inoculums that would kill 50% of test animals (LC50).Results: Microorganisms’ antigens tested are Staphylococcus aureus, Streptococcus pneumonia, Pseudomonas aeruginosa in mice and rat, Edwardsiella ictaluri, Aeromonas hydrophila, Aeromonas veronii in fish, New Castle Disease virus in chicken, Sheep Pox Virus, Foot-and-Mouth Disease Virus and Hepatitis A virus in vitro, respectively. The LC50s for the pathogens using different routes of administrations are 1.93 x 103 (sheep poxvirus) and 1.75 x 1010 for Staphylococcus aureus (ATCC29213) in rat respectively. N is the number of vaccine dose that could neutralize the LC50.Titre index (TI) equals N log10 LC50 and provides protection against lethal dose in graded fashion which translates to protection index. Hence, parasite inoculum of 103 to 1011 could be used as basis for median lethal dose (LD50), LC50 and median bacterial concentrations (BC50) determination, pathogenic dose for immune stimulation should be sought at concentrations less than LC10.

scholarly journals Construction and Characterization of a Pseudomonas aeruginosa Mucoid Exopolysaccharide-Alginate Conjugate Vaccine

2003 ◽  
Vol 71 (7) ◽  
pp. 3875-3884 ◽  
Author(s):  
Christian Theilacker ◽  
Fadie T. Coleman ◽  
Simone Mueschenborn ◽  
Nicolas Llosa ◽  
Martha Grout ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Conjugate Vaccine ◽  
Significant Proportion ◽  
Vaccine Trial ◽  
Keyhole Limpet Hemocyanin ◽  
Opsonic Activity ◽  
Human Sera ◽  
Normal Human

ABSTRACT Deterioration of lung function in patients with cystic fibrosis (CF) is closely associated with chronic pulmonary infection with mucoid Pseudomonas aeruginosa. The mucoid exopolysaccharide (MEP) from P. aeruginosa has been shown to induce opsonic antibodies in mice that are protective against this chronic infection. MEP-specific opsonic antibodies are also commonly found in the sera of older CF patients lacking detectable P. aeruginosa infection. When used in a human vaccine trial, however, MEP only minimally induced opsonic antibodies. To evaluate whether conjugation of MEP to a carrier protein could improve its immunogenicity, we bound thiolated MEP to keyhole limpet hemocyanin (KLH) by using succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC) as a linker. In contrast to the native MEP polymer, the MEP-KLH conjugate vaccine induced high titers of MEP-specific immunoglobulin G (IgG) in C3H-HeN mice and in a rabbit. Sera from mice immunized with MEP-KLH conjugate, but not from animals immunized with comparable doses of native MEP, demonstrated opsonic killing activity. Vaccination with MEP-KLH conjugate induced opsonic antibodies broadly cross-reactive to heterologous mucoid strains of P. aeruginosa. Preexisting nonopsonic antibodies to MEP are found in normal human sera, including young CF patients, and their presence impedes the induction of opsonic antibodies. Induction of nonopsonic antibodies by either intraperitoneal injection of MEP or injection or feeding of the cross-reactive antigen, seaweed alginate, reduced the level of overall IgG elicited by follow-up immunization with the MEP-KLH conjugate. However, the opsonic activity was lower only in the sera of MEP-KLH conjugate-immunized mice with preexisting antibodies induced by MEP but not with antibodies induced by seaweed alginate. Immunization with MEP-KLH elicited a significant proportion of antibodies specific to epitopes involving O-acetate residues, and this subpopulation of antibodies mediated opsonic killing of mucoid P. aeruginosa in vitro. These results indicate that conjugation of MEP to KLH significantly enhances its immunogenicity and the elicitation of opsonic antibodies in mice and rabbits, that the conjugate induces opsonic antibodies in the presence of preexisting nonopsonic antibodies, and that opsonic antibodies to MEP are directed at epitopes that include acetate residues on the uronic acid polymer.

Optimisation of the inactivated vaccine dose against heartwater and in vitro quantification of Ehrlichia ruminantium challenge material

Vaccine ◽  
2006 ◽  
Vol 24 (22) ◽  
pp. 4747-4756 ◽  
Author(s):  
N VACHIERY ◽  
T LEFRANCOIS ◽  
I ESTEVES ◽  
S MOLIA ◽  
C SHEIKBOUDOU ◽  
...  
Keyword(s):  
Vaccine Dose ◽  
Inactivated Vaccine ◽  
Ehrlichia Ruminantium

scholarly journals Application of Median Lethal Concentration (LC50) of Pathogenic Microorganisms and Their Antigens in Vaccine Development

2020 ◽  
Author(s):  
Saganuwan Alhaji Saganuwan
Keyword(s):  
Staphylococcus Aureus ◽  
Disease Virus ◽  
Vaccine Development ◽  
Hepatitis A Virus ◽  
Lethal Dose ◽  
Vaccine Dose ◽  
Pathogenic Microorganisms ◽  
Bacterial Colony ◽  
Mouth Disease Virus

Abstract Objective: Lack of ideal mathematical models to qualify and quantify both pathogenicity, and virulence is a dreadful setback in development of new antimicrobials and vaccines against resistance pathogenic microorganisms. Hence, the modified arithmetical formula of Reed and Muench has been integrated with other formulas and used to determine bacterial colony forming unit/ viral concentration, virulence and immunogenicity. Results: Microorganisms’antigens tested are Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa in mice and rat, Edwardsiella ictaluri, Aeromonas hydrophila, Aeromonas veronii in fish, New Castle Disease virus in chicken, Sheep Pox Virus, Foot-and-Mouth Disease Virus and Hepatitis A virus in vitro, respectively. The LC50s for the pathogens using different routes of administrations are 1.93 x 103(sheep poxvirus) and 1.75 x 1010 for Staphylococcus aureus (ATCC29213) in rat respectively. Titer index (TI) equals N log10 LC50 and provides protection against lethal dose in graded fashion which translates to protection index. N is the number of vaccine dose that could neutralize the LC50. Hence, parasite inoculum of 103 to 1011may be used as basis for determination of LC50 and median bacterial concentrations (BC50).Pathogenic dose for immune stimulation should be sought at concentration about LC10.

scholarly journals Anti-SARS-CoV-2 antibody levels measured by the Advise Dx SARS-CoV-2 assay are concordant with previously available serologic assays but are not fully predictive of sterilizing immunity

2021 ◽  
Author(s):  
Benjamin T. Bradley ◽  
Andrew Bryan ◽  
Susan L. Fink ◽  
Erin A. Goecker ◽  
Pavitra Roychoudhury ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Vaccine Dose ◽  
Humoral Response ◽  
Pcr Detection ◽  
Clinical Sensitivity ◽  
Significant Difference ◽  
Antibody Assays ◽  
Unit Conversion ◽  
Antibody Levels

With the availability of widespread SARS-CoV-2 vaccination, high-throughput quantitative anti-spike serological testing will likely become increasingly important. Here, we investigated the performance characteristics of the recently FDA authorized semi-quantitative anti-spike AdviseDx SARS-CoV-2 IgG II assay compared to the FDA authorized anti-nucleocapsid Abbott Architect SARS-CoV-2 IgG, Roche elecsys Anti-SARS-CoV-2-S, EuroImmun Anti-SARS-CoV-2 ELISA, and GenScript surrogate virus neutralization assays and examined the humoral response associated with vaccination, natural protection, and breakthrough infection. The AdviseDx assay had a clinical sensitivity at 14 days post-symptom onset or 10 days post PCR detection of 95.6% (65/68, 95% CI: 87.8-98.8%) with two discrepant individuals seroconverting shortly thereafter. The AdviseDx assay demonstrated 100% positive percent agreement with the four other assays examined using the same symptom onset or PCR detection cutoffs. Using a recently available WHO International Standard for anti-SARS-CoV-2 antibody, we provide assay unit conversion factors to international units for each of the assays examined. We performed a longitudinal survey of healthy vaccinated individuals, finding median AdviseDx immunoglobulin levels peaked seven weeks post-first vaccine dose at approximately 4,000 IU/mL. Intriguingly, among the five assays examined, there was no significant difference in antigen binding level or neutralizing activity between two seropositive patients protected against SARS-CoV-2 infection in a previously described fishing vessel outbreak and five healthcare workers who experienced vaccine breakthrough of SARS-CoV-2 infection – all with variants of concern. These findings suggest that protection against SARS-CoV-2 infection cannot currently be predicted exclusively using in vitro antibody assays against wildtype SARS-CoV-2 spike. Further work is required to establish protective correlates for SARS-CoV-2 infection.

Evaluation of the immune memory response to routine HBV vaccine in Egyptian patients with Type 1 diabetes

2020 ◽  
Vol 15 (4) ◽  
pp. 215-223
Author(s):  
Helal F Hetta ◽  
Nahla M Elsherbiny ◽  
Esraa M Eloseily ◽  
Samaher F Taha ◽  
Eman Fathalla Gad ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Vaccine Dose ◽  
Immune Memory ◽  
Diabetic Patients ◽  
Peripheral Blood Mononuclear ◽  
Hbv Vaccine ◽  
Memory Response ◽  
Hbv Vaccination ◽  
Egyptian Patients

We aimed to evaluate the immune memory response to HBV vaccine in diabetic patients who had received the full HBV vaccination during infancy and to assess the need for booster doses. Blood samples were collected from children (93 diabetics and 105 controls) and university students (22 diabetics and 20 controls). Anti-HBs titer in serum and after in vitro stimulation of peripheral blood mononuclear cells with HBV vaccine was measured by ELISA. Diabetic groups had significantly lower anti-HBs levels after 10 years of the last HBV vaccine dose. The percentage of diabetic patients having protective anti-HBs titers was significantly lower than controls. In conclusion, diabetic patients had lower immune response to HBV vaccine over time, emphasizing the need for a booster dose.

scholarly journals Assessment of an LSDV-Vectored Vaccine for Heterologous Prime-Boost Immunizations against HIV

Vaccines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1281
Author(s):  
Ros Chapman ◽  
Michiel van Diepen ◽  
Nicola Douglass ◽  
Shireen Galant ◽  
Mohamed Jaffer ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Vaccine Trial ◽  
Rabbit Model ◽  
Protective Effects ◽  
Subtype C ◽  
Humoral Immune ◽  
Vector Systems ◽  
Hiv 1

The modest protective effects of the RV144 HIV-1 vaccine trial have prompted the further exploration of improved poxvirus vector systems that can yield better immune responses and protection. In this study, a recombinant lumpy skin disease virus (LSDV) expressing HIV-1 CAP256.SU gp150 (Env) and a subtype C mosaic Gag was constructed (LSDVGC5) and compared to the equivalent recombinant modified vaccinia Ankara (MVAGC5). In vitro characterization confirmed that cells infected with recombinant LSDV produced Gag virus-like particles containing Env, and that Env expressed on the surface of the cells infected with LSDV was in a native-like conformation. This candidate HIV-1 vaccine (L) was tested in a rabbit model using different heterologous vaccination regimens, in combination with DNA (D) and MVA (M) vectors expressing the equivalent HIV-1 antigens. The four different vaccination regimens (DDMMLL, DDMLML, DDLMLM, and DDLLMM) all elicited high titers of binding and Tier 1A neutralizing antibodies (NAbs), and some regimens induced Tier 1B NAbs. Furthermore, two rabbits in the DDLMLM group developed low levels of autologous Tier 2 NAbs. The humoral immune responses elicited against HIV-1 Env by the recombinant LSDVGC5 were comparable to those induced by MVAGC5.

scholarly journals Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity in uninfected and previously infected individuals

2021 ◽  
Author(s):  
Carolina Lucas ◽  
Chantal B.F. Vogels ◽  
Inci Yildirim ◽  
Jessica Rothman ◽  
Peiwen Lu ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Vaccine Dose ◽  
Neutralizing Antibody ◽  
Activation Markers ◽  
Spike Gene ◽  
Neutralization Capacity ◽  
The Impact

The emergence of SARS-CoV-2 variants with mutations in major neutralizing antibody-binding sites can affect humoral immunity induced by infection or vaccination (1-6). We analysed the development of anti-SARS-CoV-2 antibody and T cell responses in previously infected (recovered) or uninfected (naive) individuals that received mRNA vaccines to SARS-CoV-2. While previously infected individuals sustained higher antibody titers than uninfected individuals post-vaccination, the latter reached comparable levels of neutralization responses to the ancestral strain than previously infected individuals 7 days after the second vaccine dose. T cell activation markers measured upon spike or nucleocapsid peptide in vitro stimulation showed a progressive increase after vaccination in the time-points analysed. Comprehensive analysis of plasma neutralization using 16 authentic isolates of distinct locally circulating SARS-CoV-2 variants revealed a range of reduction in the neutralization capacity associated with specific mutations in the spike gene: lineages with E484K and N501Y/T (e.g., B.1.351 and P.1) had the greatest reduction, followed by lineages with L452R (e.g., B.1.617.2) or with E484K (without N501Y/T). While both groups retained neutralization capacity against all variants, plasma from previously infected vaccinated individuals displayed overall better neutralization capacity when compared to plasma from uninfected individuals that also received two vaccine doses, pointing to vaccine boosters as a relevant future strategy to alleviate the impact of emerging variants on antibody neutralizing activity.

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