scholarly journals Strong immunogenicity of heterologous prime-boost immunizations with the experimental vaccine GRAd-COV2 and BNT162b2 or ChAdOx1-nCOV19

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Chiara Agrati ◽  
Stefania Capone ◽  
Concetta Castilletti ◽  
Eleonora Cimini ◽  
Giulia Matusali ◽  
...  
Keyword(s):  
Immune Response ◽  
Single Dose ◽  
Neutralizing Antibodies ◽  
Small Sample Size ◽  
Phase 1 ◽  
Vaccination Campaign ◽  
Small Sample ◽  
Vaccine Platform ◽  
Ideal Tool ◽  
Cellular Immune

AbstractHere we report on the humoral and cellular immune response in eight volunteers who autonomously chose to adhere to the Italian national COVID-19 vaccination campaign more than 3 months after receiving a single-administration GRAd-COV2 vaccine candidate in the context of the phase-1 clinical trial. We observed a clear boost of both binding/neutralizing antibodies as well as T-cell responses upon receipt of the heterologous BNT162b2 or ChAdOx1-nCOV19 vaccines. These results, despite the limitation of the small sample size, support the concept that a single dose of an adenoviral vaccine may represent an ideal tool to effectively prime a balanced immune response, which can be boosted to high levels by a single dose of a different vaccine platform.

scholarly journals Strong immunogenicity of heterologous prime-boost immunizations with the experimental vaccine GRAd-COV2 and BNT162b2 or ChAdOx1-nCOV19

2021 ◽  
Author(s):  
Chiara Agrati ◽  
Stefania Capone ◽  
Concetta Castilletti ◽  
Eleonora Cimini ◽  
Giulia Matusali ◽  
...  
Keyword(s):  
Immune Response ◽  
Single Dose ◽  
Neutralizing Antibodies ◽  
Small Sample Size ◽  
Phase 1 ◽  
Vaccination Campaign ◽  
Small Sample ◽  
Vaccine Platform ◽  
Ideal Tool ◽  
Cellular Immune

Here we report on the humoral and cellular immune response in eight volunteers who autonomously chose to adhere to the Italian national COVID-19 vaccination campaign more than 3 months after receiving a single administration GRAd-COV2 vaccine candidate in the context of the phase 1 clinical trial. We observed a clear boost of both binding/neutralizing antibodies as well as T cell responses upon receipt of the heterologous BNT162b2 or ChAdOx1-nCOV19 vaccines. These results, despite the limitation of the small sample size, support the concept that a single-dose of an adenoviral vaccine may represent an ideal tool to effectively prime a balanced immune response, which can be boosted to high levels by a single dose of a different vaccine platform.

scholarly journals Safety and Immunogenicity of Heterologous and Homologous 2-Dose Regimens of Adenovirus Serotype 26– and Modified Vaccinia Ankara–Vectored Ebola Vaccines: A Randomized, Controlled Phase 1 Study

2020 ◽  
Author(s):  
Neil Goldstein ◽  
Viki Bockstal ◽  
Stephan Bart ◽  
Kerstin Luhn ◽  
Cynthia Robinson ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Ebola Virus ◽  
Phase 1 ◽  
Booster Vaccination ◽  
Controlled Study ◽  
Adenovirus Serotype ◽  
Cellular Immune Responses ◽  
High Doses ◽  
Cellular Immune

Abstract Background This phase 1 placebo-controlled study assessed the safety and immunogenicity of 2-dose regimens of Ad26.ZEBOV (adenovirus serotype 26 [Ad26]) and MVA-BN-Filo (modified vaccinia Ankara [MVA]) vaccines with booster vaccination at day 360. Methods Healthy US adults (N = 164) randomized into 10 groups received saline placebo or standard or high doses of Ad26 or MVA in 2-dose regimens at 7-, 14-, 28-, or 56-day intervals; 8 groups received booster Ad26 or MVA vaccinations on day 360. Participants reported solicited and unsolicited reactogenicity; we measured immunoglobulin G binding, neutralizing antibodies and cellular immune responses to Ebola virus glycoprotein. Results All regimens were well tolerated with no serious vaccine-related adverse events. Heterologous (Ad26,MVA [dose 1, dose 2] or MVA,Ad26) and homologous (Ad26,Ad26) regimens induced humoral and cellular immune responses 21 days after dose 2; responses were higher after heterologous regimens. Booster vaccination elicited anamnestic responses in all participants. Conclusions Both heterologous and homologous Ad26,MVA Ebola vaccine regimens are well tolerated in healthy adults, regardless of interval or dose level. Heterologous 2-dose Ad26,MVA regimens containing an Ebola virus insert induce strong, durable humoral and cellular immune responses. Immunological memory was rapidly recalled by booster vaccination, suggesting that Ad26 booster doses could be considered for individuals at risk of Ebola infection, who previously received the 2-dose regimen.

scholarly journals Comparative kinetics of SARS-CoV-2 anti-spike protein RBD IgGs and neutralizing antibodies in convalescent and naïve recipients of the BNT162b2 mRNA vaccine versus COVID-19 patients

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ioannis P. Trougakos ◽  
Evangelos Terpos ◽  
Christina Zirou ◽  
Aimilia D. Sklirou ◽  
Filia Apostolakou ◽  
...  
Keyword(s):  
Immune Response ◽  
Neutralizing Antibodies ◽  
Mononuclear Cells ◽  
Natural Infection ◽  
Severe Disease ◽  
Vaccination Campaign ◽  
Hospitalized Patients ◽  
Peripheral Blood Mononuclear ◽  
Post Vaccination ◽  
Antibody Titers

Abstract Background Coronavirus SARS-CoV-2, the causative agent of COVID-19, has caused a still evolving global pandemic. Given the worldwide vaccination campaign, the understanding of the vaccine-induced versus COVID-19-induced immunity will contribute to adjusting vaccine dosing strategies and speeding-up vaccination efforts. Methods Anti-spike-RBD IgGs and neutralizing antibodies (NAbs) titers were measured in BNT162b2 mRNA vaccinated participants (n = 250); we also investigated humoral and cellular immune responses in vaccinated individuals (n = 21) of this cohort 5 months post-vaccination and assayed NAbs levels in COVID-19 hospitalized patients (n = 60) with moderate or severe disease, as well as in COVID-19 recovered patients (n = 34). Results We found that one (boosting) dose of the BNT162b2 vaccine triggers robust immune (i.e., anti-spike-RBD IgGs and NAbs) responses in COVID-19 convalescent healthy recipients, while naïve recipients require both priming and boosting shots to acquire high antibody titers. Severe COVID-19 triggers an earlier and more intense (versus moderate disease) immune response in hospitalized patients; in all cases, however, antibody titers remain at high levels in COVID-19 recovered patients. Although virus infection promotes an earlier and more intense, versus priming vaccination, immune response, boosting vaccination induces antibody titers significantly higher and likely more durable versus COVID-19. In support, high anti-spike-RBD IgGs/NAbs titers along with spike (vaccine encoded antigen) specific T cell clones were found in the serum and peripheral blood mononuclear cells, respectively, of vaccinated individuals 5 months post-vaccination. Conclusions These findings support vaccination efficacy, also suggesting that vaccination likely offers more protection than natural infection. Graphical abstract

scholarly journals Heterologous vaccination regimens with self-amplifying RNA and Adenoviral COVID vaccines induce superior immune responses than single dose vaccine regimens in mice

2021 ◽  
Author(s):  
Alexandra J Spencer ◽  
Paul F McKay ◽  
Sandra Belij-Rammerstorfer ◽  
Marta Ulaszewska ◽  
Cameron D Bissett ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Single Dose ◽  
Cytotoxic T Cells ◽  
High Titre ◽  
Limited Data ◽  
Neutralising Antibodies ◽  
Vectored Vaccine ◽  
Cellular Immune ◽  
Dose Vaccine

AbstractSeveral vaccines have demonstrated efficacy against SARS-CoV-2 mediated disease, yet there is limited data on the immune response induced by heterologous vaccination regimens using alternate vaccine modalities. Here, we present a detailed description of the immune response, in mice, following vaccination with a self-amplifying RNA (saRNA) vaccine and an adenoviral vectored vaccine (ChAdOx1 nCoV-19/AZD1222) against SARS-CoV-2. We demonstrate that antibody responses are higher in two dose heterologous vaccination regimens than single dose regimens, with high titre neutralising antibodies induced. Importantly, the cellular immune response after a heterologous regimen is dominated by cytotoxic T cells and Th1+ CD4 T cells which is superior to the response induced in homologous vaccination regimens in mice.

scholarly journals Decreased Immune Response in Alexithymic Women: A One-Year Longitudinal Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Olivier Guilbaud ◽  
Claire Perrin ◽  
Florence Curt ◽  
Gérard Chaouat ◽  
Corinne Dugré-Le Bigre ◽  
...  
Keyword(s):  
Immune Response ◽  
Longitudinal Study ◽  
Small Sample Size ◽  
Peripheral Blood Lymphocytes ◽  
Small Sample ◽  
Major Type ◽  
Cross Sectional ◽  
Healthy Women ◽  
One Year

Although previous cross-sectional studies suggested significantly dysregulated immune response in alexithymia, there is a lack of longitudinal studies. We sought to determine the reliability of the reported relationship between alexithymia and decreased immune response in a longitudinal study. Thirty-eight healthy women who had participated in a cross-sectional study were recontacted 1-year later. Of this sample, 26 were finally included: 13 females who had been found to be alexithymic, and 13 females who were classified as non-alexithymic under the 20-item Toronto Alexithymia Scale during the first phase of the study. A year later, they were still healthy women without any psychiatric disorders, their ages now ranging from 19 to 28 years old. Lymphocyte subset counts (CD4, CD8), in vitro production of interleukin 1β (IL-1β), IL-2, IL-4, and IL-10 by phytohemagglutinin stimulated peripheral blood lymphocytes, as well as serum cortisol levels, were compared between women with and without alexithymia. One-year later, alexithymic women still had significantly lowered in vitro production of IL-2 and IL-4, with lowered IL-2/IL-10 ratio and a reduced percentage of CD4. This is the first ever published study assessing cytokine production during a follow-up of alexithymics. Although our results should be interpreted with caution due the small sample size, they suggest a sustained reduction in both major type 1 and type 2 cytokines while the former seems to be more affected. The potential long-term health impact, if any, is still to be determined.

scholarly journals Development of a Multi-Antigenic SARS-CoV-2 Vaccine Using a Synthetic Poxvirus Platform

2020 ◽  
Author(s):  
Flavia Chiuppesi ◽  
Marcela d’Alincourt Salazar ◽  
Heidi Contreras ◽  
Vu Nguyen ◽  
Joy Martinez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Vaccine Candidate ◽  
Vaccine Platform ◽  
Synthetic Dna ◽  
Cellular Immune Responses ◽  
Global Pandemic ◽  
Immunodominant Antigens ◽  
Cellular Immune

Abstract Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we used this novel vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a novel vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.

scholarly journals Immune Response to an Acute Moderate Dose of Alcohol in Healthy Young Adults

2020 ◽  
Vol 55 (6) ◽  
pp. 616-623
Author(s):  
Mollie A Monnig ◽  
Philip S Lamb ◽  
Jose M Parra ◽  
Patricia A Cioe ◽  
Christina M Martone ◽  
...  
Keyword(s):  
Immune Response ◽  
Small Sample Size ◽  
Heavy Drinking ◽  
Alcohol Concentration ◽  
Small Sample ◽  
Self Report ◽  
Placebo Condition ◽  
Alcohol Craving ◽  
Linear Decrease ◽  
Cluster Of Differentiation

Abstract Prior research on alcohol and the immune system has tended to focus on binge doses or chronic heavy drinking. The aim of this single-session preliminary study was to characterize immune response to moderate alcohol (0.60 g alcohol per kilogram body weight) in healthy, nonchronic drinkers. The sample (N = 11) averaged 26.6 years of age and was balanced in gender. Plasma samples were collected at baseline and 1, 2 and 3 hours postconsumption. Markers of microbial translocation [lipopolysaccharide (LPS)] and innate immune response [LPS-binding protein (LBP), soluble cluster of differentiation 14 (sCD14), and selected cytokines] were measured using immunoassays. Participants completed self-report questionnaires on subjective alcohol response and craving. Linear mixed models were used to assess changes in biomarkers and self-report measures. Breath alcohol concentration peaked at 0.069 ± 0.008% 1 hour postconsumption. LPS showed a significant linear decrease. LBP and sCD14 showed significant, nonlinear (U-shaped) trajectories wherein levels decreased at 1 hour then rebounded by 3 hours. Of nine cytokines tested, only MCP-1 and IL-8 were detectable in ≥50% of samples. IL-8 did not change significantly. MCP-1 showed a significant linear decrease and also accounted for significant variance in alcohol craving, with higher levels associated with stronger craving. Results offer novel evidence on acute immune response to moderate alcohol. Changes in LBP and sCD14, relative to LPS, may reflect their role in LPS clearance. Results also support further investigation into the role of MCP-1 in alcohol craving. Limitations include small sample size and lack of a placebo condition.

Modeling of pharmacodynamic (PD) biomarkers (BM) related to CDK4/6 inhibition and exploratory BM-response (progression free survival [PFS]) analyses in patients with advanced breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14528-e14528
Author(s):  
Yanke Yu ◽  
Yuan Liu ◽  
Diane Dan Wang
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Time Course ◽  
Small Sample Size ◽  
Phase 1 ◽  
Small Sample ◽  
Advanced Breast ◽  
Longitudinal Change ◽  
Indirect Response Model ◽  
The Relationship

e14528 Background: Palbociclib (PAL) is an oral inhibitor of cyclin-dependent kinase 4 and 6 (CDK4/6) approved for advanced breast cancer (ABC). In a clinical trial, the expression levels of PD BMs related to PAL effect, including thymidine kinase (TK) in serum and phosphor-Rb (pRb) and Ki67 in skin tissues, were measured at both baseline and post-treatment in patients with ABC treated with PAL plus letrozole (LET). Pharmacokinetic (PK)/PD modeling was conducted previously to characterize the longitudinal change of pRb and Ki67. The PK/PD was further evaluated for TK and exploratory analyses were conducted to evaluate the relationship between PFS and all three BMs. Methods: The present analyses used data from a Phase 1 study evaluating the PK, PD, safety and efficacy of PAL plus LET in 26 Chinese women with ABC. A 2 compartment model was used to describe the PK of PAL. A precursor-dependent indirect response model was developed to describe the TK time course after PAL treatment. PAL effect was modeled as Imax inhibitory model. Cox proportional hazard model was used to assess the correlation of PFS with three BM metrics (baseline BM, simulated lowest BM and maximum BM change in Cycle 1). Results: The BM data included 194 TK observations from 26 patients. The PK/PD models adequately described the longitudinal change of TK, and showed PAL caused TK reduction. The estimated IC50 value was 49.5 ng/mL, similar to those for pRb and Ki67. The BM-response analyses for PFS showed that correlation was found for TK. There was a significant correlation between PFS and baseline TK (BTK) and minimum TK (MTK) in Cycle 1. A longer PFS was associated with lower BTK and lower MTK. A trend for longer PFS with higher maximum TK change in Cycle 1 was observed although the relationship was not statistically significant. Conclusions: PAL exposure had significant correlation with the reduction of all three BMs. Longer PFS was associated with lower BTK and MTK. Due to the small sample size (N = 26), this analyses result need to be confirmed in a larger study.

scholarly journals Successful Boosting of a DNA Measles Immunization with an Oral Plant-Derived Measles Virus Vaccine

2002 ◽  
Vol 76 (15) ◽  
pp. 7910-7912 ◽  
Author(s):  
Diane E. Webster ◽  
Michelle L. Cooney ◽  
Zhongjun Huang ◽  
Damien R. Drew ◽  
Ian A. Ramshaw ◽  
...  
Keyword(s):  
Immune Response ◽  
Single Dose ◽  
Global Health ◽  
Virus Vaccine ◽  
Neutralizing Antibodies ◽  
Measles Virus ◽  
Vaccination Strategy ◽  
Health Concern ◽  
Dna Immunization ◽  
Edible Plant

ABSTRACT Despite eradication attempts, measles remains a global health concern. Here we report results that demonstrate that a single-dose DNA immunization followed by multiple boosters, delivered orally as a plant-derived vaccine, can induce significantly greater quantities of measles virus-neutralizing antibodies than immunization with either DNA or plant-derived vaccines alone. This represents the first demonstration of an enhanced immune response to a prime-boost vaccination strategy combining a DNA vaccine with edible plant technology.

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