scholarly journals LB11. A Single Dose of the MVA-BN Smallpox Vaccine Induces an Early Protective Antibody Response Similar to a Traditional Replicating Vaccine and Is Suitable for Emergency Scenarios

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S997-S998
Author(s):  
Jane Maclennan ◽  
Heinz Weidenthaler ◽  
Phillip Pittman ◽  
Darja Schmidt ◽  
Paul Chaplin
Keyword(s):  
Single Dose ◽  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Spontaneous Mutation ◽  
Neutralizing Antibody ◽  
Smallpox Vaccine ◽  
Group 2 ◽  
Emergency Scenarios ◽  
Group 1

Abstract Background Smallpox remains a high-priority threat due to its potential for re-emergence through events including bioterrorism and spontaneous mutation. While traditional replicating smallpox vaccines such as ACAM2000 are associated with serious side effects, the non-replicating MVA BN smallpox vaccine was developed as a safer alternative. Methods This phase 3 non-inferiority study compared indicators of efficacy between the MVA-BN smallpox vaccine and ACAM2000. The co-primary endpoints were (1) to compare vaccine-induced serum neutralizing antibodies (geometric mean titer [GMT]) at predefined Peak Visits, as measured by plaque reduction neutralization tests (PRNT) and (2) to assess the attenuation of ACAM2000-induced takes after MVA-BN administration by measuring maximum lesion area (MLA). Early neutralizing antibody GMTs at Day 14, a timepoint considered protective for traditional replicating smallpox vaccines, were also compared following single doses of either vaccine. Results A total of 440 subjects were evenly randomized to receive either 2 doses of MVA-BN followed by 1 dose of ACAM2000 at 4 week intervals (Group 1) or a single dose of ACAM2000 (Group 2). Peak neutralizing antibody GMTs were significantly higher following 2 MVA-BN doses (153.5) compared with ACAM2000 (79.3), with a ratio of 1.935 (95% CI: 1.562, 2.397). At Day 14, neutralizing antibody GMTs were equal following a single dose of either MVA BN or ACAM2000 (16.2, ratio of 0.997, 95% CI: 0.738, 1.348), with similar seroconversion rates (90.8% vs. 91.8%, respectively). The median MLA induced by ACAM2000 was significantly reduced when subjects received prior MVA-BN in Group 1 (0 mm2) compared with Group 2 (76.0 mm2), suggesting protection against orthopoxvirus. MVA BN was well tolerated, demonstrating a better safety profile than ACAM2000. Conclusion Two doses of MVA-BN induce significantly higher peak neutralizing antibody responses compared with ACAM2000. A single dose induces an early neutralizing antibody response equal to ACAM2000 at Day 14, demonstrating the suitability of MVA BN in both pre- and post-outbreak scenarios. This study was partly funded by BARDA under contract HHSO100200700034C. Disclosures Jane Maclennan, BSc MRPharmS, Bavarian Nordic (Employee), Bavarian Nordic (Employee, Shareholder), Heinz Weidenthaler, MD, Bavarian Nordic (Employee, Shareholder), Phillip Pittman, MD, Bavarian Nordic (Scientific Research Study Investigator), Darja Schmidt, PhD, Bavarian Nordic (Employee, Shareholder), Paul Chaplin, PhD, Bavarian Nordic (Board Member, Employee, Shareholder), Bavarian Nordic (Employee, Shareholder).

scholarly journals 2754. Phase 1 Trial of an mRNA-Based Combination Vaccine Against hMPV and PIV3

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S970-S970 ◽  
Author(s):  
Christine Shaw ◽  
Heather Lee ◽  
Conor Knightly ◽  
Shiva Kalidindi ◽  
Tal Zaks ◽  
...  
Keyword(s):  
Single Dose ◽  
Respiratory Tract ◽  
Neutralizing Antibodies ◽  
Phase 1 ◽  
Geometric Mean ◽  
Vaccine Dose ◽  
Neutralizing Antibody ◽  
Combination Vaccine ◽  
Tract Infections ◽  
Dose Levels

Abstract Background Human metapneumovirus (hMPV) and parainfluenza virus type 3 (PIV3) are important causes of upper and lower respiratory tract infections, particularly in young children. Despite their public health impact, no effective therapeutic or preventive options are available. mRNA-1653 is a mRNA-based investigational combination vaccine against hMPV and PIV3, and consists of two distinct mRNA sequences encoding the fusion proteins of hMPV and PIV3, co-formulated in lipid nanoparticles. Methods This phase 1, first-in-human, randomized, placebo-controlled, dose-ranging study assesses the safety and immunogenicity of mRNA-1653 in healthy adults aged 18–49. The 124-subject study evaluates four vaccine dose levels (25, 75, 150, and 300 µg) administered intramuscularly in either single-dose or two-dose (Day 1, Month 1) vaccination schedules, with follow-up through 1 year after the last vaccination. Objectives include safety and immunogenicity measured by hMPV- and PIV3-specific neutralizing antibody titers. Results An interim analysis demonstrated that the mRNA-1653 vaccine was generally well-tolerated at all dose levels. Neutralizing antibodies against hMPV and PIV3 were present at baseline in all subjects, consistent with prior exposure to both viruses. A single dose of mRNA-1653 boosted serum neutralization titers against both hMPV and PIV3, and the magnitude of boosting was similar at all dose levels. The geometric mean ratio of Month 1 to baseline titers was approximately 6 for hMPV and 3 for PIV3. A second dose of mRNA-1653 at Month 1 was not associated with further increase of hMPV or PIV3 neutralization titers. Conclusion mRNA-1653 is well-tolerated and induces a functional immune response, and is therefore a promising vaccine candidate for the prevention of pediatric respiratory tract diseases caused by hMPV and PIV3. Disclosures All authors: No reported disclosures.

scholarly journals Immunogenicity in sheep of Uruguayan commercial vaccines against bovine alphaherpesvirus 1, 5 and bovine pestiviruses

2020 ◽  
Vol 50 (4) ◽  
Author(s):  
Ingryd Merchioratto ◽  
Alana de Almeida Aurélio ◽  
Janice Machado Villela ◽  
Nicole Vieira Stone ◽  
Isac Junior Roman ◽  
...  
Keyword(s):  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Serological Response ◽  
Serum Samples ◽  
Post Vaccination ◽  
Immunological Responses ◽  
Antibody Titers ◽  
Low Levels

ABSTRACT: The serological responses induced by four commercial inactivated Uruguayan vaccines against bovine alphaherpesviruses (BoHV)-1 and -5 and bovine pestiviruses (BVDV-1, BVDV-2, and HoBiPeV) were evaluated in sheep. Thirty-seven sheep were immunized twice (day 0 and 25) and their serum samples were tested at different intervals (days 0, 25, 40, 60, and 90) post-vaccination (PV). Among the four vaccines tested, only one (G4) could induce the production of moderate neutralizing antibody titers against BoHV-1 and -5 and BVDV-1 and -2. The G3 vaccine showed a neutralizing serological response against the bovine alphaherpesviruses only. The G1 and G2 vaccines produced extremely low levels of antibodies in a few vaccinated animals only (geometric mean titers (GMT) 2.2). Similar levels of immunological responses were induced by the G4 vaccine against BoHV-1 and -5, and titers of neutralizing antibodies induced in approximately 70% of the animals are known to confer protection (GMT > 8). For bovine pestiviruses, the vaccine stimulated response of G4 against BVDV-2 was higher compared to that against BVDV-1, and extremely low for HoBiPeV. The peak of neutralizing antibodies to BoHV-1 and BVDV-1 was observed on days 40 and 60 PV, respectively. Thereafter, a remarkably decrease in neutralizing antibody response was observed at day 90 PV. These results demonstrated that tested commercial Uruguayan vaccines did not induce a serological response of adequate magnitude and duration. Thus, it is important to periodically review formulations and compositions of commercial vaccines against bovine alphaherpesviruses and pestiviruses.

scholarly journals Neutralizing Antibody Response to Pseudotype SARS-CoV-2 Differs between mRNA-1273 and BNT162b2 COVID-19 Vaccines and by History of SARS-CoV-2 Infection

2021 ◽  
Author(s):  
Harmony L. Tyner ◽  
Mark G. Thompson ◽  
Jefferey L. Burgess ◽  
Lauren Grant ◽  
Manjusha Gaglani ◽  
...  
Keyword(s):  
Antibody Response ◽  
Messenger Rna ◽  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Vaccine Dose ◽  
Neutralizing Antibody ◽  
Frontline Workers ◽  
History Of ◽  
Antibody Titers ◽  
Polymerase Chain

Background: Data on the development of neutralizing antibodies against SARS-CoV-2 after SARS-CoV-2 infection and after vaccination with messenger RNA (mRNA) COVID-19 vaccines are limited. Methods: From a prospective cohort of 3,975 adult essential and frontline workers tested weekly from August, 2020 to March, 2021 for SARS-CoV-2 infection by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) assay irrespective of symptoms, 497 participants had sera drawn after infection (170), vaccination (327), and after both infection and vaccination (50 from the infection population). Serum was collected after infection and each vaccine dose. Serum-neutralizing antibody titers against USA-WA1/2020-spike pseudotype virus were determined by the 50% inhibitory dilution. Geometric mean titers (GMTs) and corresponding fold increases were calculated using t-tests and linear mixed effects models. Results: Among 170 unvaccinated participants with SARS-CoV-2 infection, 158 (93%) developed neutralizing antibodies (nAb) with a GMT of 1,003 (95% CI=766-1,315). Among 139 previously uninfected participants, 138 (99%) developed nAb after mRNA vaccine dose-2 with a GMT of 3,257 (95% CI = 2,596-4,052). GMT was higher among those receiving mRNA-1273 vaccine (GMT =4,698, 95%CI= 3,186-6,926) compared to BNT162b2 vaccine (GMT=2,309, 95%CI=1,825-2,919). Among 32 participants with prior SARS-CoV-2 infection, GMT was 21,655 (95%CI=14,766-31,756) after mRNA vaccine dose-1, without further increase after dose-2. Conclusions: A single dose of mRNA vaccine after SARS-CoV-2 infection resulted in the highest observed nAb response. Two doses of mRNA vaccine in previously uninfected participants resulted in higher nAb to SARS-CoV-2 than after one dose of vaccine or SARS-CoV-2 infection alone. Neutralizing antibody response also differed by mRNA vaccine product.

scholarly journals Persistence of Rabies Antibody 5 Years after Postexposure Prophylaxis with Vero Cell Antirabies Vaccine and Antibody Response to a Single Booster Dose

2011 ◽  
Vol 18 (9) ◽  
pp. 1477-1479 ◽  
Author(s):  
Xiaowei Zhang ◽  
Zhenggang Zhu ◽  
Chuanlin Wang
Keyword(s):  
Antibody Response ◽  
Vero Cell ◽  
Neutralizing Antibodies ◽  
Booster Dose ◽  
Seroconversion Rate ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Safe Side ◽  
Patient Will ◽  
High Degree

ABSTRACTThis study was done to investigate the antibody response to a Vero cell antirabies vaccine, the persistence of antibody for 5 years, and the effect of a booster dose after this interval. From August 2005 to February 2011, a total of 195 patients were enrolled into our study due to an animal bite. The Essen intramuscular (i.m.) regimen, which is recommended by the WHO for modern vaccines used in postexposure treatment, was adopted in this study. Blood samples were obtained on day 0, day 7, day 14, day 45, year 1, year 2, year 3, year 4, year 5, and year 5 plus 14 days. Immunogenicity was evaluated by the titration of neutralizing antibodies with a rapid fluorescent focus inhibition test (RFFIT). Seroconversion was expressed as the seroconversion rate (SCR). A secondary quantitative evaluation criterion, other than the seroconversion level, was the geometric mean titer (GMT). Of the 195 enrolled patients, 168 (86.4%) of them completed the whole study. No serious adverse reactions to the vaccine were reported during vaccination, the 5-year follow-up period, or revaccination. On day 14, the rabies antibody GMT value was 8.87 IU/ml in the vaccinees. During the next 5 years, the SCR in the ChengDa vaccine group gradually decreased to 34.0% at year 5, down from 90.5% at year 1. There was a significant booster effect: the GMT was 15.22 IU/ml on year 5 plus 14 days. Our findings demonstrate that the ChengDa rabies vaccine offers an alternative with a high degree of efficacy and yet limited side effects and ensures that the exposed patient will be on the safe side of the risk of rabies by the 14th day. Moreover, when followed by a booster dose 5 years later, it could boost the immunity. A further booster is effective in inducing a good neutralizing antibody response even after an interval of 5 years.

scholarly journals In vitro neutralizing activity of BNT162b2 mRNA-induced antibodies against full B.1.351 SARS-CoV-2 variant

2021 ◽  
Author(s):  
Federico García ◽  
Esther Serrano-Conde ◽  
Alba Leyva ◽  
Ana Fuentes-Lopez ◽  
Adolfo de Salazar ◽  
...  
Keyword(s):  
Single Dose ◽  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Healthcare Workers ◽  
Neutralizing Antibody ◽  
Neutralization Activity ◽  
Neutralizing Activity ◽  
Study Participants ◽  
Prior Infection

Background: SARS-CoV-2 variation represents a serious challenge to current COVID-19 vaccines. Recent reports suggest that B.1.351 and other variants may escape the neutralization activity of the antibodies generated by current vaccines. Methods: Ninety-nine healthcare workers undertaking BNT162b2 mRNA vaccination were sampled at baseline, on the day of the second dose, and 14 days after the latter. Neutralization activity against SARS-CoV-2 B.1, B.1.1.7 and B.1.351 was investigated using a Vero-E6 model. Results: Eleven of the study participants had prior infection with SARS-CoV-2. Neutralization titers against the B.1 and the B.1.1.7 variants were not statistically different and were significantly higher than titers against the B.1.351 variant across pre-exposed and non-pre-exposed vaccinated individuals ( p<0.01). While all vaccinated individuals presented neutralizing antibodies against B.1 and B 1.1.7 after the second dose, 14% were negative against B.1.351, and 76% had low titers (1/20-1/80). Pre-exposed vaccinated individuals showed higher titers than non-pre-exposed after the first (median titers of 1/387 versus 1/28, respectively) and the second doses (1/995 versus 1/703, respectively). As high as 72% of the pre-exposed vaccinees presented titers >1/80 after a single dose, while only 11% of non-exposed vaccinated individuals had titers >1/80. Conclusions: BNT162b2 mRNA-induced antibodies show a lower in vitro neutralizing activity against B.1.351 variant compared to neutralization against B.1.1.7 or B.1 variants. Interestingly, for individuals pre-exposed to SARS-CoV-2, one dose of BNT162b2 mRNA may be adequate to produce neutralizing antibodies against B.1.1.7 and B.1, while two doses of BNT162b2 mRNA provide optimal neutralizing antibody response against B.1.351 too.

Administration of Single-Dose Antibiotic Does Not Decrease Oronasal Fistula Rates After Primary Palatoplasty

2021 ◽  
pp. 105566562199265
Author(s):  
Ishwarya Shradha Mamidi ◽  
Esperanza Mantilla-Rivas ◽  
Brynne A. Ichiuji ◽  
Md Sohel Rana ◽  
Karen I. Ramirez ◽  
...  
Keyword(s):  
Single Dose ◽  
Fistula Formation ◽  
Readmission Rates ◽  
Oronasal Fistula ◽  
Inadequate Sample Size ◽  
Perioperative Antibiotics ◽  
The Difference ◽  
Group 2 ◽  
National Databases ◽  
Group 1

Objective: Oronasal fistula (ONF) is a known complication after primary palatoplasty (PP). Studies investigating the effect of perioperative antibiotics on fistula rates after PP are limited by inadequate sample size or reliance on self-reporting through national databases. In this study, the authors evaluated the association between single-dose perioperative antibiotics and postoperative fistula rates after PP at a single institution. Design: A retrospective study. Participants: Children younger than 2 years who underwent PP from April 2009 to September 2019 were included. Interventions: Patients were divided into 2 categories: Group 1 received a single intraoperative dose of IV antibiotic, while group 2 did not. Main Outcome Measure(s): Outcome measures included ONF formation, length of stay (LOS), and 30-day readmission rates. Multivariable firth logistic regression, quantile regression, and χ2 tests were performed. Results: Of the 424 patients, 215 and 209 patients were in groups 1 and 2, respectively. The overall ONF rate was 1.9% among all patients. Patients in group 1 experienced an ONF rate of 3.3%, while patients in group 2 had an ONF rate of 0.5%. After correcting for confounding variables, the difference in ONF rates was not statistically different ( P = .68). Median LOS was 35.7 hours and 35.5 hours ( P = .17), while the rate of readmission within 30 days was 4.7% and 2.4% for group 1 and 2, respectively ( P = .96). Conclusions: Administration of a single-dose perioperative antibiotic did not decrease fistula formation after PP, nor did it affect the patient’s LOS or 30-day readmission rate.

scholarly journals SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nanda Kishore Routhu ◽  
Narayanaiah Cheedarla ◽  
Venkata Satish Bollimpelli ◽  
Sailaja Gangadhara ◽  
Venkata Viswanadh Edara ◽  
...  
Keyword(s):  
Antibody Response ◽  
Antibody Titer ◽  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Neutralizing Antibody ◽  
Significant Loss ◽  
Lung Pathology ◽  
Live Virus ◽  
Suitable Candidate ◽  
Immune Pathology

AbstractThere is a great need for the development of vaccines that induce potent and long-lasting protective immunity against SARS-CoV-2. Multimeric display of the antigen combined with potent adjuvant can enhance the potency and longevity of the antibody response. The receptor binding domain (RBD) of the spike protein is a primary target of neutralizing antibodies. Here, we developed a trimeric form of the RBD and show that it induces a potent neutralizing antibody response against live virus with diverse effector functions and provides protection against SARS-CoV-2 challenge in mice and rhesus macaques. The trimeric form induces higher neutralizing antibody titer compared to monomer with as low as 1μg antigen dose. In mice, adjuvanting the protein with a TLR7/8 agonist formulation alum-3M-052 induces 100-fold higher neutralizing antibody titer and superior protection from infection compared to alum. SARS-CoV-2 infection causes significant loss of innate cells and pathology in the lung, and vaccination protects from changes in innate cells and lung pathology. These results demonstrate RBD trimer protein as a suitable candidate for vaccine against SARS-CoV-2.

A Neutralizing Antibody Selected from Plasma Cells That Binds to Group 1 and Group 2 Influenza A Hemagglutinins

Science ◽  
2011 ◽  
Vol 333 (6044) ◽  
pp. 850-856 ◽  
Author(s):  
D. Corti ◽  
J. Voss ◽  
S. J. Gamblin ◽  
G. Codoni ◽  
A. Macagno ◽  
...  
Keyword(s):  
Influenza A ◽  
Plasma Cells ◽  
Neutralizing Antibody ◽  
Group 2 ◽  
Group 1
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