scholarly journals SARS-CoV-2 Omicron Neutralization After Heterologous Vaccine Boosting

2022 ◽  
Author(s):  
Kirsten E Lyke ◽  
Robert L Atmar ◽  
Clara P. Dominguez Islas ◽  
Christine M. Posavad ◽  
Daniel Szydlo ◽  
...  
Keyword(s):  
Single Dose ◽  
Humoral Immunity ◽  
Booster Dose ◽  
Geometric Mean ◽  
Age Groups ◽  
Neutralizing Antibody ◽  
Ongoing Study ◽  
Subset Analysis ◽  
Heterologous Boost

As part of an ongoing study assessing homologous and heterologous booster vaccines, following primary EUA series, we assessed neutralization of D614G and Omicron variants prior to and 28 days after boost. Subset analysis was done in six combinations (N = 10/group): four homologous primary-booster combinations included mRNA-1273 two-dose priming followed by boosting with 100-μg or 50-μg mRNA-1273, Ad26.COV2.S single-dose priming followed by Ad26.COV2.S booster and BNT162b2 two-dose priming followed by BNT162b2 boosting; and two heterologous primary-booster combinations: BNT162b2 followed by Ad26.COV2.S and Ad26.COV2.S followed by BNT162b2. Neutralizing antibody (Nab) titers to D614G on the day of boost (baseline) were detected in 85-100% of participants, with geometric mean titers (GMT) of 71-343 in participants who received an mRNA vaccine series versus GMTs of 35-41 in participants primed with Ad26.OV2.S. Baseline NAb titers to Omicron were detected in 50-90% of participants who received an mRNA vaccine series (GMT range 12.8-24.5) versus 20-25% among participants primed with Ad26.COV2.S. The booster dose increased the neutralizing GMT in most combinations to above 1000 for D614G and above 250 for Omicron by Day 29. Homologous prime-boost Ad26.COV2.S had the lowest NAb on Day 29 (D614G GMT 128 and Omicron GMT 45). Results were similar between age groups. Most homologous and heterologous boost combinations examined will increase humoral immunity to the Omicron variant.

scholarly journals Durability of antibody responses elicited by a single dose of Ad26.COV2.S and substantial increase following late boosting

2021 ◽  
Author(s):  
Jerald Sadoff ◽  
Mathieu Le Gars ◽  
Vicky Cardenas ◽  
Georgi Shukarev ◽  
Nathalie Vaissiere ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Single Dose ◽  
Booster Dose ◽  
Age Groups ◽  
Neutralizing Antibody ◽  
Primary Vaccination ◽  
Antibody Responses ◽  
Binding Antibody ◽  
Antibody Levels ◽  
The Impact

AbstractBackgroundWe evaluated the durability of SARS-CoV-2 antibody levels elicited by the single dose Janssen COVID-19 vaccine, Ad26.COV2.S, and the impact on antibody responses of boosting with Ad26.COV2.S after 6 months in clinical trial participants.MethodsSpike-binding antibody and SARS-CoV-2 neutralizing antibody levels elicited by a single-dose Ad26.COV2.S (5×1010 viral particles [vp]) primary regimen and booster doses (5×1010 vp and 1.25×1010 vp) were assessed by ELISA and wild-type VNA in sera from participants in a Phase 1/2a clinical trial (Cohort 1a, 18–55 years old, N=25; Cohort 2a, 18–55 years old boosted at 6 months, N=17; Cohort 3, ≥65 years old, N=22) and a Phase 2 clinical trial (18–55 and ≥65-year old participants boosted at 6 months, total N=73). Neutralizing antibody levels were determined approximately 8 months after the primary vaccination in participants aged 18–55 years and approximately 9 months in participants aged ≥65 years. Binding antibody levels were evaluated 6 months after primary vaccination and 7- and 28-days after booster doses in both age groups.ResultsA single dose of Ad26.COV2.S elicited neutralizing antibodies that remained largely stable for approximately 8–9 months and binding antibodies that remained stable for at least 6 months irrespective of age group. A 5×1010 vp booster dose at 6 months post prime vaccination in 18–55-year-old adults elicited a steep and robust 9-fold increase at Day 7 post boost compared to Day 29 levels following the initial immunization. A lower booster dose of 1.25×1010 vp at 6 months in adults 18–55 and ≥65 years of age also elicited a rapid and high increase of 6–7.7 fold at Day 28 post boost compared to Day 29 levels following the initial immunization, with similar magnitude of post-boost responses in both age groups.ConclusionsA single dose of Ad26.COV2.S, which demonstrated protection in a Phase 3 efficacy trial, elicited durable neutralizing and binding antibodies for at least 8 and 6 months, respectively, in adults >18 years of age at levels similar to Day 29 responses. A 5×1010 vp or 1.25×1010 vp booster dose at 6 months elicited rapid and robust increases in spike binding antibody levels. The anamnestic responses after booster immunization imply robust immune memory elicited by single-dose Ad26.COV2.S.

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 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 Evaluation of a SARS-CoV-2 Vaccine NVX-CoV2373 in Younger and Older Adults

2021 ◽  
Author(s):  
Neil Formica ◽  
Raburn Mallory ◽  
Gary Albert ◽  
Michelle Robinson ◽  
Joyce Plested ◽  
...  
Keyword(s):  
Dose Regimen ◽  
Phase 1 ◽  
Geometric Mean ◽  
Age Groups ◽  
Safety Data ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type

Background NVX CoV2373 is a recombinant severe acute respiratory coronavirus 2 (rSARS-CoV-2) nanoparticle vaccine composed of trimeric full-length SARS CoV-2 spike glycoproteins and Matrix-M1 adjuvant. Methods The phase 2 component of our randomized, placebo-controlled, phase 1-2 trial was designed to identify which dosing regimen of NVX-CoV2373 should move forward into late phase studies in younger (18-59 years) and older (60-84 years) participants and was based on immunogenicity and safety data through day 35 (14 days after the second dose). Participants were randomly assigned to receive either one or two intramuscular doses of 5-microgram or 25-microgram NVX-CoV2373 or placebo, 21 days apart. Primary endpoints were immunoglobulin G (IgG) anti-spike protein response, 7 day solicited reactogenicity, and unsolicited adverse events. A key secondary endpoint was wild type virus neutralizing antibody response. Results After randomization, approximately 250 participants each were assigned to one of four vaccine groups or placebo. Of these, approximately 45% were older participants. Reactogenicity was predominantly mild to moderate in severity and of short duration (median <3 days) after first and second vaccination with NVX-CoV2373, with higher frequencies and intensity after second vaccination and with the higher dose, and occurred less frequently and was of lower intensity in older participants. The two-dose regimen of 5-microgram NVX-CoV2373 induced robust geometric mean titer (GMT) IgG anti-spike protein (65,019 and 28,137 EU/mL) and wild-type virus neutralizing antibody (2201 and 981 titers) responses in younger and older participants, respectively, with seroconversion rates of 100% in both age groups. Neutralizing antibody responses exceeded those seen in convalescent sera for both age groups. Conclusions The study confirmed that the two-dose regimen of 5 microgram NVX CoV2373 is highly immunogenic and well tolerated in both younger and older participants. (Funded by the Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number: NCT04368988).

scholarly journals Effectiveness of the SA 14-14-2 Live-Attenuated Japanese Encephalitis Vaccine in Myanmar

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 568
Author(s):  
Mya Myat Ngwe Tun ◽  
Aung Kyaw Kyaw ◽  
Khine Mya Nwe ◽  
Shingo Inoue ◽  
Kyaw Zin Thant ◽  
...  
Keyword(s):  
Japanese Encephalitis ◽  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Vaccination Campaign ◽  
Age Groups ◽  
Neutralizing Antibody ◽  
Blood Collection ◽  
Cross Sectional ◽  
Single Time ◽  
Japanese Encephalitis Vaccine

Myanmar is an endemic country for the Japanese encephalitis virus (JEV), and the SA-14-14-2 live-attenuated JEV vaccine was first introduced as a catch-up vaccination campaign in 2017. To determine the effectiveness of vaccination by means of neutralizing antibody titers against JEV, a cross-sectional descriptive study was conducted among five to 15-year-old monastic school children in Mandalay, Myanmar. A total of 198 students who had received vaccines were recruited, and single-time investigation of anti-JEV IgG and neutralizing antibodies against wild-type JEV were determined using anti-JEV IgG ELISA and plaque reduction neutralization tests (PRNT50). All students 100% (198/198) showed positive results on the anti-JEV IgG ELISA, and 87% (172/198) of the students had neutralizing antibodies against JEV six months after immunization. The geometric mean titers of both IgG antibodies and neutralizing antibodies increased with the participants’ age groups, and statistically significant differences in anti-JEV IgG titers were noted across age groups. In this study, we could not investigate the persistence of neutralizing antibodies as only single-time blood collection was done. This study, which is the first report of JEV vaccination among children in Myanmar, showed similar neutralizing antibody production rates among vaccinated individuals as did studies in other countries.

scholarly journals Decreased humoral immunity to mumps in young adults immunized with MMR vaccine in childhood

2019 ◽  
Vol 116 (38) ◽  
pp. 19071-19076 ◽  
Author(s):  
Mohammed Ata Ur Rasheed ◽  
Carole J. Hickman ◽  
Marcia McGrew ◽  
Sun Bae Sowers ◽  
Sara Mercader ◽  
...  
Keyword(s):  
Young Adults ◽  
Humoral Immunity ◽  
Close Contact ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
The United States ◽  
Enzyme Linked Immunosorbent Assay ◽  
Wild Type ◽  
Contributing Factors ◽  
Mmr Vaccine

In the past decade, multiple mumps outbreaks have occurred in the United States, primarily in close-contact, high-density settings such as colleges, with a high attack rate among young adults, many of whom had the recommended 2 doses of mumps-measles-rubella (MMR) vaccine. Waning humoral immunity and the circulation of divergent wild-type mumps strains have been proposed as contributing factors to mumps resurgence. Blood samples from 71 healthy 18- to 23-year-old college students living in a non-outbreak area were assayed for antibodies and memory B cells (MBCs) to mumps, measles, and rubella. Seroprevalence rates of mumps, measles, and rubella determined by IgG enzyme-linked immunosorbent assay (ELISA) were 93, 93, and 100%, respectively. The index standard ratio indicated that the concentration of IgG was significantly lower for mumps than rubella. High IgG avidity to mumps Enders strain was detected in sera of 59/71 participants who had sufficient IgG levels. The frequency of circulating mumps-specific MBCs was 5 to 10 times lower than measles and rubella, and 10% of the participants had no detectable MBCs to mumps. Geometric mean neutralizing antibody titers (GMTs) by plaque reduction neutralization to the predominant circulating wild-type mumps strain (genotype G) were 6-fold lower than the GMTs against the Jeryl Lynn vaccine strain (genotype A). The majority of the participants (80%) received their second MMR vaccine ≥10 years prior to study participation. Additional efforts are needed to fully characterize B and T cell immune responses to mumps vaccine and to develop strategies to improve the quality and durability of vaccine-induced immunity.

scholarly journals Serological Study of Neutralizing Antibodies Against Enterovirus D68 Among Healthy Population in Xiamen, China

2020 ◽  
Author(s):  
Tong Cheng ◽  
Yu Lin ◽  
Rui Zhu ◽  
Yuanyuan Wu ◽  
Longfa Xu ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Age Groups ◽  
Neutralizing Antibody ◽  
Respiratory Illness ◽  
Risk Groups ◽  
Healthy Population ◽  
Serum Samples ◽  
Xiamen City ◽  
Enterovirus D68

Abstract Background: Enterovirus D68 (EV-D68) infections poses a serious public health threat, which caused outbreaks of severe respiratory illness and has been closely associated with "polio-like" central nervous system disease. The patterns of immune responses to EV-D68 have not been fully understood. This study was performed to investigate the level of neutralizing antibody against EV-D68 among the healthy population in Xiamen City.Methods: A total of 515 serum samples from healthy people were selected by stratified random sampling in Xiamen City in 2016, and the titer of neutralizing antibody against EV-D68 was detected by an efficient micro-neutralization assay.Results: The overall seroprevalence of neutralizing antibody against EV-D68 was 81.9%, and the overall geometric mean titers (GMT) was 248.0. The positive rates were 42.2%, 49.3%, 71.9%, 94.2% and 98.5%, respectively, in groups of <1, 1-3, 4-6, 7-19 and 20-39 years old, and were up to 100% in the 40-59 and ≥ 60 age groups. The GMTs in these seven groups were 1:39.8, 1:80.6, 1:133.2, 1:283.7, 1:253.3, 1:308.1 and 1:405.0, respectively. The seroprevalence and GMT of EV-D68 showed an increased trend with age, while gender and geographic area didn’t show significant impact.Conclusions: EV-D68 infection was prevalent in Xiamen City. Children are the high-risk groups for EV-D68-related illnesses, especially those aged ≤ 3 years. It is necessary to establish preventive measures and strengthened the surveillance on EV-D68 to prevent disease outbreaks.

scholarly journals A Reduced Dose Whole Virion Aluminum Adjuvanted Seasonal Influenza Vaccine Is Immunogenic, Safe, and Well Tolerated in Pediatric Patients

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 500
Author(s):  
Zoltan Vajo ◽  
Gergely Balaton ◽  
Peter Vajo ◽  
Peter Torzsa
Keyword(s):  
Pediatric Patients ◽  
Geometric Mean ◽  
Age Groups ◽  
Aluminum Phosphate ◽  
Vaccine Virus ◽  
Serious Adverse Events ◽  
Reduced Dose ◽  
Viral Hemagglutinin ◽  
Virus Strains ◽  
Two Age Groups

Background: Data suggest that pediatric patients might react differently to influenza vaccination, both in terms of immunity and side effects. We have recently shown that using a whole virion vaccine with aluminum phosphate adjuvants, reduced dose vaccines containing 6 µg of viral hemagglutinin (HA) per strain are immunogenic, and well tolerated in adult and elderly patients. Here we show the results of a multicenter clinical trial of pediatric patients, using reduced doses of a new, whole virion, aluminum phosphate adjuvanted vaccine (FluArt, Budapest, Hungary). Methods: A total of 120 healthy volunteers were included in two age groups (3–11 years, receiving 3 µg of HA per strain, and 12–18 years, receiving 6 µg of HA per strain). We used hemagglutination inhibition testing to assess immunogenicity, based on EMA and FDA licensing criteria, including post/pre-vaccination geometric mean titer ratios, seroconversion and seropositivity rates. Safety and tolerability were assessed using CHMP guidelines. Results: All subjects entered the study and were vaccinated (ITT population). All 120 subjects attended the control visit on Day 21 (PP population). All immunogenicity licensing criteria were met in both age groups for all three vaccine virus strains. No serious adverse events were detected and the vaccine was well tolerated by both age groups. Discussion: Using a whole virion vaccine and aluminum phosphate adjuvants, a reduction in the amount of the viral hemmaglutinin is possible while maintaining immunogenicity, safety and tolerability in pediatric and adolescent patients.

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