The Experts below are selected from a list of 18210 Experts worldwide ranked by ideXlab platform
Gregory M. Glenn - One of the best experts on this subject based on the ideXlab platform.
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safety and immunogenicity of a respiratory syncytial virus fusion f Protein Nanoparticle vaccine in healthy third trimester pregnant women and their infants
The Journal of Infectious Diseases, 2019Co-Authors: Flor M Muňoz, Pedro A Piedra, Somia P Hickman, Gregory M. Glenn, Geeta K Swamy, Sapeckshita Agrawal, Nita Patel, Allison August, Iksung Cho, Louis FriesAbstract:BACKGROUND Respiratory syncytial virus (RSV) is the leading cause of infant lower respiratory tract disease and hospitalization worldwide. METHODS Safety and immunogenicity of RSV fusion (F) Protein Nanoparticle vaccine or placebo were evaluated in 50 healthy third-trimester pregnant women. Assessments included vaccine tolerability and safety in women and infants, and RSV-specific antibody measures in women before and after vaccination, at delivery and post partum. RESULTS The vaccine was well tolerated; no meaningful differences in pregnancy or infant outcomes were observed between study groups. RSV-specific antibody levels increased significantly among vaccine recipients, including responses competitive with well-described monoclonal antibodies specific for multiple RSV neutralizing epitopes. No significant antibody increase was seen among placebo recipients, although a shallow upward trend across the RSV season was noted. Transplacental antibody transfer was 90%-120% across assays for infants of vaccinated women. Women with an interval of ≥30 days between vaccination and delivery demonstrated higher placental antibody transfer rates than women with an interval <30 days. Half-lives of RSV-specific antibodies in infants approximated 40 days. There was no evidence of severe RSV disease in infants of vaccinated mothers. CONCLUSIONS Data from this phase 2 study support a maternal immunization strategy to protect infants from RSV disease. CLINICAL TRIALS REGISTRATION NCT02247726.
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respiratory syncytial virus prefusogenic fusion f Protein Nanoparticle vaccine structure antigenic profile immunogenicity and protection
Vaccine, 2019Co-Authors: Nita Patel, Gregory M. Glenn, Haixia Zhou, Mike Massare, Jinghui Tian, Mimi Guebrexabier, Ernest L Maynard, Daniel Scott, Larry Ellingsworth, Gale SmithAbstract:Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in the very young, elderly, and immunocompromised for which there is no vaccine. The surface exposed RSV fusion (F) glycoProtein is required for membrane fusion and infection and is a desirable vaccine candidate. RSV F glycoProtein structure is dynamic and undergoes significant rearrangements during virus assembly, fusion, and infection. We have previously described an RSV fusion-inactive prefusogenic F with a mutation of one of two furin cleavage sites resulting in the p27 region on the N-terminus of F1 with a truncated fusion peptide covalently linked to F2. A processing intermediate RSV prefusogenic F has been reported in infected cells, purified F, budded virus, and elicited a strong immune response against p27 in RSV infected young children. In this report, we demonstrate that prefusogenic F, when expressed on the cell surface of Sf9 insect and human 293T cells, binds monoclonal antibodies (mAbs) that target prefusion-specific antigenic sites O and VIII, and mAbs targeting epitopes common to pre- and postfusion F sites II and IV. Purified prefusogenic F bound prefusion F specific mAbs to antigenic sites O and VIII and mAbs targeting pre- and postfusion sites II, IV, and p27. Mice immunized with prefusogenic F antigen produced significantly higher levels of anti-F IgG and RSV neutralizing antibodies than prefusion or postfusion F antigens and induced antibodies competitive with mAbs to sites O, VIII, II, and IV. RSV prefusogenic F neutralization antibody responses were enhanced with aluminum phosphate adjuvant and significantly higher than prefusion F. Prefusogenic F vaccine protected cotton rats against upper and lower respiratory tract infection by RSV/A. For the first time, we present the structure, antigenic profile, immunogenicity, and protective efficacy of RSV prefusogenic F Nanoparticle vaccine.
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immunogenicity and safety of a respiratory syncytial virus fusion Protein rsv f Nanoparticle vaccine in older adults
Immunity & Ageing, 2017Co-Authors: Louis Fries, Nigel D Thomas, Eloi Kpamegan, Pedro A Piedra, Somia P Hickman, Gale Smith, Vivek Shinde, Jeffrey J Stoddard, Gregory M. GlennAbstract:A preventative strategy for Respiratory Syncytial Virus (RSV) infection constitutes an under-recognized unmet medical need among older adults. Four formulations of a novel recombinant RSV F Nanoparticle vaccine (60 or 90 μg RSV F Protein, with or without aluminum phosphate adjuvant) administered concurrently with a licensed inactivated trivalent influenza vaccine (TIV) in older adult subjects were evaluated for safety and immunogenicity in this randomized, observer-blinded study. A total of 220 healthy males and females ≥ 60 years of age, without symptomatic cardiopulmonary disease, were vaccinated concurrently with TIV and RSV F vaccine or placebo. All vaccine formulations produced an acceptable safety profile, with no vaccine-related serious adverse events or evidence of systemic toxicity. Vaccine-induced immune responses were rapid, rising as early as 7 days post-vaccination; and were comparable in all formulations in terms of magnitude, with maximal levels attained within 28 (unadjuvanted) or 56 (adjuvanted) days post-vaccination. Peak anti-F Protein IgG antibody levels rose 3.6- to 5.6-fold, with an adjuvant effect observed at the 60 μg dose, and a dose-effect observed between the unadjuvanted 60 and 90 μg regimens. The anti-F response persisted through 12 months post-vaccination. Palivizumab-competitive antibodies were below quantifiable levels (<33 μg/mL) at day 0. The rise of antibodies with specificity for Site II peptide, and the palivizumab-competitive binding activity, denoting antibodies binding at, or in proximity to, antigenic Site II on the F Protein, closely paralleled the anti-F response. However, a larger proportion of antibodies in adjuvanted vaccine recipients bound to the Site II peptide at high avidity. Day 0 neutralizing antibodies were high in all subjects and rose 1.3- to 1.7-fold in response to vaccination. Importantly, the RSV F vaccine co-administered with TIV did not impact the serum hemagglutination inhibition antibody responses to a standard-dose TIV, and TIV did not impact the immune response to the RSV F vaccine. RSV F Protein Nanoparticle vaccine induced increases in measures of functional immunity to RSV in older adults and demonstrated an acceptable safety profile. Adjuvanted formulations provided additional immunogenicity benefit as compared to increasing antigen dose alone. This trial was registered with ClinicalTrials.gov number NCT01709019.
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a randomized blinded controlled dose ranging study of a respiratory syncytial virus recombinant fusion f Nanoparticle vaccine in healthy women of childbearing age
The Journal of Infectious Diseases, 2016Co-Authors: Gregory M. Glenn, Louis F Fries, Nigel D Thomas, Eloi Kpamegan, David Flyer, Dewal Jani, Somia P Hickman, Hanxin Lu, Gale Smith, Pedro A PiedraAbstract:Background. Respiratory syncytial virus (RSV) is a leading cause of infant morbidity and mortality. A recombinant RSV fusion Protein Nanoparticle vaccine (RSV F vaccine) candidate for maternal immunization was tested for safety and immunogenicity in women of childbearing age. Methods. Three hundred thirty women (18–35 years) were randomized to receive 1 or 2 doses of RSV F vaccine (60 or 90 µg) with or without aluminum phosphate adjuvant, or placebo at days 0 and 28. Safety was evaluated over 180 days; immunogenicity and RSV infection rates were evaluated over 112 days. Results. All vaccine formulations were well tolerated, without vaccine-related serious adverse events. Anti-F immunoglobulin G antibodies rose 6.5–15.6-fold, with significantly higher levels in 2-dose, adjuvanted regimens at day 56. Palivizumab-competitive antibody levels were undetectable at day 0 but increased up to 325 µg/mL at day 56. A 2.7- and 3.5-fold rise in RSV/A and RSV/ B microneutralization antibodies were noted at day 56. Between days 56 and 112, 21% (12/56) of placebo recipients and 11% of vaccinees (26/244) showed evidence of a recent RSV infection (P= .04). Conclusions. The vaccine appeared safe, immunogenic, and reduced RSV infections. Further development as avaccine for use in maternal immunization is warranted. Clinical Trials Registration. NCT01704365.
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safety and immunogenicity of a sf9 insect cell derived respiratory syncytial virus fusion Protein Nanoparticle vaccine
Vaccine, 2013Co-Authors: Gregory M. Glenn, Nigel D Thomas, Eloi Kpamegan, Somia P Hickman, Gale Smith, Louis Fries, Rama Raghunandan, Bin Zhou, Sarathi Boddapati, Pedro A PiedraAbstract:Abstract Objective We performed a Phase 1 randomized, observer-blinded, placebo-controlled trial to evaluate the safety and immunogenicity of a recombinant respiratory syncytial virus (RSV) fusion (F) Protein Nanoparticle vaccine. Methods Six formulations with (5, 15, 30 and 60 μg) and without (30 and 60 μg) aluminum phosphate (AdjuPhos) were administered intramuscularly on day 0 and 30 in a dose escalating fashion to healthy adults 18–49 years of age. Solicited and unsolicited events were collected through day 210. Immunogenicity measures taken at day 0, 30 and 60 included RSV A and B microneutralization, anti-F IgG, antigenic site II peptide and palivizumab competitive antibodies. Results The vaccine was well-tolerated, with no evident dose-related toxicity or attributable SAEs. At day 60 both RSV A and B microneutralization was significantly increased in vaccinees versus placebo. Across all vaccinees there was a 7- to 19-fold increase in the anti-F IgG and a 7- to 24-fold increase in the antigenic site II binding and palivizumab competitive antibodies. Conclusions The RSV F Nanoparticle vaccine candidate was well tolerated without dose-related increases in adverse events. Measures of immunity indicate that neutralization, anti-RSV F IgG titers and palivizumab competing antibodies were induced at levels that have been associated with decreased risk of hospitalization. NCT01290419 .
Jun Guo - One of the best experts on this subject based on the ideXlab platform.
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intracellular ion and Protein Nanoparticle induced osmotic pressure modify astrocyte swelling and brain edema in response to glutamate stimuli
Redox biology, 2019Co-Authors: Jiarui Zhang, Yuxuan Wang, Zihui Zheng, Xiaohe Sun, Tingting Chen, Xiaolong Zhang, Jun GuoAbstract:Abstract Intracellular tension activity plays a crucial role in cytotoxic brain edema and astrocyte swelling. Here, a few genetically encoded FRET-based tension probes were designed to detect cytoskeletal structural tension optically, including their magnitude and vectors. The astrocyte swelling resulted in GFAP tension increment, which is associated with the antagonistic effect of inward microfilaments (MFs) and microtubules (MTs) forces. In glutamate-induced astrocyte swelling, GFAP tension rise resulted from outward ion and Protein Nanoparticle-induced osmotic pressure (PN-OP) increases, where PN-OP could be elicited by MF and MT depolymerization, Protein Nanoparticle production, and activation of cofilin and stathmin-1. Attenuation of both ion osmotic pressure and PN-OP by drug combinations, together with free-radical scavenger, relieved cerebral edema in vivo. The study suggests that intracellular osmotic pressure (especially PN-OP) has a pivotal role in glutamate-induced astrocyte swelling and brain edema. Recovery of cytoplasmic potential is a promising target to develop new drugs and cure brain edema.
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Intracellular ion and Protein Nanoparticle-induced osmotic pressure modify astrocyte swelling and brain edema in response to glutamate stimuli
Elsevier, 2019Co-Authors: Jiarui Zhang, Yuxuan Wang, Zihui Zheng, Xiaohe Sun, Tingting Chen, Xiaolong Zhang, Jun GuoAbstract:Intracellular tension activity plays a crucial role in cytotoxic brain edema and astrocyte swelling. Here, a few genetically encoded FRET-based tension probes were designed to detect cytoskeletal structural tension optically, including their magnitude and vectors. The astrocyte swelling resulted in GFAP tension increment, which is associated with the antagonistic effect of inward microfilaments (MFs) and microtubules (MTs) forces. In glutamate-induced astrocyte swelling, GFAP tension rise resulted from outward ion and Protein Nanoparticle-induced osmotic pressure (PN-OP) increases, where PN-OP could be elicited by MF and MT depolymerization, Protein Nanoparticle production, and activation of cofilin and stathmin-1. Attenuation of both ion osmotic pressure and PN-OP by drug combinations, together with free-radical scavenger, relieved cerebral edema in vivo. The study suggests that intracellular osmotic pressure (especially PN-OP) has a pivotal role in glutamate-induced astrocyte swelling and brain edema. Recovery of cytoplasmic potential is a promising target to develop new drugs and cure brain edema. Keywords: Brain edema, Astrocyte, Glutamate, Protein Nanoparticle-induced osmotic pressure, GFAP tension prob
Pedro A Piedra - One of the best experts on this subject based on the ideXlab platform.
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safety and immunogenicity of a respiratory syncytial virus fusion f Protein Nanoparticle vaccine in healthy third trimester pregnant women and their infants
The Journal of Infectious Diseases, 2019Co-Authors: Flor M Muňoz, Pedro A Piedra, Somia P Hickman, Gregory M. Glenn, Geeta K Swamy, Sapeckshita Agrawal, Nita Patel, Allison August, Iksung Cho, Louis FriesAbstract:BACKGROUND Respiratory syncytial virus (RSV) is the leading cause of infant lower respiratory tract disease and hospitalization worldwide. METHODS Safety and immunogenicity of RSV fusion (F) Protein Nanoparticle vaccine or placebo were evaluated in 50 healthy third-trimester pregnant women. Assessments included vaccine tolerability and safety in women and infants, and RSV-specific antibody measures in women before and after vaccination, at delivery and post partum. RESULTS The vaccine was well tolerated; no meaningful differences in pregnancy or infant outcomes were observed between study groups. RSV-specific antibody levels increased significantly among vaccine recipients, including responses competitive with well-described monoclonal antibodies specific for multiple RSV neutralizing epitopes. No significant antibody increase was seen among placebo recipients, although a shallow upward trend across the RSV season was noted. Transplacental antibody transfer was 90%-120% across assays for infants of vaccinated women. Women with an interval of ≥30 days between vaccination and delivery demonstrated higher placental antibody transfer rates than women with an interval <30 days. Half-lives of RSV-specific antibodies in infants approximated 40 days. There was no evidence of severe RSV disease in infants of vaccinated mothers. CONCLUSIONS Data from this phase 2 study support a maternal immunization strategy to protect infants from RSV disease. CLINICAL TRIALS REGISTRATION NCT02247726.
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immunogenicity and safety of a respiratory syncytial virus fusion Protein rsv f Nanoparticle vaccine in older adults
Immunity & Ageing, 2017Co-Authors: Louis Fries, Nigel D Thomas, Eloi Kpamegan, Pedro A Piedra, Somia P Hickman, Gale Smith, Vivek Shinde, Jeffrey J Stoddard, Gregory M. GlennAbstract:A preventative strategy for Respiratory Syncytial Virus (RSV) infection constitutes an under-recognized unmet medical need among older adults. Four formulations of a novel recombinant RSV F Nanoparticle vaccine (60 or 90 μg RSV F Protein, with or without aluminum phosphate adjuvant) administered concurrently with a licensed inactivated trivalent influenza vaccine (TIV) in older adult subjects were evaluated for safety and immunogenicity in this randomized, observer-blinded study. A total of 220 healthy males and females ≥ 60 years of age, without symptomatic cardiopulmonary disease, were vaccinated concurrently with TIV and RSV F vaccine or placebo. All vaccine formulations produced an acceptable safety profile, with no vaccine-related serious adverse events or evidence of systemic toxicity. Vaccine-induced immune responses were rapid, rising as early as 7 days post-vaccination; and were comparable in all formulations in terms of magnitude, with maximal levels attained within 28 (unadjuvanted) or 56 (adjuvanted) days post-vaccination. Peak anti-F Protein IgG antibody levels rose 3.6- to 5.6-fold, with an adjuvant effect observed at the 60 μg dose, and a dose-effect observed between the unadjuvanted 60 and 90 μg regimens. The anti-F response persisted through 12 months post-vaccination. Palivizumab-competitive antibodies were below quantifiable levels (<33 μg/mL) at day 0. The rise of antibodies with specificity for Site II peptide, and the palivizumab-competitive binding activity, denoting antibodies binding at, or in proximity to, antigenic Site II on the F Protein, closely paralleled the anti-F response. However, a larger proportion of antibodies in adjuvanted vaccine recipients bound to the Site II peptide at high avidity. Day 0 neutralizing antibodies were high in all subjects and rose 1.3- to 1.7-fold in response to vaccination. Importantly, the RSV F vaccine co-administered with TIV did not impact the serum hemagglutination inhibition antibody responses to a standard-dose TIV, and TIV did not impact the immune response to the RSV F vaccine. RSV F Protein Nanoparticle vaccine induced increases in measures of functional immunity to RSV in older adults and demonstrated an acceptable safety profile. Adjuvanted formulations provided additional immunogenicity benefit as compared to increasing antigen dose alone. This trial was registered with ClinicalTrials.gov number NCT01709019.
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a randomized blinded controlled dose ranging study of a respiratory syncytial virus recombinant fusion f Nanoparticle vaccine in healthy women of childbearing age
The Journal of Infectious Diseases, 2016Co-Authors: Gregory M. Glenn, Louis F Fries, Nigel D Thomas, Eloi Kpamegan, David Flyer, Dewal Jani, Somia P Hickman, Hanxin Lu, Gale Smith, Pedro A PiedraAbstract:Background. Respiratory syncytial virus (RSV) is a leading cause of infant morbidity and mortality. A recombinant RSV fusion Protein Nanoparticle vaccine (RSV F vaccine) candidate for maternal immunization was tested for safety and immunogenicity in women of childbearing age. Methods. Three hundred thirty women (18–35 years) were randomized to receive 1 or 2 doses of RSV F vaccine (60 or 90 µg) with or without aluminum phosphate adjuvant, or placebo at days 0 and 28. Safety was evaluated over 180 days; immunogenicity and RSV infection rates were evaluated over 112 days. Results. All vaccine formulations were well tolerated, without vaccine-related serious adverse events. Anti-F immunoglobulin G antibodies rose 6.5–15.6-fold, with significantly higher levels in 2-dose, adjuvanted regimens at day 56. Palivizumab-competitive antibody levels were undetectable at day 0 but increased up to 325 µg/mL at day 56. A 2.7- and 3.5-fold rise in RSV/A and RSV/ B microneutralization antibodies were noted at day 56. Between days 56 and 112, 21% (12/56) of placebo recipients and 11% of vaccinees (26/244) showed evidence of a recent RSV infection (P= .04). Conclusions. The vaccine appeared safe, immunogenic, and reduced RSV infections. Further development as avaccine for use in maternal immunization is warranted. Clinical Trials Registration. NCT01704365.
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safety and immunogenicity of a sf9 insect cell derived respiratory syncytial virus fusion Protein Nanoparticle vaccine
Vaccine, 2013Co-Authors: Gregory M. Glenn, Nigel D Thomas, Eloi Kpamegan, Somia P Hickman, Gale Smith, Louis Fries, Rama Raghunandan, Bin Zhou, Sarathi Boddapati, Pedro A PiedraAbstract:Abstract Objective We performed a Phase 1 randomized, observer-blinded, placebo-controlled trial to evaluate the safety and immunogenicity of a recombinant respiratory syncytial virus (RSV) fusion (F) Protein Nanoparticle vaccine. Methods Six formulations with (5, 15, 30 and 60 μg) and without (30 and 60 μg) aluminum phosphate (AdjuPhos) were administered intramuscularly on day 0 and 30 in a dose escalating fashion to healthy adults 18–49 years of age. Solicited and unsolicited events were collected through day 210. Immunogenicity measures taken at day 0, 30 and 60 included RSV A and B microneutralization, anti-F IgG, antigenic site II peptide and palivizumab competitive antibodies. Results The vaccine was well-tolerated, with no evident dose-related toxicity or attributable SAEs. At day 60 both RSV A and B microneutralization was significantly increased in vaccinees versus placebo. Across all vaccinees there was a 7- to 19-fold increase in the anti-F IgG and a 7- to 24-fold increase in the antigenic site II binding and palivizumab competitive antibodies. Conclusions The RSV F Nanoparticle vaccine candidate was well tolerated without dose-related increases in adverse events. Measures of immunity indicate that neutralization, anti-RSV F IgG titers and palivizumab competing antibodies were induced at levels that have been associated with decreased risk of hospitalization. NCT01290419 .
Gale Smith - One of the best experts on this subject based on the ideXlab platform.
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respiratory syncytial virus prefusogenic fusion f Protein Nanoparticle vaccine structure antigenic profile immunogenicity and protection
Vaccine, 2019Co-Authors: Nita Patel, Gregory M. Glenn, Haixia Zhou, Mike Massare, Jinghui Tian, Mimi Guebrexabier, Ernest L Maynard, Daniel Scott, Larry Ellingsworth, Gale SmithAbstract:Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in the very young, elderly, and immunocompromised for which there is no vaccine. The surface exposed RSV fusion (F) glycoProtein is required for membrane fusion and infection and is a desirable vaccine candidate. RSV F glycoProtein structure is dynamic and undergoes significant rearrangements during virus assembly, fusion, and infection. We have previously described an RSV fusion-inactive prefusogenic F with a mutation of one of two furin cleavage sites resulting in the p27 region on the N-terminus of F1 with a truncated fusion peptide covalently linked to F2. A processing intermediate RSV prefusogenic F has been reported in infected cells, purified F, budded virus, and elicited a strong immune response against p27 in RSV infected young children. In this report, we demonstrate that prefusogenic F, when expressed on the cell surface of Sf9 insect and human 293T cells, binds monoclonal antibodies (mAbs) that target prefusion-specific antigenic sites O and VIII, and mAbs targeting epitopes common to pre- and postfusion F sites II and IV. Purified prefusogenic F bound prefusion F specific mAbs to antigenic sites O and VIII and mAbs targeting pre- and postfusion sites II, IV, and p27. Mice immunized with prefusogenic F antigen produced significantly higher levels of anti-F IgG and RSV neutralizing antibodies than prefusion or postfusion F antigens and induced antibodies competitive with mAbs to sites O, VIII, II, and IV. RSV prefusogenic F neutralization antibody responses were enhanced with aluminum phosphate adjuvant and significantly higher than prefusion F. Prefusogenic F vaccine protected cotton rats against upper and lower respiratory tract infection by RSV/A. For the first time, we present the structure, antigenic profile, immunogenicity, and protective efficacy of RSV prefusogenic F Nanoparticle vaccine.
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immunogenicity and safety of a respiratory syncytial virus fusion Protein rsv f Nanoparticle vaccine in older adults
Immunity & Ageing, 2017Co-Authors: Louis Fries, Nigel D Thomas, Eloi Kpamegan, Pedro A Piedra, Somia P Hickman, Gale Smith, Vivek Shinde, Jeffrey J Stoddard, Gregory M. GlennAbstract:A preventative strategy for Respiratory Syncytial Virus (RSV) infection constitutes an under-recognized unmet medical need among older adults. Four formulations of a novel recombinant RSV F Nanoparticle vaccine (60 or 90 μg RSV F Protein, with or without aluminum phosphate adjuvant) administered concurrently with a licensed inactivated trivalent influenza vaccine (TIV) in older adult subjects were evaluated for safety and immunogenicity in this randomized, observer-blinded study. A total of 220 healthy males and females ≥ 60 years of age, without symptomatic cardiopulmonary disease, were vaccinated concurrently with TIV and RSV F vaccine or placebo. All vaccine formulations produced an acceptable safety profile, with no vaccine-related serious adverse events or evidence of systemic toxicity. Vaccine-induced immune responses were rapid, rising as early as 7 days post-vaccination; and were comparable in all formulations in terms of magnitude, with maximal levels attained within 28 (unadjuvanted) or 56 (adjuvanted) days post-vaccination. Peak anti-F Protein IgG antibody levels rose 3.6- to 5.6-fold, with an adjuvant effect observed at the 60 μg dose, and a dose-effect observed between the unadjuvanted 60 and 90 μg regimens. The anti-F response persisted through 12 months post-vaccination. Palivizumab-competitive antibodies were below quantifiable levels (<33 μg/mL) at day 0. The rise of antibodies with specificity for Site II peptide, and the palivizumab-competitive binding activity, denoting antibodies binding at, or in proximity to, antigenic Site II on the F Protein, closely paralleled the anti-F response. However, a larger proportion of antibodies in adjuvanted vaccine recipients bound to the Site II peptide at high avidity. Day 0 neutralizing antibodies were high in all subjects and rose 1.3- to 1.7-fold in response to vaccination. Importantly, the RSV F vaccine co-administered with TIV did not impact the serum hemagglutination inhibition antibody responses to a standard-dose TIV, and TIV did not impact the immune response to the RSV F vaccine. RSV F Protein Nanoparticle vaccine induced increases in measures of functional immunity to RSV in older adults and demonstrated an acceptable safety profile. Adjuvanted formulations provided additional immunogenicity benefit as compared to increasing antigen dose alone. This trial was registered with ClinicalTrials.gov number NCT01709019.
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a randomized blinded controlled dose ranging study of a respiratory syncytial virus recombinant fusion f Nanoparticle vaccine in healthy women of childbearing age
The Journal of Infectious Diseases, 2016Co-Authors: Gregory M. Glenn, Louis F Fries, Nigel D Thomas, Eloi Kpamegan, David Flyer, Dewal Jani, Somia P Hickman, Hanxin Lu, Gale Smith, Pedro A PiedraAbstract:Background. Respiratory syncytial virus (RSV) is a leading cause of infant morbidity and mortality. A recombinant RSV fusion Protein Nanoparticle vaccine (RSV F vaccine) candidate for maternal immunization was tested for safety and immunogenicity in women of childbearing age. Methods. Three hundred thirty women (18–35 years) were randomized to receive 1 or 2 doses of RSV F vaccine (60 or 90 µg) with or without aluminum phosphate adjuvant, or placebo at days 0 and 28. Safety was evaluated over 180 days; immunogenicity and RSV infection rates were evaluated over 112 days. Results. All vaccine formulations were well tolerated, without vaccine-related serious adverse events. Anti-F immunoglobulin G antibodies rose 6.5–15.6-fold, with significantly higher levels in 2-dose, adjuvanted regimens at day 56. Palivizumab-competitive antibody levels were undetectable at day 0 but increased up to 325 µg/mL at day 56. A 2.7- and 3.5-fold rise in RSV/A and RSV/ B microneutralization antibodies were noted at day 56. Between days 56 and 112, 21% (12/56) of placebo recipients and 11% of vaccinees (26/244) showed evidence of a recent RSV infection (P= .04). Conclusions. The vaccine appeared safe, immunogenic, and reduced RSV infections. Further development as avaccine for use in maternal immunization is warranted. Clinical Trials Registration. NCT01704365.
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safety and immunogenicity of a sf9 insect cell derived respiratory syncytial virus fusion Protein Nanoparticle vaccine
Vaccine, 2013Co-Authors: Gregory M. Glenn, Nigel D Thomas, Eloi Kpamegan, Somia P Hickman, Gale Smith, Louis Fries, Rama Raghunandan, Bin Zhou, Sarathi Boddapati, Pedro A PiedraAbstract:Abstract Objective We performed a Phase 1 randomized, observer-blinded, placebo-controlled trial to evaluate the safety and immunogenicity of a recombinant respiratory syncytial virus (RSV) fusion (F) Protein Nanoparticle vaccine. Methods Six formulations with (5, 15, 30 and 60 μg) and without (30 and 60 μg) aluminum phosphate (AdjuPhos) were administered intramuscularly on day 0 and 30 in a dose escalating fashion to healthy adults 18–49 years of age. Solicited and unsolicited events were collected through day 210. Immunogenicity measures taken at day 0, 30 and 60 included RSV A and B microneutralization, anti-F IgG, antigenic site II peptide and palivizumab competitive antibodies. Results The vaccine was well-tolerated, with no evident dose-related toxicity or attributable SAEs. At day 60 both RSV A and B microneutralization was significantly increased in vaccinees versus placebo. Across all vaccinees there was a 7- to 19-fold increase in the anti-F IgG and a 7- to 24-fold increase in the antigenic site II binding and palivizumab competitive antibodies. Conclusions The RSV F Nanoparticle vaccine candidate was well tolerated without dose-related increases in adverse events. Measures of immunity indicate that neutralization, anti-RSV F IgG titers and palivizumab competing antibodies were induced at levels that have been associated with decreased risk of hospitalization. NCT01290419 .
Louis Fries - One of the best experts on this subject based on the ideXlab platform.
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safety and immunogenicity of a respiratory syncytial virus fusion f Protein Nanoparticle vaccine in healthy third trimester pregnant women and their infants
The Journal of Infectious Diseases, 2019Co-Authors: Flor M Muňoz, Pedro A Piedra, Somia P Hickman, Gregory M. Glenn, Geeta K Swamy, Sapeckshita Agrawal, Nita Patel, Allison August, Iksung Cho, Louis FriesAbstract:BACKGROUND Respiratory syncytial virus (RSV) is the leading cause of infant lower respiratory tract disease and hospitalization worldwide. METHODS Safety and immunogenicity of RSV fusion (F) Protein Nanoparticle vaccine or placebo were evaluated in 50 healthy third-trimester pregnant women. Assessments included vaccine tolerability and safety in women and infants, and RSV-specific antibody measures in women before and after vaccination, at delivery and post partum. RESULTS The vaccine was well tolerated; no meaningful differences in pregnancy or infant outcomes were observed between study groups. RSV-specific antibody levels increased significantly among vaccine recipients, including responses competitive with well-described monoclonal antibodies specific for multiple RSV neutralizing epitopes. No significant antibody increase was seen among placebo recipients, although a shallow upward trend across the RSV season was noted. Transplacental antibody transfer was 90%-120% across assays for infants of vaccinated women. Women with an interval of ≥30 days between vaccination and delivery demonstrated higher placental antibody transfer rates than women with an interval <30 days. Half-lives of RSV-specific antibodies in infants approximated 40 days. There was no evidence of severe RSV disease in infants of vaccinated mothers. CONCLUSIONS Data from this phase 2 study support a maternal immunization strategy to protect infants from RSV disease. CLINICAL TRIALS REGISTRATION NCT02247726.
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immunogenicity and safety of a respiratory syncytial virus fusion Protein rsv f Nanoparticle vaccine in older adults
Immunity & Ageing, 2017Co-Authors: Louis Fries, Nigel D Thomas, Eloi Kpamegan, Pedro A Piedra, Somia P Hickman, Gale Smith, Vivek Shinde, Jeffrey J Stoddard, Gregory M. GlennAbstract:A preventative strategy for Respiratory Syncytial Virus (RSV) infection constitutes an under-recognized unmet medical need among older adults. Four formulations of a novel recombinant RSV F Nanoparticle vaccine (60 or 90 μg RSV F Protein, with or without aluminum phosphate adjuvant) administered concurrently with a licensed inactivated trivalent influenza vaccine (TIV) in older adult subjects were evaluated for safety and immunogenicity in this randomized, observer-blinded study. A total of 220 healthy males and females ≥ 60 years of age, without symptomatic cardiopulmonary disease, were vaccinated concurrently with TIV and RSV F vaccine or placebo. All vaccine formulations produced an acceptable safety profile, with no vaccine-related serious adverse events or evidence of systemic toxicity. Vaccine-induced immune responses were rapid, rising as early as 7 days post-vaccination; and were comparable in all formulations in terms of magnitude, with maximal levels attained within 28 (unadjuvanted) or 56 (adjuvanted) days post-vaccination. Peak anti-F Protein IgG antibody levels rose 3.6- to 5.6-fold, with an adjuvant effect observed at the 60 μg dose, and a dose-effect observed between the unadjuvanted 60 and 90 μg regimens. The anti-F response persisted through 12 months post-vaccination. Palivizumab-competitive antibodies were below quantifiable levels (<33 μg/mL) at day 0. The rise of antibodies with specificity for Site II peptide, and the palivizumab-competitive binding activity, denoting antibodies binding at, or in proximity to, antigenic Site II on the F Protein, closely paralleled the anti-F response. However, a larger proportion of antibodies in adjuvanted vaccine recipients bound to the Site II peptide at high avidity. Day 0 neutralizing antibodies were high in all subjects and rose 1.3- to 1.7-fold in response to vaccination. Importantly, the RSV F vaccine co-administered with TIV did not impact the serum hemagglutination inhibition antibody responses to a standard-dose TIV, and TIV did not impact the immune response to the RSV F vaccine. RSV F Protein Nanoparticle vaccine induced increases in measures of functional immunity to RSV in older adults and demonstrated an acceptable safety profile. Adjuvanted formulations provided additional immunogenicity benefit as compared to increasing antigen dose alone. This trial was registered with ClinicalTrials.gov number NCT01709019.
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safety and immunogenicity of a sf9 insect cell derived respiratory syncytial virus fusion Protein Nanoparticle vaccine
Vaccine, 2013Co-Authors: Gregory M. Glenn, Nigel D Thomas, Eloi Kpamegan, Somia P Hickman, Gale Smith, Louis Fries, Rama Raghunandan, Bin Zhou, Sarathi Boddapati, Pedro A PiedraAbstract:Abstract Objective We performed a Phase 1 randomized, observer-blinded, placebo-controlled trial to evaluate the safety and immunogenicity of a recombinant respiratory syncytial virus (RSV) fusion (F) Protein Nanoparticle vaccine. Methods Six formulations with (5, 15, 30 and 60 μg) and without (30 and 60 μg) aluminum phosphate (AdjuPhos) were administered intramuscularly on day 0 and 30 in a dose escalating fashion to healthy adults 18–49 years of age. Solicited and unsolicited events were collected through day 210. Immunogenicity measures taken at day 0, 30 and 60 included RSV A and B microneutralization, anti-F IgG, antigenic site II peptide and palivizumab competitive antibodies. Results The vaccine was well-tolerated, with no evident dose-related toxicity or attributable SAEs. At day 60 both RSV A and B microneutralization was significantly increased in vaccinees versus placebo. Across all vaccinees there was a 7- to 19-fold increase in the anti-F IgG and a 7- to 24-fold increase in the antigenic site II binding and palivizumab competitive antibodies. Conclusions The RSV F Nanoparticle vaccine candidate was well tolerated without dose-related increases in adverse events. Measures of immunity indicate that neutralization, anti-RSV F IgG titers and palivizumab competing antibodies were induced at levels that have been associated with decreased risk of hospitalization. NCT01290419 .
