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Elizabeth Schappell - One of the best experts on this subject based on the ideXlab platform.
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live attenuated respiratory syncytial virus vaccine with M2 2 deletion and with small hydrophobic noncoding region is highly immunogenic in children
The Journal of Infectious Diseases, 2020Co-Authors: Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Coleen K Cunningham, Charlotte Perlowski, Jennifer Libous, Jack Moye, Jennifer Oliva, Patrick Jeanphilippe, Elizabeth SchappellAbstract:BACKGROUND Respiratory syncytial virus (RSV) is the leading viral cause of severe pediatric respiratory illness, and vaccines are needed. Live RSV vaccine D46/NS2/N/ΔM2-2-HindIII, attenuated by deletion of the RSV RNA regulatory Protein M2-2, is based on previous candidate LID/ΔM2-2 but incorporates prominent differences from MEDI/ΔM2-2, which was more restricted in replication in phase 1. METHODS RSV-seronegative children aged 6-24 months received 1 intranasal dose (105 plaque-forming units [PFUs] of D46/NS2/N/ΔM2-2-HindIII [n = 21] or placebo [n = 11]) and were monitored for vaccine shedding, reactogenicity, RSV-antibody responses and RSV-associated medically attended acute respiratory illness (RSV-MAARI) and antibody responses during the following RSV season. RESULTS All 21 vaccinees were infected with vaccine; 20 (95%) shed vaccine (median peak titer, 3.5 log10 PFUs/mL with immunoplaque assay and 6.1 log10 copies/mL with polymerase chain reaction). Serum RSV-neutralizing antibodies and anti-RSV fusion immunoglobulin G increased ≥4-fold in 95% and 100% of vaccines, respectively. Mild upper respiratory tract symptoms and/or fever occurred in vaccinees (76%) and placebo recipients (18%). Over the RSV season, RSV-MAARI occurred in 2 vaccinees and 4 placebo recipients. Three vaccinees had ≥4-fold increases in serum RSV-neutralizing antibody titers after the RSV season without RSV-MAARI. CONCLUSIONS D46/NS2/N/ΔM2-2-HindIII had excellent infectivity and immunogenicity and primed vaccine recipients for anamnestic responses, encouraging further evaluation of this attenuation strategy. CLINICAL TRIALS REGISTRATION NCT03102034 and NCT03099291.
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live respiratory syncytial virus attenuated by M2 2 deletion and stabilized temperature sensitivity mutation 1030s is a promising vaccine candidate in children
The Journal of Infectious Diseases, 2020Co-Authors: Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Coleen K Cunningham, Charlotte Perlowski, Bhagvanji Thumar, Devasena Gnanashanmugam, Jennifer Libous, Jack Moye, Elizabeth SchappellAbstract:Background The safety and immunogenicity of live respiratory syncytial virus (RSV) candidate vaccine, LID/ΔM2-2/1030s, with deletion of RSV ribonucleic acid synthesis regulatory Protein M2-2 and genetically stabilized temperature-sensitivity mutation 1030s in the RSV polymerase Protein was evaluated in RSV-seronegative children. Methods Respiratory syncytial virus-seronegative children ages 6-24 months received 1 intranasal dose of 105 plaque-forming units (PFU) of LID/ΔM2-2/1030s (n = 21) or placebo (n = 11). The RSV serum antibodies, vaccine shedding, and reactogenicity were assessed. During the following RSV season, medically attended acute respiratory illness (MAARI) and pre- and postsurveillance serum antibody titers were monitored. Results Eighty-five percent of vaccinees shed LID/ΔM2-2/1030s vaccine (median peak nasal wash titers: 3.1 log10 PFU/mL by immunoplaque assay; 5.1 log10 copies/mL by reverse-transcription quantitative polymerase chain reaction) and had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms and fever were common (60% vaccinees and 27% placebo recipients). One vaccinee had grade 2 wheezing with rhinovirus but without concurrent LID/ΔM2-2/1030s shedding. Five of 19 vaccinees had ≥4-fold increases in antibody titers postsurveillance without RSV-MAARI, indicating anamnestic responses without significant illness after infection with community-acquired RSV. Conclusions LID/ΔM2-2/1030s had excellent infectivity without evidence of genetic instability, induced durable immunity, and primed for anamnestic antibody responses, making it an attractive candidate for further evaluation.
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live attenuated respiratory syncytial virus vaccine with deletion of rna synthesis regulatory Protein M2 2 and cold passage mutations is overattenuated
Open Forum Infectious Diseases, 2019Co-Authors: Coleen K Cunningham, Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Charlotte Perlowski, Bhagvanji Thumar, Devasena Gnanashanmugam, Jennifer Libous, Jack Moye, Elizabeth SchappellAbstract:Background The live respiratory syncytial virus (RSV) candidate vaccine LIDcpΔM2-2 is attenuated through deletion of M2-2 and 5 cold-passage mutations. Methods RSV-seronegative children aged 6-24 months received a single intranasal dose of 105 plaque-forming units (PFU) of LIDcpΔM2-2 or placebo. RSV serum antibodies, vaccine infectivity, and reactogenicity were assessed. Results Four of 11 (36%) vaccinees shed vaccine virus with median peak titers of 1.6 log10 PFU/mL by quantitative culture and 4.5 log10 copies/mL by polymerase chain reaction; 45% had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms or fever were common in vaccinees (64%) and placebo recipients (6/6, 100%). Conclusions RSV LIDcpΔM2-2 is overattenuated. Clinical Trial Numbers. NCT02890381, NCT02948127.
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live attenuated respiratory syncytial virus vaccine with deletion of rna synthesis regulatory Protein M2 2 and cold passage mutations is overattenuated
Open Forum Infectious Diseases, 2019Co-Authors: Coleen K Cunningham, Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Charlotte Perlowski, Bhagvanji Thumar, Devasena Gnanashanmugam, Jennifer Libous, Jack Moye, Elizabeth SchappellAbstract:Background The live respiratory syncytial virus (RSV) candidate vaccine LIDcpΔM2-2 is attenuated through deletion of M2-2 and 5 cold-passage mutations.
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live attenuated respiratory syncytial virus vaccine candidate with deletion of rna synthesis regulatory Protein M2 2 is highly immunogenic in children
The Journal of Infectious Diseases, 2018Co-Authors: Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Coleen K Cunningham, Megan Valentine, Charlotte Perlowski, Bhagvanji Thumar, Devasena Gnanashanmugam, George K Siberry, Elizabeth SchappellAbstract:Background Live respiratory syncytial virus (RSV) candidate vaccine LIDΔM2-2 is attenuated by deletion of the RSV RNA regulatory Protein M2-2, resulting in upregulated viral gene transcription and antigen expression but reduced RNA replication.
Elizabeth J Mcfarland - One of the best experts on this subject based on the ideXlab platform.
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live attenuated respiratory syncytial virus vaccine with M2 2 deletion and with small hydrophobic noncoding region is highly immunogenic in children
The Journal of Infectious Diseases, 2020Co-Authors: Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Coleen K Cunningham, Charlotte Perlowski, Jennifer Libous, Jack Moye, Jennifer Oliva, Patrick Jeanphilippe, Elizabeth SchappellAbstract:BACKGROUND Respiratory syncytial virus (RSV) is the leading viral cause of severe pediatric respiratory illness, and vaccines are needed. Live RSV vaccine D46/NS2/N/ΔM2-2-HindIII, attenuated by deletion of the RSV RNA regulatory Protein M2-2, is based on previous candidate LID/ΔM2-2 but incorporates prominent differences from MEDI/ΔM2-2, which was more restricted in replication in phase 1. METHODS RSV-seronegative children aged 6-24 months received 1 intranasal dose (105 plaque-forming units [PFUs] of D46/NS2/N/ΔM2-2-HindIII [n = 21] or placebo [n = 11]) and were monitored for vaccine shedding, reactogenicity, RSV-antibody responses and RSV-associated medically attended acute respiratory illness (RSV-MAARI) and antibody responses during the following RSV season. RESULTS All 21 vaccinees were infected with vaccine; 20 (95%) shed vaccine (median peak titer, 3.5 log10 PFUs/mL with immunoplaque assay and 6.1 log10 copies/mL with polymerase chain reaction). Serum RSV-neutralizing antibodies and anti-RSV fusion immunoglobulin G increased ≥4-fold in 95% and 100% of vaccines, respectively. Mild upper respiratory tract symptoms and/or fever occurred in vaccinees (76%) and placebo recipients (18%). Over the RSV season, RSV-MAARI occurred in 2 vaccinees and 4 placebo recipients. Three vaccinees had ≥4-fold increases in serum RSV-neutralizing antibody titers after the RSV season without RSV-MAARI. CONCLUSIONS D46/NS2/N/ΔM2-2-HindIII had excellent infectivity and immunogenicity and primed vaccine recipients for anamnestic responses, encouraging further evaluation of this attenuation strategy. CLINICAL TRIALS REGISTRATION NCT03102034 and NCT03099291.
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live respiratory syncytial virus attenuated by M2 2 deletion and stabilized temperature sensitivity mutation 1030s is a promising vaccine candidate in children
The Journal of Infectious Diseases, 2020Co-Authors: Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Coleen K Cunningham, Charlotte Perlowski, Bhagvanji Thumar, Devasena Gnanashanmugam, Jennifer Libous, Jack Moye, Elizabeth SchappellAbstract:Background The safety and immunogenicity of live respiratory syncytial virus (RSV) candidate vaccine, LID/ΔM2-2/1030s, with deletion of RSV ribonucleic acid synthesis regulatory Protein M2-2 and genetically stabilized temperature-sensitivity mutation 1030s in the RSV polymerase Protein was evaluated in RSV-seronegative children. Methods Respiratory syncytial virus-seronegative children ages 6-24 months received 1 intranasal dose of 105 plaque-forming units (PFU) of LID/ΔM2-2/1030s (n = 21) or placebo (n = 11). The RSV serum antibodies, vaccine shedding, and reactogenicity were assessed. During the following RSV season, medically attended acute respiratory illness (MAARI) and pre- and postsurveillance serum antibody titers were monitored. Results Eighty-five percent of vaccinees shed LID/ΔM2-2/1030s vaccine (median peak nasal wash titers: 3.1 log10 PFU/mL by immunoplaque assay; 5.1 log10 copies/mL by reverse-transcription quantitative polymerase chain reaction) and had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms and fever were common (60% vaccinees and 27% placebo recipients). One vaccinee had grade 2 wheezing with rhinovirus but without concurrent LID/ΔM2-2/1030s shedding. Five of 19 vaccinees had ≥4-fold increases in antibody titers postsurveillance without RSV-MAARI, indicating anamnestic responses without significant illness after infection with community-acquired RSV. Conclusions LID/ΔM2-2/1030s had excellent infectivity without evidence of genetic instability, induced durable immunity, and primed for anamnestic antibody responses, making it an attractive candidate for further evaluation.
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live attenuated respiratory syncytial virus vaccine with deletion of rna synthesis regulatory Protein M2 2 and cold passage mutations is overattenuated
Open Forum Infectious Diseases, 2019Co-Authors: Coleen K Cunningham, Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Charlotte Perlowski, Bhagvanji Thumar, Devasena Gnanashanmugam, Jennifer Libous, Jack Moye, Elizabeth SchappellAbstract:Background The live respiratory syncytial virus (RSV) candidate vaccine LIDcpΔM2-2 is attenuated through deletion of M2-2 and 5 cold-passage mutations. Methods RSV-seronegative children aged 6-24 months received a single intranasal dose of 105 plaque-forming units (PFU) of LIDcpΔM2-2 or placebo. RSV serum antibodies, vaccine infectivity, and reactogenicity were assessed. Results Four of 11 (36%) vaccinees shed vaccine virus with median peak titers of 1.6 log10 PFU/mL by quantitative culture and 4.5 log10 copies/mL by polymerase chain reaction; 45% had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms or fever were common in vaccinees (64%) and placebo recipients (6/6, 100%). Conclusions RSV LIDcpΔM2-2 is overattenuated. Clinical Trial Numbers. NCT02890381, NCT02948127.
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live attenuated respiratory syncytial virus vaccine with deletion of rna synthesis regulatory Protein M2 2 and cold passage mutations is overattenuated
Open Forum Infectious Diseases, 2019Co-Authors: Coleen K Cunningham, Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Charlotte Perlowski, Bhagvanji Thumar, Devasena Gnanashanmugam, Jennifer Libous, Jack Moye, Elizabeth SchappellAbstract:Background The live respiratory syncytial virus (RSV) candidate vaccine LIDcpΔM2-2 is attenuated through deletion of M2-2 and 5 cold-passage mutations.
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live attenuated respiratory syncytial virus vaccine candidate with deletion of rna synthesis regulatory Protein M2 2 is highly immunogenic in children
The Journal of Infectious Diseases, 2018Co-Authors: Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Coleen K Cunningham, Megan Valentine, Charlotte Perlowski, Bhagvanji Thumar, Devasena Gnanashanmugam, George K Siberry, Elizabeth SchappellAbstract:Background Live respiratory syncytial virus (RSV) candidate vaccine LIDΔM2-2 is attenuated by deletion of the RSV RNA regulatory Protein M2-2, resulting in upregulated viral gene transcription and antigen expression but reduced RNA replication.
Coleen K Cunningham - One of the best experts on this subject based on the ideXlab platform.
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live attenuated respiratory syncytial virus vaccine with M2 2 deletion and with small hydrophobic noncoding region is highly immunogenic in children
The Journal of Infectious Diseases, 2020Co-Authors: Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Coleen K Cunningham, Charlotte Perlowski, Jennifer Libous, Jack Moye, Jennifer Oliva, Patrick Jeanphilippe, Elizabeth SchappellAbstract:BACKGROUND Respiratory syncytial virus (RSV) is the leading viral cause of severe pediatric respiratory illness, and vaccines are needed. Live RSV vaccine D46/NS2/N/ΔM2-2-HindIII, attenuated by deletion of the RSV RNA regulatory Protein M2-2, is based on previous candidate LID/ΔM2-2 but incorporates prominent differences from MEDI/ΔM2-2, which was more restricted in replication in phase 1. METHODS RSV-seronegative children aged 6-24 months received 1 intranasal dose (105 plaque-forming units [PFUs] of D46/NS2/N/ΔM2-2-HindIII [n = 21] or placebo [n = 11]) and were monitored for vaccine shedding, reactogenicity, RSV-antibody responses and RSV-associated medically attended acute respiratory illness (RSV-MAARI) and antibody responses during the following RSV season. RESULTS All 21 vaccinees were infected with vaccine; 20 (95%) shed vaccine (median peak titer, 3.5 log10 PFUs/mL with immunoplaque assay and 6.1 log10 copies/mL with polymerase chain reaction). Serum RSV-neutralizing antibodies and anti-RSV fusion immunoglobulin G increased ≥4-fold in 95% and 100% of vaccines, respectively. Mild upper respiratory tract symptoms and/or fever occurred in vaccinees (76%) and placebo recipients (18%). Over the RSV season, RSV-MAARI occurred in 2 vaccinees and 4 placebo recipients. Three vaccinees had ≥4-fold increases in serum RSV-neutralizing antibody titers after the RSV season without RSV-MAARI. CONCLUSIONS D46/NS2/N/ΔM2-2-HindIII had excellent infectivity and immunogenicity and primed vaccine recipients for anamnestic responses, encouraging further evaluation of this attenuation strategy. CLINICAL TRIALS REGISTRATION NCT03102034 and NCT03099291.
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live respiratory syncytial virus attenuated by M2 2 deletion and stabilized temperature sensitivity mutation 1030s is a promising vaccine candidate in children
The Journal of Infectious Diseases, 2020Co-Authors: Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Coleen K Cunningham, Charlotte Perlowski, Bhagvanji Thumar, Devasena Gnanashanmugam, Jennifer Libous, Jack Moye, Elizabeth SchappellAbstract:Background The safety and immunogenicity of live respiratory syncytial virus (RSV) candidate vaccine, LID/ΔM2-2/1030s, with deletion of RSV ribonucleic acid synthesis regulatory Protein M2-2 and genetically stabilized temperature-sensitivity mutation 1030s in the RSV polymerase Protein was evaluated in RSV-seronegative children. Methods Respiratory syncytial virus-seronegative children ages 6-24 months received 1 intranasal dose of 105 plaque-forming units (PFU) of LID/ΔM2-2/1030s (n = 21) or placebo (n = 11). The RSV serum antibodies, vaccine shedding, and reactogenicity were assessed. During the following RSV season, medically attended acute respiratory illness (MAARI) and pre- and postsurveillance serum antibody titers were monitored. Results Eighty-five percent of vaccinees shed LID/ΔM2-2/1030s vaccine (median peak nasal wash titers: 3.1 log10 PFU/mL by immunoplaque assay; 5.1 log10 copies/mL by reverse-transcription quantitative polymerase chain reaction) and had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms and fever were common (60% vaccinees and 27% placebo recipients). One vaccinee had grade 2 wheezing with rhinovirus but without concurrent LID/ΔM2-2/1030s shedding. Five of 19 vaccinees had ≥4-fold increases in antibody titers postsurveillance without RSV-MAARI, indicating anamnestic responses without significant illness after infection with community-acquired RSV. Conclusions LID/ΔM2-2/1030s had excellent infectivity without evidence of genetic instability, induced durable immunity, and primed for anamnestic antibody responses, making it an attractive candidate for further evaluation.
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live attenuated respiratory syncytial virus vaccine with deletion of rna synthesis regulatory Protein M2 2 and cold passage mutations is overattenuated
Open Forum Infectious Diseases, 2019Co-Authors: Coleen K Cunningham, Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Charlotte Perlowski, Bhagvanji Thumar, Devasena Gnanashanmugam, Jennifer Libous, Jack Moye, Elizabeth SchappellAbstract:Background The live respiratory syncytial virus (RSV) candidate vaccine LIDcpΔM2-2 is attenuated through deletion of M2-2 and 5 cold-passage mutations. Methods RSV-seronegative children aged 6-24 months received a single intranasal dose of 105 plaque-forming units (PFU) of LIDcpΔM2-2 or placebo. RSV serum antibodies, vaccine infectivity, and reactogenicity were assessed. Results Four of 11 (36%) vaccinees shed vaccine virus with median peak titers of 1.6 log10 PFU/mL by quantitative culture and 4.5 log10 copies/mL by polymerase chain reaction; 45% had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms or fever were common in vaccinees (64%) and placebo recipients (6/6, 100%). Conclusions RSV LIDcpΔM2-2 is overattenuated. Clinical Trial Numbers. NCT02890381, NCT02948127.
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live attenuated respiratory syncytial virus vaccine with deletion of rna synthesis regulatory Protein M2 2 and cold passage mutations is overattenuated
Open Forum Infectious Diseases, 2019Co-Authors: Coleen K Cunningham, Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Charlotte Perlowski, Bhagvanji Thumar, Devasena Gnanashanmugam, Jennifer Libous, Jack Moye, Elizabeth SchappellAbstract:Background The live respiratory syncytial virus (RSV) candidate vaccine LIDcpΔM2-2 is attenuated through deletion of M2-2 and 5 cold-passage mutations.
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live attenuated respiratory syncytial virus vaccine candidate with deletion of rna synthesis regulatory Protein M2 2 is highly immunogenic in children
The Journal of Infectious Diseases, 2018Co-Authors: Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Coleen K Cunningham, Megan Valentine, Charlotte Perlowski, Bhagvanji Thumar, Devasena Gnanashanmugam, George K Siberry, Elizabeth SchappellAbstract:Background Live respiratory syncytial virus (RSV) candidate vaccine LIDΔM2-2 is attenuated by deletion of the RSV RNA regulatory Protein M2-2, resulting in upregulated viral gene transcription and antigen expression but reduced RNA replication.
Charlotte Perlowski - One of the best experts on this subject based on the ideXlab platform.
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live attenuated respiratory syncytial virus vaccine with M2 2 deletion and with small hydrophobic noncoding region is highly immunogenic in children
The Journal of Infectious Diseases, 2020Co-Authors: Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Coleen K Cunningham, Charlotte Perlowski, Jennifer Libous, Jack Moye, Jennifer Oliva, Patrick Jeanphilippe, Elizabeth SchappellAbstract:BACKGROUND Respiratory syncytial virus (RSV) is the leading viral cause of severe pediatric respiratory illness, and vaccines are needed. Live RSV vaccine D46/NS2/N/ΔM2-2-HindIII, attenuated by deletion of the RSV RNA regulatory Protein M2-2, is based on previous candidate LID/ΔM2-2 but incorporates prominent differences from MEDI/ΔM2-2, which was more restricted in replication in phase 1. METHODS RSV-seronegative children aged 6-24 months received 1 intranasal dose (105 plaque-forming units [PFUs] of D46/NS2/N/ΔM2-2-HindIII [n = 21] or placebo [n = 11]) and were monitored for vaccine shedding, reactogenicity, RSV-antibody responses and RSV-associated medically attended acute respiratory illness (RSV-MAARI) and antibody responses during the following RSV season. RESULTS All 21 vaccinees were infected with vaccine; 20 (95%) shed vaccine (median peak titer, 3.5 log10 PFUs/mL with immunoplaque assay and 6.1 log10 copies/mL with polymerase chain reaction). Serum RSV-neutralizing antibodies and anti-RSV fusion immunoglobulin G increased ≥4-fold in 95% and 100% of vaccines, respectively. Mild upper respiratory tract symptoms and/or fever occurred in vaccinees (76%) and placebo recipients (18%). Over the RSV season, RSV-MAARI occurred in 2 vaccinees and 4 placebo recipients. Three vaccinees had ≥4-fold increases in serum RSV-neutralizing antibody titers after the RSV season without RSV-MAARI. CONCLUSIONS D46/NS2/N/ΔM2-2-HindIII had excellent infectivity and immunogenicity and primed vaccine recipients for anamnestic responses, encouraging further evaluation of this attenuation strategy. CLINICAL TRIALS REGISTRATION NCT03102034 and NCT03099291.
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live respiratory syncytial virus attenuated by M2 2 deletion and stabilized temperature sensitivity mutation 1030s is a promising vaccine candidate in children
The Journal of Infectious Diseases, 2020Co-Authors: Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Coleen K Cunningham, Charlotte Perlowski, Bhagvanji Thumar, Devasena Gnanashanmugam, Jennifer Libous, Jack Moye, Elizabeth SchappellAbstract:Background The safety and immunogenicity of live respiratory syncytial virus (RSV) candidate vaccine, LID/ΔM2-2/1030s, with deletion of RSV ribonucleic acid synthesis regulatory Protein M2-2 and genetically stabilized temperature-sensitivity mutation 1030s in the RSV polymerase Protein was evaluated in RSV-seronegative children. Methods Respiratory syncytial virus-seronegative children ages 6-24 months received 1 intranasal dose of 105 plaque-forming units (PFU) of LID/ΔM2-2/1030s (n = 21) or placebo (n = 11). The RSV serum antibodies, vaccine shedding, and reactogenicity were assessed. During the following RSV season, medically attended acute respiratory illness (MAARI) and pre- and postsurveillance serum antibody titers were monitored. Results Eighty-five percent of vaccinees shed LID/ΔM2-2/1030s vaccine (median peak nasal wash titers: 3.1 log10 PFU/mL by immunoplaque assay; 5.1 log10 copies/mL by reverse-transcription quantitative polymerase chain reaction) and had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms and fever were common (60% vaccinees and 27% placebo recipients). One vaccinee had grade 2 wheezing with rhinovirus but without concurrent LID/ΔM2-2/1030s shedding. Five of 19 vaccinees had ≥4-fold increases in antibody titers postsurveillance without RSV-MAARI, indicating anamnestic responses without significant illness after infection with community-acquired RSV. Conclusions LID/ΔM2-2/1030s had excellent infectivity without evidence of genetic instability, induced durable immunity, and primed for anamnestic antibody responses, making it an attractive candidate for further evaluation.
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live attenuated respiratory syncytial virus vaccine with deletion of rna synthesis regulatory Protein M2 2 and cold passage mutations is overattenuated
Open Forum Infectious Diseases, 2019Co-Authors: Coleen K Cunningham, Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Charlotte Perlowski, Bhagvanji Thumar, Devasena Gnanashanmugam, Jennifer Libous, Jack Moye, Elizabeth SchappellAbstract:Background The live respiratory syncytial virus (RSV) candidate vaccine LIDcpΔM2-2 is attenuated through deletion of M2-2 and 5 cold-passage mutations. Methods RSV-seronegative children aged 6-24 months received a single intranasal dose of 105 plaque-forming units (PFU) of LIDcpΔM2-2 or placebo. RSV serum antibodies, vaccine infectivity, and reactogenicity were assessed. Results Four of 11 (36%) vaccinees shed vaccine virus with median peak titers of 1.6 log10 PFU/mL by quantitative culture and 4.5 log10 copies/mL by polymerase chain reaction; 45% had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms or fever were common in vaccinees (64%) and placebo recipients (6/6, 100%). Conclusions RSV LIDcpΔM2-2 is overattenuated. Clinical Trial Numbers. NCT02890381, NCT02948127.
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live attenuated respiratory syncytial virus vaccine with deletion of rna synthesis regulatory Protein M2 2 and cold passage mutations is overattenuated
Open Forum Infectious Diseases, 2019Co-Authors: Coleen K Cunningham, Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Charlotte Perlowski, Bhagvanji Thumar, Devasena Gnanashanmugam, Jennifer Libous, Jack Moye, Elizabeth SchappellAbstract:Background The live respiratory syncytial virus (RSV) candidate vaccine LIDcpΔM2-2 is attenuated through deletion of M2-2 and 5 cold-passage mutations.
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live attenuated respiratory syncytial virus vaccine candidate with deletion of rna synthesis regulatory Protein M2 2 is highly immunogenic in children
The Journal of Infectious Diseases, 2018Co-Authors: Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Coleen K Cunningham, Megan Valentine, Charlotte Perlowski, Bhagvanji Thumar, Devasena Gnanashanmugam, George K Siberry, Elizabeth SchappellAbstract:Background Live respiratory syncytial virus (RSV) candidate vaccine LIDΔM2-2 is attenuated by deletion of the RSV RNA regulatory Protein M2-2, resulting in upregulated viral gene transcription and antigen expression but reduced RNA replication.
Petronella Muresan - One of the best experts on this subject based on the ideXlab platform.
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live attenuated respiratory syncytial virus vaccine with M2 2 deletion and with small hydrophobic noncoding region is highly immunogenic in children
The Journal of Infectious Diseases, 2020Co-Authors: Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Coleen K Cunningham, Charlotte Perlowski, Jennifer Libous, Jack Moye, Jennifer Oliva, Patrick Jeanphilippe, Elizabeth SchappellAbstract:BACKGROUND Respiratory syncytial virus (RSV) is the leading viral cause of severe pediatric respiratory illness, and vaccines are needed. Live RSV vaccine D46/NS2/N/ΔM2-2-HindIII, attenuated by deletion of the RSV RNA regulatory Protein M2-2, is based on previous candidate LID/ΔM2-2 but incorporates prominent differences from MEDI/ΔM2-2, which was more restricted in replication in phase 1. METHODS RSV-seronegative children aged 6-24 months received 1 intranasal dose (105 plaque-forming units [PFUs] of D46/NS2/N/ΔM2-2-HindIII [n = 21] or placebo [n = 11]) and were monitored for vaccine shedding, reactogenicity, RSV-antibody responses and RSV-associated medically attended acute respiratory illness (RSV-MAARI) and antibody responses during the following RSV season. RESULTS All 21 vaccinees were infected with vaccine; 20 (95%) shed vaccine (median peak titer, 3.5 log10 PFUs/mL with immunoplaque assay and 6.1 log10 copies/mL with polymerase chain reaction). Serum RSV-neutralizing antibodies and anti-RSV fusion immunoglobulin G increased ≥4-fold in 95% and 100% of vaccines, respectively. Mild upper respiratory tract symptoms and/or fever occurred in vaccinees (76%) and placebo recipients (18%). Over the RSV season, RSV-MAARI occurred in 2 vaccinees and 4 placebo recipients. Three vaccinees had ≥4-fold increases in serum RSV-neutralizing antibody titers after the RSV season without RSV-MAARI. CONCLUSIONS D46/NS2/N/ΔM2-2-HindIII had excellent infectivity and immunogenicity and primed vaccine recipients for anamnestic responses, encouraging further evaluation of this attenuation strategy. CLINICAL TRIALS REGISTRATION NCT03102034 and NCT03099291.
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live respiratory syncytial virus attenuated by M2 2 deletion and stabilized temperature sensitivity mutation 1030s is a promising vaccine candidate in children
The Journal of Infectious Diseases, 2020Co-Authors: Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Coleen K Cunningham, Charlotte Perlowski, Bhagvanji Thumar, Devasena Gnanashanmugam, Jennifer Libous, Jack Moye, Elizabeth SchappellAbstract:Background The safety and immunogenicity of live respiratory syncytial virus (RSV) candidate vaccine, LID/ΔM2-2/1030s, with deletion of RSV ribonucleic acid synthesis regulatory Protein M2-2 and genetically stabilized temperature-sensitivity mutation 1030s in the RSV polymerase Protein was evaluated in RSV-seronegative children. Methods Respiratory syncytial virus-seronegative children ages 6-24 months received 1 intranasal dose of 105 plaque-forming units (PFU) of LID/ΔM2-2/1030s (n = 21) or placebo (n = 11). The RSV serum antibodies, vaccine shedding, and reactogenicity were assessed. During the following RSV season, medically attended acute respiratory illness (MAARI) and pre- and postsurveillance serum antibody titers were monitored. Results Eighty-five percent of vaccinees shed LID/ΔM2-2/1030s vaccine (median peak nasal wash titers: 3.1 log10 PFU/mL by immunoplaque assay; 5.1 log10 copies/mL by reverse-transcription quantitative polymerase chain reaction) and had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms and fever were common (60% vaccinees and 27% placebo recipients). One vaccinee had grade 2 wheezing with rhinovirus but without concurrent LID/ΔM2-2/1030s shedding. Five of 19 vaccinees had ≥4-fold increases in antibody titers postsurveillance without RSV-MAARI, indicating anamnestic responses without significant illness after infection with community-acquired RSV. Conclusions LID/ΔM2-2/1030s had excellent infectivity without evidence of genetic instability, induced durable immunity, and primed for anamnestic antibody responses, making it an attractive candidate for further evaluation.
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live attenuated respiratory syncytial virus vaccine with deletion of rna synthesis regulatory Protein M2 2 and cold passage mutations is overattenuated
Open Forum Infectious Diseases, 2019Co-Authors: Coleen K Cunningham, Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Charlotte Perlowski, Bhagvanji Thumar, Devasena Gnanashanmugam, Jennifer Libous, Jack Moye, Elizabeth SchappellAbstract:Background The live respiratory syncytial virus (RSV) candidate vaccine LIDcpΔM2-2 is attenuated through deletion of M2-2 and 5 cold-passage mutations. Methods RSV-seronegative children aged 6-24 months received a single intranasal dose of 105 plaque-forming units (PFU) of LIDcpΔM2-2 or placebo. RSV serum antibodies, vaccine infectivity, and reactogenicity were assessed. Results Four of 11 (36%) vaccinees shed vaccine virus with median peak titers of 1.6 log10 PFU/mL by quantitative culture and 4.5 log10 copies/mL by polymerase chain reaction; 45% had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms or fever were common in vaccinees (64%) and placebo recipients (6/6, 100%). Conclusions RSV LIDcpΔM2-2 is overattenuated. Clinical Trial Numbers. NCT02890381, NCT02948127.
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live attenuated respiratory syncytial virus vaccine with deletion of rna synthesis regulatory Protein M2 2 and cold passage mutations is overattenuated
Open Forum Infectious Diseases, 2019Co-Authors: Coleen K Cunningham, Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Charlotte Perlowski, Bhagvanji Thumar, Devasena Gnanashanmugam, Jennifer Libous, Jack Moye, Elizabeth SchappellAbstract:Background The live respiratory syncytial virus (RSV) candidate vaccine LIDcpΔM2-2 is attenuated through deletion of M2-2 and 5 cold-passage mutations.
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live attenuated respiratory syncytial virus vaccine candidate with deletion of rna synthesis regulatory Protein M2 2 is highly immunogenic in children
The Journal of Infectious Diseases, 2018Co-Authors: Elizabeth J Mcfarland, Ruth A Karron, Petronella Muresan, Coleen K Cunningham, Megan Valentine, Charlotte Perlowski, Bhagvanji Thumar, Devasena Gnanashanmugam, George K Siberry, Elizabeth SchappellAbstract:Background Live respiratory syncytial virus (RSV) candidate vaccine LIDΔM2-2 is attenuated by deletion of the RSV RNA regulatory Protein M2-2, resulting in upregulated viral gene transcription and antigen expression but reduced RNA replication.
