A Phase 1/2 Randomized Study to Evaluate the Safety, Tolerability, and Immunogenicity of Nucleoside-Modified Messenger RNA Influenza Vaccines in Healthy Adults
<b>Background/Objectives:</b> Circulating influenza strains antigenically differing from vaccine antigens increase disease burden by decreasing vaccine efficacy. Nucleoside-modified mRNA (modRNA) influenza vaccines may facilitate rapid production allowing later antigen selection and impr...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-04-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/13/4/383 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850180037351833600 |
|---|---|
| author | Angela Branche Mark J. Mulligan Alok Maniar Orlando Puente Islamiat Oladipupo Graham Crowther Agnieszka M. Zareba Zhuobiao Yi Ingrid Scully Emily Gomme Kenneth Koury Nicholas Kitchin Pirada Suphaphiphat Allen Annaliesa S. Anderson Alejandra Gurtman Kelly Lindert |
| author_facet | Angela Branche Mark J. Mulligan Alok Maniar Orlando Puente Islamiat Oladipupo Graham Crowther Agnieszka M. Zareba Zhuobiao Yi Ingrid Scully Emily Gomme Kenneth Koury Nicholas Kitchin Pirada Suphaphiphat Allen Annaliesa S. Anderson Alejandra Gurtman Kelly Lindert |
| author_sort | Angela Branche |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> Circulating influenza strains antigenically differing from vaccine antigens increase disease burden by decreasing vaccine efficacy. Nucleoside-modified mRNA (modRNA) influenza vaccines may facilitate rapid production allowing later antigen selection and improved antigenic similarity compared to circulating strains. We studied different influenza modRNA vaccine (IRV) formulations and dose levels. <b>Methods:</b> This phase 1/2 randomized study evaluated IRV safety/tolerability and immunogenicity in healthy 18- through 85-year-olds. Based on safety and immunogenicity for different IRV doses, schedules, and valencies versus the quadrivalent influenza vaccine (QIV; Fluzone High-Dose Quadrivalent, Sanofi Pasteur) in phase 1 (65–85-year-olds), quadrivalent IRV (qIRV) was further evaluated in 65- through 85-year-olds and 18- through 64-year-olds in phase 2, leading to phase 3 dose selection. <b>Results:</b> Phase 1 (65–85-year-olds) safety/tolerability and immunogenicity findings supported qIRV 30-µg and 60-µg phase 2 assessment (18–85-year-olds, N = 610). qIRV was well tolerated. Injection site pain was the most frequently reported local reaction. Reactogenicity event incidences ≤ 7 days postvaccination for qIRV were generally higher versus QIV, observed more frequently in 18- through 64-year-olds than 65- through 85-year-olds, and showed dose-related trends (60 μg > 30 μg). qIRV and QIV adverse event profiles in 65- through 85-year-olds were similar. There were higher postvaccination hemagglutination inhibition assay geometric mean titers and fold rises and seroconversion rates observed with qIRV versus QIV for A strains, with no consistent pattern for B strains. Cell-mediated immune responses to qIRV by Day 7 showed overall higher T-cell responses against all strains versus QIV. Antibody and cell-mediated immune responses showed comparable trends across qIRV doses in 18- through 85-year-olds; a dose-related pattern was observed in 65- through 85-year-olds (60 μg > 30 μg). <b>Conclusions:</b> Phase 3 investigations of qIRV 60 µg in older adults and qIRV 30 µg in younger adults are warranted (ClinicalTrials.gov Identifier: NCT05052697). |
| format | Article |
| id | doaj-art-3ad75e1a6cd54b5ba3a9770e441cab98 |
| institution | OA Journals |
| issn | 2076-393X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-3ad75e1a6cd54b5ba3a9770e441cab982025-08-20T02:18:20ZengMDPI AGVaccines2076-393X2025-04-0113438310.3390/vaccines13040383A Phase 1/2 Randomized Study to Evaluate the Safety, Tolerability, and Immunogenicity of Nucleoside-Modified Messenger RNA Influenza Vaccines in Healthy AdultsAngela Branche0Mark J. Mulligan1Alok Maniar2Orlando Puente3Islamiat Oladipupo4Graham Crowther5Agnieszka M. Zareba6Zhuobiao Yi7Ingrid Scully8Emily Gomme9Kenneth Koury10Nicholas Kitchin11Pirada Suphaphiphat Allen12Annaliesa S. Anderson13Alejandra Gurtman14Kelly Lindert15Department of Medicine, Division of Infectious Diseases, University of Rochester, Rochester, NY 14642, USANew York University (NYU) Vaccine Center, NYU Grossman School of Medicine, New York, NY 10016, USAVaccine Research and Development, Pfizer Inc., Pearl River, NY 10965, USAMiami Dade Medical Research Institute, Miami, FL 33176, USAVaccine Research and Development, Pfizer Inc., Pearl River, NY 10965, USAVaccine Research and Development, Pfizer Ltd., Hurley SL6 6RJ, UKVaccine Research and Development, Pfizer Inc., Collegeville, PA 19426, USAVaccine Research and Development, Pfizer Inc., Collegeville, PA 19426, USAVaccine Research and Development, Pfizer Inc., Pearl River, NY 10965, USAVaccine Research and Development, Pfizer Inc., Pearl River, NY 10965, USAVaccine Research and Development, Pfizer Inc., Pearl River, NY 10965, USAVaccine Research and Development, Pfizer Ltd., Hurley SL6 6RJ, UKVaccine Research and Development, Pfizer Inc., Pearl River, NY 10965, USAVaccine Research and Development, Pfizer Inc., Pearl River, NY 10965, USAVaccine Research and Development, Pfizer Inc., Pearl River, NY 10965, USAVaccine Research and Development, Pfizer Inc., Cambridge, MA 02139, USA<b>Background/Objectives:</b> Circulating influenza strains antigenically differing from vaccine antigens increase disease burden by decreasing vaccine efficacy. Nucleoside-modified mRNA (modRNA) influenza vaccines may facilitate rapid production allowing later antigen selection and improved antigenic similarity compared to circulating strains. We studied different influenza modRNA vaccine (IRV) formulations and dose levels. <b>Methods:</b> This phase 1/2 randomized study evaluated IRV safety/tolerability and immunogenicity in healthy 18- through 85-year-olds. Based on safety and immunogenicity for different IRV doses, schedules, and valencies versus the quadrivalent influenza vaccine (QIV; Fluzone High-Dose Quadrivalent, Sanofi Pasteur) in phase 1 (65–85-year-olds), quadrivalent IRV (qIRV) was further evaluated in 65- through 85-year-olds and 18- through 64-year-olds in phase 2, leading to phase 3 dose selection. <b>Results:</b> Phase 1 (65–85-year-olds) safety/tolerability and immunogenicity findings supported qIRV 30-µg and 60-µg phase 2 assessment (18–85-year-olds, N = 610). qIRV was well tolerated. Injection site pain was the most frequently reported local reaction. Reactogenicity event incidences ≤ 7 days postvaccination for qIRV were generally higher versus QIV, observed more frequently in 18- through 64-year-olds than 65- through 85-year-olds, and showed dose-related trends (60 μg > 30 μg). qIRV and QIV adverse event profiles in 65- through 85-year-olds were similar. There were higher postvaccination hemagglutination inhibition assay geometric mean titers and fold rises and seroconversion rates observed with qIRV versus QIV for A strains, with no consistent pattern for B strains. Cell-mediated immune responses to qIRV by Day 7 showed overall higher T-cell responses against all strains versus QIV. Antibody and cell-mediated immune responses showed comparable trends across qIRV doses in 18- through 85-year-olds; a dose-related pattern was observed in 65- through 85-year-olds (60 μg > 30 μg). <b>Conclusions:</b> Phase 3 investigations of qIRV 60 µg in older adults and qIRV 30 µg in younger adults are warranted (ClinicalTrials.gov Identifier: NCT05052697).https://www.mdpi.com/2076-393X/13/4/383influenzavaccinationmodRNAimmunogenicitysafetytolerability |
| spellingShingle | Angela Branche Mark J. Mulligan Alok Maniar Orlando Puente Islamiat Oladipupo Graham Crowther Agnieszka M. Zareba Zhuobiao Yi Ingrid Scully Emily Gomme Kenneth Koury Nicholas Kitchin Pirada Suphaphiphat Allen Annaliesa S. Anderson Alejandra Gurtman Kelly Lindert A Phase 1/2 Randomized Study to Evaluate the Safety, Tolerability, and Immunogenicity of Nucleoside-Modified Messenger RNA Influenza Vaccines in Healthy Adults Vaccines influenza vaccination modRNA immunogenicity safety tolerability |
| title | A Phase 1/2 Randomized Study to Evaluate the Safety, Tolerability, and Immunogenicity of Nucleoside-Modified Messenger RNA Influenza Vaccines in Healthy Adults |
| title_full | A Phase 1/2 Randomized Study to Evaluate the Safety, Tolerability, and Immunogenicity of Nucleoside-Modified Messenger RNA Influenza Vaccines in Healthy Adults |
| title_fullStr | A Phase 1/2 Randomized Study to Evaluate the Safety, Tolerability, and Immunogenicity of Nucleoside-Modified Messenger RNA Influenza Vaccines in Healthy Adults |
| title_full_unstemmed | A Phase 1/2 Randomized Study to Evaluate the Safety, Tolerability, and Immunogenicity of Nucleoside-Modified Messenger RNA Influenza Vaccines in Healthy Adults |
| title_short | A Phase 1/2 Randomized Study to Evaluate the Safety, Tolerability, and Immunogenicity of Nucleoside-Modified Messenger RNA Influenza Vaccines in Healthy Adults |
| title_sort | phase 1 2 randomized study to evaluate the safety tolerability and immunogenicity of nucleoside modified messenger rna influenza vaccines in healthy adults |
| topic | influenza vaccination modRNA immunogenicity safety tolerability |
| url | https://www.mdpi.com/2076-393X/13/4/383 |
| work_keys_str_mv | AT angelabranche aphase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT markjmulligan aphase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT alokmaniar aphase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT orlandopuente aphase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT islamiatoladipupo aphase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT grahamcrowther aphase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT agnieszkamzareba aphase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT zhuobiaoyi aphase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT ingridscully aphase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT emilygomme aphase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT kennethkoury aphase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT nicholaskitchin aphase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT piradasuphaphiphatallen aphase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT annaliesasanderson aphase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT alejandragurtman aphase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT kellylindert aphase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT angelabranche phase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT markjmulligan phase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT alokmaniar phase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT orlandopuente phase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT islamiatoladipupo phase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT grahamcrowther phase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT agnieszkamzareba phase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT zhuobiaoyi phase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT ingridscully phase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT emilygomme phase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT kennethkoury phase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT nicholaskitchin phase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT piradasuphaphiphatallen phase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT annaliesasanderson phase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT alejandragurtman phase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults AT kellylindert phase12randomizedstudytoevaluatethesafetytolerabilityandimmunogenicityofnucleosidemodifiedmessengerrnainfluenzavaccinesinhealthyadults |