Cross-protective antibodies against common endemic respiratory viruses
Abstract Respiratory syncytial virus (RSV), human metapneumovirus (HMPV), and human parainfluenza virus types one (HPIV1) and three (HPIV3) can cause severe disease and death in immunocompromised patients, the elderly, and those with underlying lung disease. A protective monoclonal antibody exists f...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-36459-3 |
| _version_ | 1797349876481130496 |
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| author | Madelyn Cabán Justas V. Rodarte Madeleine Bibby Matthew D. Gray Justin J. Taylor Marie Pancera Jim Boonyaratanakornkit |
| author_facet | Madelyn Cabán Justas V. Rodarte Madeleine Bibby Matthew D. Gray Justin J. Taylor Marie Pancera Jim Boonyaratanakornkit |
| author_sort | Madelyn Cabán |
| collection | DOAJ |
| description | Abstract Respiratory syncytial virus (RSV), human metapneumovirus (HMPV), and human parainfluenza virus types one (HPIV1) and three (HPIV3) can cause severe disease and death in immunocompromised patients, the elderly, and those with underlying lung disease. A protective monoclonal antibody exists for RSV, but clinical use is limited to high-risk infant populations. Hence, therapeutic options for these viruses in vulnerable patient populations are currently limited. Here, we present the discovery, in vitro characterization, and in vivo efficacy testing of two cross-neutralizing monoclonal antibodies, one targeting both HPIV3 and HPIV1 and the other targeting both RSV and HMPV. The 3 × 1 antibody is capable of targeting multiple parainfluenza viruses; the MxR antibody shares features with other previously reported monoclonal antibodies that are capable of neutralizing both RSV and HMPV. We obtained structures using cryo-electron microscopy of these antibodies in complex with their antigens at 3.62 Å resolution for 3 × 1 bound to HPIV3 and at 2.24 Å for MxR bound to RSV, providing a structural basis for in vitro binding and neutralization. Together, a cocktail of 3 × 1 and MxR could have clinical utility in providing broad protection against four of the respiratory viruses that cause significant morbidity and mortality in at-risk individuals. |
| first_indexed | 2024-03-08T12:36:43Z |
| format | Article |
| id | doaj.art-aecd1fc02f0340dea67b159c63ebb60a |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-08T12:36:43Z |
| publishDate | 2023-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-aecd1fc02f0340dea67b159c63ebb60a2024-01-21T12:25:48ZengNature PortfolioNature Communications2041-17232023-02-0114111510.1038/s41467-023-36459-3Cross-protective antibodies against common endemic respiratory virusesMadelyn Cabán0Justas V. Rodarte1Madeleine Bibby2Matthew D. Gray3Justin J. Taylor4Marie Pancera5Jim Boonyaratanakornkit6Vaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterAbstract Respiratory syncytial virus (RSV), human metapneumovirus (HMPV), and human parainfluenza virus types one (HPIV1) and three (HPIV3) can cause severe disease and death in immunocompromised patients, the elderly, and those with underlying lung disease. A protective monoclonal antibody exists for RSV, but clinical use is limited to high-risk infant populations. Hence, therapeutic options for these viruses in vulnerable patient populations are currently limited. Here, we present the discovery, in vitro characterization, and in vivo efficacy testing of two cross-neutralizing monoclonal antibodies, one targeting both HPIV3 and HPIV1 and the other targeting both RSV and HMPV. The 3 × 1 antibody is capable of targeting multiple parainfluenza viruses; the MxR antibody shares features with other previously reported monoclonal antibodies that are capable of neutralizing both RSV and HMPV. We obtained structures using cryo-electron microscopy of these antibodies in complex with their antigens at 3.62 Å resolution for 3 × 1 bound to HPIV3 and at 2.24 Å for MxR bound to RSV, providing a structural basis for in vitro binding and neutralization. Together, a cocktail of 3 × 1 and MxR could have clinical utility in providing broad protection against four of the respiratory viruses that cause significant morbidity and mortality in at-risk individuals.https://doi.org/10.1038/s41467-023-36459-3 |
| spellingShingle | Madelyn Cabán Justas V. Rodarte Madeleine Bibby Matthew D. Gray Justin J. Taylor Marie Pancera Jim Boonyaratanakornkit Cross-protective antibodies against common endemic respiratory viruses Nature Communications |
| title | Cross-protective antibodies against common endemic respiratory viruses |
| title_full | Cross-protective antibodies against common endemic respiratory viruses |
| title_fullStr | Cross-protective antibodies against common endemic respiratory viruses |
| title_full_unstemmed | Cross-protective antibodies against common endemic respiratory viruses |
| title_short | Cross-protective antibodies against common endemic respiratory viruses |
| title_sort | cross protective antibodies against common endemic respiratory viruses |
| url | https://doi.org/10.1038/s41467-023-36459-3 |
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