A replicon RNA vaccine can induce durable protective immunity from SARS-CoV-2 in nonhuman primates after neutralizing antibodies have waned.
The global SARS-CoV-2 pandemic prompted rapid development of COVID-19 vaccines. Although several vaccines have received emergency approval through various public health agencies, the SARS-CoV-2 pandemic continues. Emergent variants of concern, waning immunity in the vaccinated, evidence that vaccine...
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Public Library of Science (PLoS)
2023-04-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011298&type=printable |
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| author | Megan A O'Connor David W Hawman Kimberly Meade-White Shanna Leventhal Wenjun Song Samantha Randall Jacob Archer Thomas B Lewis Brieann Brown Megan N Fredericks Kaitlin R Sprouse Hillary C Tunggal Mara Maughan Naoto Iwayama Chul Ahrens William Garrison Solomon Wangari Kathryn A Guerriero Patrick Hanley Jamie Lovaglio Greg Saturday David Veesler Paul T Edlefsen Amit P Khandhar Heinz Feldmann Deborah Heydenburg Fuller Jesse H Erasmus |
| author_facet | Megan A O'Connor David W Hawman Kimberly Meade-White Shanna Leventhal Wenjun Song Samantha Randall Jacob Archer Thomas B Lewis Brieann Brown Megan N Fredericks Kaitlin R Sprouse Hillary C Tunggal Mara Maughan Naoto Iwayama Chul Ahrens William Garrison Solomon Wangari Kathryn A Guerriero Patrick Hanley Jamie Lovaglio Greg Saturday David Veesler Paul T Edlefsen Amit P Khandhar Heinz Feldmann Deborah Heydenburg Fuller Jesse H Erasmus |
| author_sort | Megan A O'Connor |
| collection | DOAJ |
| description | The global SARS-CoV-2 pandemic prompted rapid development of COVID-19 vaccines. Although several vaccines have received emergency approval through various public health agencies, the SARS-CoV-2 pandemic continues. Emergent variants of concern, waning immunity in the vaccinated, evidence that vaccines may not prevent transmission and inequity in vaccine distribution have driven continued development of vaccines against SARS-CoV-2 to address these public health needs. In this report, we evaluated a novel self-amplifying replicon RNA vaccine against SARS-CoV-2 in a pigtail macaque model of COVID-19 disease. We found that this vaccine elicited strong binding and neutralizing antibody responses against homologous virus. We also observed broad binding antibody against heterologous contemporary and ancestral strains, but neutralizing antibody responses were primarily targeted to the vaccine-homologous strain. While binding antibody responses were sustained, neutralizing antibody waned to undetectable levels in some animals after six months but were rapidly recalled and conferred protection from disease when the animals were challenged 7 months after vaccination as evident by reduced viral replication and pathology in the lower respiratory tract, reduced viral shedding in the nasal cavity and lower concentrations of pro-inflammatory cytokines in the lung. Cumulatively, our data demonstrate in pigtail macaques that a self-amplifying replicon RNA vaccine can elicit durable and protective immunity to SARS-CoV-2 infection. Furthermore, these data provide evidence that this vaccine can provide durable protective efficacy and reduce viral shedding even after neutralizing antibody responses have waned to undetectable levels. |
| format | Article |
| id | doaj-art-d4af23eb43be40bcaa467db922cd5121 |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2023-04-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Pathogens |
| spelling | doaj-art-d4af23eb43be40bcaa467db922cd51212025-08-20T03:42:07ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-04-01194e101129810.1371/journal.ppat.1011298A replicon RNA vaccine can induce durable protective immunity from SARS-CoV-2 in nonhuman primates after neutralizing antibodies have waned.Megan A O'ConnorDavid W HawmanKimberly Meade-WhiteShanna LeventhalWenjun SongSamantha RandallJacob ArcherThomas B LewisBrieann BrownMegan N FredericksKaitlin R SprouseHillary C TunggalMara MaughanNaoto IwayamaChul AhrensWilliam GarrisonSolomon WangariKathryn A GuerrieroPatrick HanleyJamie LovaglioGreg SaturdayDavid VeeslerPaul T EdlefsenAmit P KhandharHeinz FeldmannDeborah Heydenburg FullerJesse H ErasmusThe global SARS-CoV-2 pandemic prompted rapid development of COVID-19 vaccines. Although several vaccines have received emergency approval through various public health agencies, the SARS-CoV-2 pandemic continues. Emergent variants of concern, waning immunity in the vaccinated, evidence that vaccines may not prevent transmission and inequity in vaccine distribution have driven continued development of vaccines against SARS-CoV-2 to address these public health needs. In this report, we evaluated a novel self-amplifying replicon RNA vaccine against SARS-CoV-2 in a pigtail macaque model of COVID-19 disease. We found that this vaccine elicited strong binding and neutralizing antibody responses against homologous virus. We also observed broad binding antibody against heterologous contemporary and ancestral strains, but neutralizing antibody responses were primarily targeted to the vaccine-homologous strain. While binding antibody responses were sustained, neutralizing antibody waned to undetectable levels in some animals after six months but were rapidly recalled and conferred protection from disease when the animals were challenged 7 months after vaccination as evident by reduced viral replication and pathology in the lower respiratory tract, reduced viral shedding in the nasal cavity and lower concentrations of pro-inflammatory cytokines in the lung. Cumulatively, our data demonstrate in pigtail macaques that a self-amplifying replicon RNA vaccine can elicit durable and protective immunity to SARS-CoV-2 infection. Furthermore, these data provide evidence that this vaccine can provide durable protective efficacy and reduce viral shedding even after neutralizing antibody responses have waned to undetectable levels.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011298&type=printable |
| spellingShingle | Megan A O'Connor David W Hawman Kimberly Meade-White Shanna Leventhal Wenjun Song Samantha Randall Jacob Archer Thomas B Lewis Brieann Brown Megan N Fredericks Kaitlin R Sprouse Hillary C Tunggal Mara Maughan Naoto Iwayama Chul Ahrens William Garrison Solomon Wangari Kathryn A Guerriero Patrick Hanley Jamie Lovaglio Greg Saturday David Veesler Paul T Edlefsen Amit P Khandhar Heinz Feldmann Deborah Heydenburg Fuller Jesse H Erasmus A replicon RNA vaccine can induce durable protective immunity from SARS-CoV-2 in nonhuman primates after neutralizing antibodies have waned. PLoS Pathogens |
| title | A replicon RNA vaccine can induce durable protective immunity from SARS-CoV-2 in nonhuman primates after neutralizing antibodies have waned. |
| title_full | A replicon RNA vaccine can induce durable protective immunity from SARS-CoV-2 in nonhuman primates after neutralizing antibodies have waned. |
| title_fullStr | A replicon RNA vaccine can induce durable protective immunity from SARS-CoV-2 in nonhuman primates after neutralizing antibodies have waned. |
| title_full_unstemmed | A replicon RNA vaccine can induce durable protective immunity from SARS-CoV-2 in nonhuman primates after neutralizing antibodies have waned. |
| title_short | A replicon RNA vaccine can induce durable protective immunity from SARS-CoV-2 in nonhuman primates after neutralizing antibodies have waned. |
| title_sort | replicon rna vaccine can induce durable protective immunity from sars cov 2 in nonhuman primates after neutralizing antibodies have waned |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011298&type=printable |
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