Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection.
David S. Khoury,Deborah Cromer,Arnold Reynaldi,Timothy E. Schlub,Timothy E. Schlub,Adam K. Wheatley,Jennifer A Juno,Kanta Subbarao,Stephen J. Kent,Stephen J. Kent,Stephen J. Kent,James A. Triccas,Miles P. Davenport +12 more
TLDR
It is shown that neutralization level is highly predictive of immune protection, and an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic is provided.Abstract:
Predictive models of immune protection from COVID-19 are urgently needed to identify correlates of protection to assist in the future deployment of vaccines. To address this, we analyzed the relationship between in vitro neutralization levels and the observed protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using data from seven current vaccines and from convalescent cohorts. We estimated the neutralization level for 50% protection against detectable SARS-CoV-2 infection to be 20.2% of the mean convalescent level (95% confidence interval (CI) = 14.4–28.4%). The estimated neutralization level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level; 95% CI = 0.7–13%, P = 0.0004). Modeling of the decay of the neutralization titer over the first 250 d after immunization predicts that a significant loss in protection from SARS-CoV-2 infection will occur, although protection from severe disease should be largely retained. Neutralization titers against some SARS-CoV-2 variants of concern are reduced compared with the vaccine strain, and our model predicts the relationship between neutralization and efficacy against viral variants. Here, we show that neutralization level is highly predictive of immune protection, and provide an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic. Estimates of the levels of neutralizing antibodies necessary for protection against symptomatic SARS-CoV-2 or severe COVID-19 are a fraction of the mean level in convalescent serum and will be useful in guiding vaccine rollouts.read more
Citations
More filters
Journal ArticleDOI
Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination
Katharina Röltgen,Sandra C. A. Nielsen,Oscar Silva,Sheren F. Younes,M. Zaslavsky,Cristina Costales,Fan Yang,Oliver F. Wirz,Daniel Solis,Ramona A. Hoh,A. Wang,Prabhu S. Arunachalam,Deana Colburg,Shu-hua Zhao,Emily Haraguchi,Alexandra S. Lee,Mihir Shah,Monali Manohar,Iris Chang,Fei Gao,Vamsee Mallajosyula,Chunfeng Li,James Liu,Massa J. Shoura,Sayantani B. Sindher,Elizabeth Parsons,Naranjargal Dashdorj,Naranbaatar Dashdorj,R W Monroe,Geidy E. Serrano,Thomas G. Beach,R. Sharon Chinthrajah,Gregory W. Charville,James L. Wilbur,Jacob N. Wohlstadter,Mark M. Davis,Bali Pulendran,Megan L. Troxell,George Sigal,Yasodha Natkunam,Benjamin A. Pinsky,Kari C. Nadeau,Scott D. Boyd +42 more
TL;DR: In this paper , the authors investigated whether antibodies stimulated by mRNA vaccination (BNT162b2), including third-dose boosting, differ from those generated by infection or adenoviral (ChAdOx1-S and Gam-COVID-Vac) or inactivated viral (BBIBP-CorV) vaccines.
Journal Article
A framework for assessing immunological correlates of protection in vaccine trials. Commentary
Jerald C. Sadoff,Janet Wittes,Li Qin,Peter B. Gilbert,Lawrence Corey,M. Juliana McElrath,Steven G. Self +6 more
TL;DR: In this article, the authors proposed precise definitions of these different concepts of immune correlates, using the nomenclature "correlate of risk," "level 1 surrogate of protection," and "level 2 surrogate ofprotection."
Journal ArticleDOI
Increased memory B cell potency and breadth after a SARS-CoV-2 mRNA boost
Frauke Muecksch,Zhijun Wang,Alice Cho,Christian Gaebler,Tarek Ben Tanfous,Justin DaSilva,Eva Bednarski,Victor Ramos,Shuaizhou Zong,B J Johnson,Raphael Raspe,Dennis Schaefer-Babajew,Irina Shimeliovich,M. Daga,Kai-Hui Yao,Fabian Schmidt,Katrina G. Millard,Martina Turroja,Mila Jankovic,Thiago Y. Oliveira,Anna Gazumyan,Marina Caskey,Theodora Hatziioannou,Paul D. Bieniasz,Michel C. Nussenzweig +24 more
TL;DR: In this paper , the authors examined the memory B cell repertoire in a longitudinal cohort of individuals receiving three mRNA vaccine doses and found that the third dose is accompanied by an increase in, and evolution of, receptor-binding domain (RBD)-specific memory B cells.
Posted ContentDOI
The hyper-transmissible SARS-CoV-2 Omicron variant exhibits significant antigenic change, vaccine escape and a switch in cell entry mechanism
Brian J. Willett,Joe Grove,Oscar A. MacLean,Craig Wilkie,Nicola S Logan,Giuditta De Lorenzo,Wilhelm Furnon,Samuel Scott,M. Manali,Agnieszka M. Szemiel,Shirin Ashraf,Elen Vink,William T. Harvey,Chris Davis,Richard J. Orton,Joseph Hughes,P Holland,Vanessa K. A. Silva,David J Pascall,Kathryn Puxty,Ana da Silva Filipe,Gonzalo Yebra,Sharif Shaaban Muhammad Shaaban,Matthew T. G. Holden,Rute Maria Pinto,Rory Gunson,Kate Templeton,Pablo R. Murcia,Arvind H. Patel,John Haughney,David Robertson,Massimo Palmarini,Surajit Ray,E. Thomson +33 more
TL;DR: It is shown that immunity from natural infection (without vaccination) is more protective than two doses of vaccine but inferior to three doses, and fundamental changes in the Omicron entry process in vitro, towards TMPRSS2-independent fusion, representing a major shift in the replication properties of SARS-CoV-2.
Journal ArticleDOI
SARS-CoV-2 breakthrough infections elicit potent, broad, and durable neutralizing antibody responses
Alexandra C. Walls,Kaitlin R. Sprouse,John E. Bowen,Anshu Joshi,Nicholas Franko,Mary Jane Navarro,Cameron Stewart,Elisabetta Cameroni,Matthew McCallum,Erin A. Goecker,Emily J. Degli-Angeli,Jennifer Logue,Alexander L. Greninger,Davide Corti,Helen Y. Chu,David Veesler +15 more
TL;DR: In this paper , the authors demonstrate that breakthrough infections induce serum-binding and neutralizing antibody responses that are markedly more potent, durable, and resilient to spike mutations observed in variants than those in subjects who received only 2 doses of vaccine.
References
More filters
Journal ArticleDOI
Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine.
Fernando P. Polack,Stephen J. Thomas,Nicholas Kitchin,Judith Absalon,Alejandra Gurtman,Stephen Lockhart,John L. Perez,Gonzalo Pérez Marc,Edson D. Moreira,Cristiano Zerbini,Ruth Bailey,Kena A. Swanson,Satrajit Roychoudhury,Kenneth Koury,Ping Li,Warren Kalina,David A. Cooper,Robert W. Frenck,Laura L. Hammitt,Özlem Türeci,Haylene Nell,Axel Schaefer,Serhat Ünal,Dina B. Tresnan,Susan Mather,Philip R. Dormitzer,Ugur Sahin,Kathrin U. Jansen,William C. Gruber +28 more
TL;DR: A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older and safety over a median of 2 months was similar to that of other viral vaccines.
Journal ArticleDOI
Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.
Merryn Voysey,Clemens Sac.,Shabir A. Madhi,Lily Yin Weckx,P M Folegatti,Parvinder K. Aley,Brian Angus,Vicky L. Baillie,Shaun Barnabas,Q E Bhorat,S Bibi,Carmen Briner,P Cicconi,Andrea M. Collins,R Colin-Jones,Clare L. Cutland,Thomas C. Darton,Keertan Dheda,Duncan Cja.,Emary Krw.,Katie J. Ewer,Lee Fairlie,Saul N. Faust,Shuo Feng,Daniela M. Ferreira,Adam Finn,Anna Goodman,Catherine M. Green,Christopher A Green,Paul T. Heath,Christopher Hill,Helen Hill,Ian Hirsch,Hodgson Shc.,Allen Izu,S Jackson,D Jenkin,Joe Ccd.,S Kerridge,Anthonet Koen,Gaurav Kwatra,Rajeka Lazarus,Alison M. Lawrie,A Lelliott,Vincenzo Libri,Patrick J. Lillie,R Mallory,Mendes Ava.,Eveline Pipolo Milan,Angela M. Minassian,Alastair McGregor,Hazel Morrison,Y Mujadidi,Amit J Nana,P J O’Reilly,S D Padayachee,A Pittella,E Plested,Katrina M Pollock,M N Ramasamy,S Rhead,Alexandre Vargas Schwarzbold,Nisha Singh,Andrew Smith,R Song,Matthew D. Snape,Eduardo Sprinz,Rebecca K. Sutherland,R Tarrant,E. Thomson,M E Török,Mark Toshner,Turner Dpj.,Johan Vekemans,Tonya Villafana,Watson Mee.,C J Williams,Alexander D. Douglas,Hill Avs.,Teresa Lambe,Sarah C. Gilbert,Andrew J. Pollard +81 more
TL;DR: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials.
Journal ArticleDOI
Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine.
Lindsey R. Baden,Hana M. El Sahly,Brandon Essink,Karen L. Kotloff,Sharon E. Frey,Rick Novak,David Diemert,Stephen A. Spector,Nadine Rouphael,C. Buddy Creech,John W McGettigan,Shishir Khetan,Nathan Segall,Joel Solis,Adam Brosz,Carlos Fierro,Howard J. Schwartz,Kathleen M. Neuzil,Lawrence Corey,Peter B. Gilbert,Holly Janes,Dean Follmann,Mary A. Marovich,John R. Mascola,Laura Polakowski,Julie E. Ledgerwood,Barney S. Graham,Hamilton Bennett,Rolando Pajon,Conor Knightly,Brett Leav,Weiping Deng,Honghong Zhou,Shu Liang Han,Melanie Ivarsson,Jacqueline Miller,Tal Z Zaks +36 more
TL;DR: The mRNA-1273 vaccine as discussed by the authors is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.
Journal ArticleDOI
An mRNA Vaccine against SARS-CoV-2 — Preliminary Report
Lisa A. Jackson,Evan J. Anderson,Nadine Rouphael,Paul C. Roberts,Mamodikoe Makhene,Rhea N. Coler,Michele Paine McCullough,James D. Chappell,Mark R. Denison,Laura J. Stevens,Andrea J. Pruijssers,Adrian B. McDermott,Britta Flach,Nicole A. Doria-Rose,Kizzmekia S. Corbett,Kaitlyn M. Morabito,Sijy O’Dell,Stephen D. Schmidt,Phillip A. Swanson,Marcelino Padilla,John R. Mascola,Kathleen M. Neuzil,Hamilton Bennett,Wellington Sun,Etza Peters,Mat Makowski,Jim Albert,Kaitlyn Cross,Wendy Buchanan,Rhonda Pikaart-Tautges,Julie E. Ledgerwood,Barney S. Graham,John H. Beigel +32 more
TL;DR: The mRNA-1273 vaccine induced anti-SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified, which support further development of this vaccine.
Journal ArticleDOI
Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection.
Jennifer M. Dan,Jennifer M. Dan,Jose Mateus,Yu Kato,Kathryn M. Hastie,Esther Dawen Yu,Caterina E. Faliti,Alba Grifoni,Sydney I. Ramirez,Sydney I. Ramirez,Sonya Haupt,April Frazier,Catherine Nakao,Vamseedhar Rayaprolu,Stephen A. Rawlings,Bjoern Peters,Bjoern Peters,Florian Krammer,Viviana Simon,Erica Ollmann Saphire,Erica Ollmann Saphire,Davey M. Smith,Daniela Weiskopf,Alessandro Sette,Alessandro Sette,Shane Crotty,Shane Crotty +26 more
TL;DR: This article analyzed multiple compartments of circulating immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 254 samples from 188 COVID-19 cases, including 43 samples at ≥ 6 months after infection.
Related Papers (5)
Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine.
Fernando P. Polack,Stephen J. Thomas,Nicholas Kitchin,Judith Absalon,Alejandra Gurtman,Stephen Lockhart,John L. Perez,Gonzalo Pérez Marc,Edson D. Moreira,Cristiano Zerbini,Ruth Bailey,Kena A. Swanson,Satrajit Roychoudhury,Kenneth Koury,Ping Li,Warren Kalina,David A. Cooper,Robert W. Frenck,Laura L. Hammitt,Özlem Türeci,Haylene Nell,Axel Schaefer,Serhat Ünal,Dina B. Tresnan,Susan Mather,Philip R. Dormitzer,Ugur Sahin,Kathrin U. Jansen,William C. Gruber +28 more
Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine.
Lindsey R. Baden,Hana M. El Sahly,Brandon Essink,Karen L. Kotloff,Sharon E. Frey,Rick Novak,David Diemert,Stephen A. Spector,Nadine Rouphael,C. Buddy Creech,John W McGettigan,Shishir Khetan,Nathan Segall,Joel Solis,Adam Brosz,Carlos Fierro,Howard J. Schwartz,Kathleen M. Neuzil,Lawrence Corey,Peter B. Gilbert,Holly Janes,Dean Follmann,Mary A. Marovich,John R. Mascola,Laura Polakowski,Julie E. Ledgerwood,Barney S. Graham,Hamilton Bennett,Rolando Pajon,Conor Knightly,Brett Leav,Weiping Deng,Honghong Zhou,Shu Liang Han,Melanie Ivarsson,Jacqueline Miller,Tal Z Zaks +36 more
Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection.
Jennifer M. Dan,Jennifer M. Dan,Jose Mateus,Yu Kato,Kathryn M. Hastie,Esther Dawen Yu,Caterina E. Faliti,Alba Grifoni,Sydney I. Ramirez,Sydney I. Ramirez,Sonya Haupt,April Frazier,Catherine Nakao,Vamseedhar Rayaprolu,Stephen A. Rawlings,Bjoern Peters,Bjoern Peters,Florian Krammer,Viviana Simon,Erica Ollmann Saphire,Erica Ollmann Saphire,Davey M. Smith,Daniela Weiskopf,Alessandro Sette,Alessandro Sette,Shane Crotty,Shane Crotty +26 more
Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant.
Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.
Merryn Voysey,Clemens Sac.,Shabir A. Madhi,Lily Yin Weckx,P M Folegatti,Parvinder K. Aley,Brian Angus,Vicky L. Baillie,Shaun Barnabas,Q E Bhorat,S Bibi,Carmen Briner,P Cicconi,Andrea M. Collins,R Colin-Jones,Clare L. Cutland,Thomas C. Darton,Keertan Dheda,Duncan Cja.,Emary Krw.,Katie J. Ewer,Lee Fairlie,Saul N. Faust,Shuo Feng,Daniela M. Ferreira,Adam Finn,Anna Goodman,Catherine M. Green,Christopher A Green,Paul T. Heath,Christopher Hill,Helen Hill,Ian Hirsch,Hodgson Shc.,Allen Izu,S Jackson,D Jenkin,Joe Ccd.,S Kerridge,Anthonet Koen,Gaurav Kwatra,Rajeka Lazarus,Alison M. Lawrie,A Lelliott,Vincenzo Libri,Patrick J. Lillie,R Mallory,Mendes Ava.,Eveline Pipolo Milan,Angela M. Minassian,Alastair McGregor,Hazel Morrison,Y Mujadidi,Amit J Nana,P J O’Reilly,S D Padayachee,A Pittella,E Plested,Katrina M Pollock,M N Ramasamy,S Rhead,Alexandre Vargas Schwarzbold,Nisha Singh,Andrew Smith,R Song,Matthew D. Snape,Eduardo Sprinz,Rebecca K. Sutherland,R Tarrant,E. Thomson,M E Török,Mark Toshner,Turner Dpj.,Johan Vekemans,Tonya Villafana,Watson Mee.,C J Williams,Alexander D. Douglas,Hill Avs.,Teresa Lambe,Sarah C. Gilbert,Andrew J. Pollard +81 more