Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques.
Margherita Rosati,Mahesh Agarwal,Xintao Hu,Santhi Devasundaram,Dimitris Stellas,Bhabadeb Chowdhury,Jenifer Bear,Robert Burns,Duncan Donohue,Laurent Pessaint,Hanne Leth Andersen,Mark G. Lewis,Evangelos Terpos,Meletios A. Dimopoulos,Alexander Wlodawer,James I. Mullins,David Venzon,George N. Pavlakis,Barbara K. Felber +18 more
Reads0
Chats0
TLDR
In this article, the authors tested the immunogenicity and protective efficacy of DNA-based vaccine regimens expressing different prefusion-stabilized Wuhan-Hu-1 SARS-CoV-2 Spike antigens upon intramuscular injection followed by electroporation in rhesus macaques.Abstract:
The speed of development, versatility and efficacy of mRNA-based vaccines have been amply demonstrated in the case of SARS-CoV-2. DNA vaccines represent an important alternative since they induce both humoral and cellular immune responses in animal models and in human trials. We tested the immunogenicity and protective efficacy of DNA-based vaccine regimens expressing different prefusion-stabilized Wuhan-Hu-1 SARS-CoV-2 Spike antigens upon intramuscular injection followed by electroporation in rhesus macaques. Different Spike DNA vaccine regimens induced antibodies that potently neutralized SARS-CoV-2 in vitro and elicited robust T cell responses. The antibodies recognized and potently neutralized a panel of different Spike variants including Alpha, Delta, Epsilon, Eta and A.23.1, but to a lesser extent Beta and Gamma. The DNA-only vaccine regimens were compared to a regimen that included co-immunization of Spike DNA and protein in the same anatomical site, the latter of which showed significant higher antibody responses. All vaccine regimens led to control of SARS-CoV-2 intranasal/intratracheal challenge and absence of virus dissemination to the lower respiratory tract. Vaccine-induced binding and neutralizing antibody titers and antibody-dependent cellular phagocytosis inversely correlated with transient virus levels in the nasal mucosa. Importantly, the Spike DNA+Protein co-immunization regimen induced the highest binding and neutralizing antibodies and showed the strongest control against SARS-CoV-2 challenge in rhesus macaques.read more
Citations
More filters
Journal ArticleDOI
T cells in SARS-CoV-2 infection and vaccination
TL;DR: Development of vaccines that specifically target T cells is called for, to meet the needs of patient groups for whom cellular immunity is weaker, such as the elderly and the immunosuppressed.
Journal ArticleDOI
Sequential Analysis of Binding and Neutralizing Antibody in COVID-19 Convalescent Patients at 14 Months After SARS-CoV-2 Infection
TL;DR: It is shown that convalescent patients maintain functional antibody responses for more than one year after infection, suggesting a strong long-lasting response after symptomatic disease that may offer a prolonged protection against re-infection.
Journal ArticleDOI
Low Spike Antibody Levels and Impaired BA.4/5 Neutralization in Patients with Multiple Myeloma or Waldenstrom’s Macroglobulinemia after BNT162b2 Booster Vaccination
Margherita Rosati,Evangelos Terpos,Jenifer Bear,Robert Burns,Santhi Devasundaram,Ioannis Ntanasis-Stathopoulos,Maria Gavriatopoulou,Efstathios Kastritis,Meletios A. Dimopoulos,George N. Pavlakis,Barbara K. Felber +10 more
TL;DR: In this paper , the authors compared the response to BNT162b2 mRNA vaccinations of patients with multiple myeloma (MM, n = 60) or Waldenstrom's macroglobulinemia (WM), with healthy vaccine recipients (n = 37).
Journal ArticleDOI
Distinct neutralization profile of spike variants by antibodies induced upon SARS-CoV-2 infection or vaccination.
Margherita Rosati,Evangelos Terpos,Mahesh Agarwal,Vangelis Karalis,Jenifer Bear,Robert Burns,Xintao Hu,Demetrios Papademetriou,Ioannis Ntanasis-Stathopoulos,Ioannis P. Trougakos,Meletios-Athanasios Dimopoulos,George N. Pavlakis,Barbara K. Felber +12 more
Journal ArticleDOI
Reduced Antibodies and Innate Cytokine Changes in SARS-CoV-2 BNT162b2 mRNA Vaccinated Transplant Patients With Hematological Malignancies
Cristina Bergamaschi,Maria Pagoni,Margherita Rosati,Matthew Angel,Ifigeneia Tzannou,Margarita Vlachou,I Darmani,Amirah Ullah,Jenifer Bear,Santhi Devasundaram,Robert Burns,Ioannis Baltadakis,Stavros Gigantes,Meletios A. Dimopoulos,George N. Pavlakis,Evangelos Terpos,Barbara K. Felber +16 more
TL;DR: The patients showed heterogeneous adaptive and innate responses with lower humoral and reduced innate cytokine responses to vaccination compared to naïve vaccine recipients, which offer novel prognostic approaches for potentiating the effectiveness of COVID-19 vaccination in transplant patients with hematological malignancies.
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
Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation.
Daniel Wrapp,Nianshuang Wang,Kizzmekia S. Corbett,Jory A. Goldsmith,Ching-Lin Hsieh,Olubukola M. Abiona,Barney S. Graham,Jason S. McLellan +7 more
TL;DR: The authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor, and test several published SARS-CoV RBD-specific monoclonal antibodies found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs.
Journal ArticleDOI
Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein.
Alexandra C. Walls,Young-Jun Park,M. Alejandra Tortorici,M. Alejandra Tortorici,Abigail Wall,Andrew T. McGuire,Andrew T. McGuire,David Veesler +7 more
TL;DR: It is demonstrating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination, and it is shown that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of Sars- coV- 2 S and SARS S bind with similar affinities to human ACE2, correlating with the efficient spread of SATS among humans.
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
mRNA vaccines — a new era in vaccinology
TL;DR: A detailed overview of mRNA vaccines is provided and future directions and challenges in advancing this promising vaccine platform to widespread therapeutic use are considered.
Related Papers (5)
DNA vaccine candidate encoding SARS-CoV-2 spike proteins elicited potent humoral and Th1 cell-mediated immune responses in mice.
Eakachai Prompetchara,Chutitorn Ketloy,Kittipan Tharakhet,Papatsara Kaewpang,Supranee Buranapraditkun,Teerasit Techawiwattanaboon,Suwitra Sathean-Anan-Kun,Patrawadee Pitakpolrat,Supaporn Watcharaplueksadee,Supaporn Phumiamorn,Wassana Wijagkanalan,Kanitha Patarakul,Tanapat Palaga,Kiat Ruxrungtham +13 more
Vaccination with SARS-CoV-2 Spike Protein and AS03 Adjuvant Induces Rapid Anamnestic Antibodies in the Lung and Protects Against Virus Challenge in Nonhuman Primates
Joseph R. Francica,Barbara J. Flynn,Kathryn E. Foulds,Amy T. Noe,Anne P. Werner,Ian N. Morre,Matthew Gagne,Timothy S. Johnston,Courtney Tucker,Rachel L. Davis,Britta Flach,Shayne F. Andrew,Evan Lamb,Dillon R. Flebbe,Saule T. Nurmukhambetova,Mitzi M. Donaldson,John-Paul Todd,Alex Lee Zhu,Alex Lee Zhu,Caroline Atyeo,Caroline Atyeo,Stephanie Fischinger,Stephanie Fischinger,Matthew J. Gorman,Sally Shin,Venkata Viswanadh Edara,Venkata Viswanadh Edara,Katharine Floyd,Katharine Floyd,Lilin Lai,Lilin Lai,Alida Tylor,Elizabeth McCarthy,Timothy Tibbitts,Hanne Leth Andersen,Anthony L. Cook,Alan Dodson,Laurent Pessaint,Alex Van Ry,Marguerite Koutsoukos,Cindy Gutzeit,I-Ting Teng,Tongqing Zhou,Dapeng Li,Barton F. Haynes,Peter D. Kwong,Adrian B. McDermott,Mark G. Lewis,Tong-Ming Fu,Roman Chicz,Robbert van der Most,Kizzmekia S. Corbett,Mehul S. Suthar,Mehul S. Suthar,Galit Alter,Nancy J. Sullivan,Daniel C. Douek,Barney S. Graham,Danilo Casimiro,Robert A. Seder +59 more
Low-dose Ad26.COV2.S protection against SARS-CoV-2 challenge in rhesus macaques.
Xuan He,Abishek Chandrashekar,Roland Zahn,Frank Wegmann,Jingyou Yu,Noe B. Mercado,Katherine McMahan,Amanda J. Martinot,Cesar Piedra-Mora,Sidney Beecy,Sarah Ducat,Ronnie Chamanza,Sietske K. Rosendahl Huber,Marjolein van Heerden,Leslie van der Fits,Erica N. Borducchi,Michelle A. Lifton,Jinyan Liu,Felix Nampanya,Shivani A. Patel,Lauren Peter,Lisa H. Tostanoski,Laurent Pessaint,Alex Van Ry,Brad Finneyfrock,Jason Velasco,Elyse Teow,Renita Brown,Anthony L. Cook,Hanne Leth Andersen,Mark G. Lewis,Hanneke Schuitemaker,Dan H. Barouch,Dan H. Barouch +33 more
Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques.
Hannah A.D. King,Hannah A.D. King,M. Gordon Joyce,M. Gordon Joyce,Ines Lakhal-Naouar,Ines Lakhal-Naouar,Aslaa Ahmed,Camila Macedo Cincotta,Camila Macedo Cincotta,Caroline Subra,Caroline Subra,Kristina K. Peachman,Holly R. Hack,Holly R. Hack,Rita E. Chen,Paul V. Thomas,Paul V. Thomas,Wei-Hung Chen,Wei-Hung Chen,Rajeshwer S. Sankhala,Rajeshwer S. Sankhala,Agnes Hajduczki,Agnes Hajduczki,Elizabeth J. Martinez,Elizabeth J. Martinez,Caroline E. Peterson,Caroline E. Peterson,William C. Chang,William C. Chang,Misook Choe,Misook Choe,Clayton A. Smith,Jarrett A. Headley,Jarrett A. Headley,Hanne A. Elyard,Anthony L. Cook,Alexander R. A. Anderson,Alexander R. A. Anderson,Kathryn McGuckin Wuertz,Ming Dong,Ming Dong,Isabella Swafford,Isabella Swafford,James Brett Case,Jeffrey R. Currier,Kerri G. Lal,Kerri G. Lal,Mihret F. Amare,Mihret F. Amare,Vincent Dussupt,Vincent Dussupt,Sebastian Molnar,Sebastian Molnar,Sharon P. Daye,Xiankun Zeng,Erica K. Barkei,Kendra J. Alfson,Hilary M. Staples,Ricardo Carrion,Shelly J. Krebs,Shelly J. Krebs,Dominic Paquin-Proulx,Dominic Paquin-Proulx,Nicos Karasavvas,Nicos Karasavvas,Victoria R. Polonis,Linda L. Jagodzinski,Sandhya Vasan,Sandhya Vasan,Paul T. Scott,Yaoxing Huang,Manoj S. Nair,David D. Ho,Natalia de Val,Michael S. Diamond,Mark G. Lewis,Mangala Rao,Gary R. Matyas,Gregory D. Gromowski,Sheila A. Peel,Nelson L. Michael,Kayvon Modjarrad,Diane L. Bolton,Diane L. Bolton +83 more
An intranasal vaccine durably protects against SARS-CoV-2 variants in mice.
Ahmed O. Hassan,Swathi Shrihari,Matthew J. Gorman,Baoling Ying,Dansu Yaun,Saravanan Raju,Rita E. Chen,Igor P. Dmitriev,Elena A. Kashentseva,Lucas J. Adams,Colin Mann,Meredith E. Davis-Gardner,Mehul S. Suthar,Pei Yong Shi,Erica Ollmann Saphire,Daved H. Fremont,David T. Curiel,Galit Alter,Michael S. Diamond +18 more