Adjuvanting a subunit COVID-19 vaccine to induce protective immunity
ABCD PBi
Adjuvanting a subunit COVID-19 vaccine to induce protective immunity
Autor:
Arunachalam, Prabhu S
;
Walls, Alexandra C
;
Golden, Nadia
;
Atyeo, Caroline
;
Fischinger, Stephanie
;
Li, Chunfeng
;
Aye, Pyone
;
Navarro, Mary Jane
;
Lai, Lilin
;
Edara, Venkata Viswanadh
;
Röltgen, Katharina
;
Rogers, Kenneth
;
Shirreff, Lisa
;
Ferrell, Douglas E
;
Wrenn, Samuel
;
Pettie, Deleah
;
Kraft, John C
;
Miranda, Marcos C
;
Kepl, Elizabeth
;
Sydeman, Claire
;
Brunette, Natalie
;
Murphy, Michael
;
Fiala, Brooke
;
Carter, Lauren
;
White, Alexander G
;
Trisal, Meera
;
Hsieh, Ching-Lin
;
Russell-Lodrigue, Kasi
;
Monjure, Christopher
;
Dufour, Jason
;
Spencer, Skye
;
Doyle-Meyers, Lara
;
Bohm, Rudolph P
;
Maness, Nicholas J
;
Roy, Chad
;
Plante, Jessica A
;
Plante, Kenneth S
;
Zhu, Alex
;
Gorman, Matthew J
;
Shin, Sally
;
Shen, Xiaoying
;
Fontenot, Jane
;
Gupta, Shakti
;
O'Hagan, Derek T
;
Van Der Most, Robbert
;
Rappuoli, Rino
;
Coffman, Robert L
;
Novack, David
;
McLellan, Jason S
;
Subramaniam, Shankar
;
Montefiori, David
;
Boyd, Scott D
;
Flynn, JoAnne L
;
Alter, Galit
;
Villinger, Francois
;
Kleanthous, Harry
;
Rappaport, Jay
;
Suthar, Mehul S
;
King, Neil P
;
Veesler, David
;
Pulendran, Bali
Assuntos:
Adjuvants
;
Adjuvants, Immunologic
;
Agonists
;
Alum Compounds
;
Animals
;
Antibodies
;
Antibodies, Neutralizing - immunology
;
Antibodies, Viral - immunology
;
Antibody response
;
Antigens
;
Bronchus
;
CD4 antigen
;
CD4-Positive T-Lymphocytes - cytology
;
CD4-Positive T-Lymphocytes - immunology
;
Clinical trials
;
Clinical Trials, Phase I as Topic
;
Clinical Trials, Phase II as Topic
;
Coronaviruses
;
COVID-19
;
COVID-19 - immunology
;
COVID-19 - prevention & control
;
COVID-19 - virology
;
COVID-19 vaccines
;
COVID-19 Vaccines - immunology
;
Disease Models, Animal
;
Hepatitis
;
Immunity
;
Immunity, Cellular
;
Immunity, Humoral
;
Immunization
;
Immunogenicity
;
Infections
;
Lymphocytes
;
Lymphocytes T
;
Macaca mulatta - immunology
;
Male
;
Nanoparticles
;
Neutralization
;
Neutralizing
;
Oligodeoxyribonucleotides
;
Pandemics
;
Proteins
;
Public health
;
Receptors
;
Reduction
;
SARS-CoV-2 - immunology
;
Severe acute respiratory syndrome
;
Severe acute respiratory syndrome coronavirus 2
;
Spike Glycoprotein, Coronavirus - chemistry
;
Spike Glycoprotein, Coronavirus - immunology
;
Spike protein
;
Squalene
;
TLR7 protein
;
TLR9 protein
;
Tocopherol
;
Toll-like receptors
;
Vaccines
;
Vaccines, Subunit - immunology
;
Viral diseases
;
Viruses
;
Vitamin E
É parte de:
Nature (London), 2021-06, Vol.594 (7862), p.253-258
Notas:
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Descrição:
The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative . Here we demonstrate the capacity of a subunit vaccine, comprising the SARS-CoV-2 spike protein receptor-binding domain displayed on an I53-50 protein nanoparticle scaffold (hereafter designated RBD-NP), to stimulate robust and durable neutralizing-antibody responses and protection against SARS-CoV-2 in rhesus macaques. We evaluated five adjuvants including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an α-tocopherol-containing oil-in-water emulsion; AS37, a Toll-like receptor 7 (TLR7) agonist adsorbed to alum; CpG1018-alum, a TLR9 agonist formulated in alum; and alum. RBD-NP immunization with AS03, CpG1018-alum, AS37 or alum induced substantial neutralizing-antibody and CD4 T cell responses, and conferred protection against SARS-CoV-2 infection in the pharynges, nares and bronchoalveolar lavage. The neutralizing-antibody response to live virus was maintained up to 180 days after vaccination with RBD-NP in AS03 (RBD-NP-AS03), and correlated with protection from infection. RBD-NP immunization cross-neutralized the B.1.1.7 SARS-CoV-2 variant efficiently but showed a reduced response against the B.1.351 variant. RBD-NP-AS03 produced a 4.5-fold reduction in neutralization of B.1.351 whereas the group immunized with RBD-NP-AS37 produced a 16-fold reduction in neutralization of B.1.351, suggesting differences in the breadth of the neutralizing-antibody response induced by these adjuvants. Furthermore, RBD-NP-AS03 was as immunogenic as a prefusion-stabilized spike immunogen (HexaPro) with AS03 adjuvant. These data highlight the efficacy of the adjuvanted RBD-NP vaccine in promoting protective immunity against SARS-CoV-2 and have led to phase I/II clinical trials of this vaccine (NCT04742738 and NCT04750343).
Editor:
England: Nature Publishing Group
Idioma:
Inglês