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
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• 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