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Adjuvanting a subunit COVID-19 vaccine to induce protective immunity #MMPMID33873199
Arunachalam PS; Walls AC; Golden N; Atyeo C; Fischinger S; Li C; Aye P; Navarro MJ; Lai L; Edara VV; Roltgen K; Rogers K; Shirreff L; Ferrell DE; Wrenn S; Pettie D; Kraft JC; Miranda MC; Kepl E; Sydeman C; Brunette N; Murphy M; Fiala B; Carter L; White AG; Trisal M; Hsieh CL; Russell-Lodrigue K; Monjure C; Dufour J; Spencer S; Doyle-Meyers L; Bohm RP; Maness NJ; Roy C; Plante JA; Plante KS; Zhu A; Gorman MJ; Shin S; Shen X; Fontenot J; Gupta S; O'Hagan DT; Van Der Most R; Rappuoli R; Coffman RL; Novack D; McLellan JS; Subramaniam S; Montefiori D; Boyd SD; Flynn JL; Alter G; Villinger F; Kleanthous H; Rappaport J; Suthar MS; King NP; Veesler D; Pulendran B
Nature 2021[Jun]; 594 (7862): 253-258 PMID33873199show ga
The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative(1). 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 alpha-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).
Nature 2021 ; 594 (7862): 253-258
