SARS-CoV-2 receptor binding domain displayed on HBsAg virus–like particles elicits protective immunity in macaques

Dalvie, Neil C.; Tostanoski, Lisa H.; Rodriguez-Aponte, Sergio A.; Kaur, Kawaljit; Bajoria, Sakshi; Kumru, Ozan S.; Martinot, Amanda J.; Chandrashekar, Abishek; McMahan, Katherine; Mercado, Noe B.; Yu, Jingyou; Chang, Aiquan; Giffin, Victoria; Nampanya, Felix; Patel, Shivani; Bowman, Lesley A.H.; Naranjo, Christopher A; Yun, Dongsoo; Flinchbaugh, Zach; Pessaint, Laurent; Brown, Renita; Velasco, Jason; Teow, Elyse; Cook, Anthony; Andersen, Hanne; Lewis, Mark G.; Camp, Danielle L.; Silverman, Judith M.; Nagar, Gaurav; Rao, Harish; Lothe, Rakesh R; Chandrasekharan, Rahul; Rajurkar, Meghraj P; Shaligram, Umesh; Kleanthous, Harry; Joshi, Sangeeta B.; Volkin, David B.; Biswas, Sumi; Love, J. Christopher; Barouch, Dan H.

doi:10.1126/sciadv.abl6015

Cited by 29 publications

(33 citation statements)

References 48 publications

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“…For example, a SARS-CoV-2 RBD displayed on hepatitis B surface antigen (HBsAg)-virus-like particles (VLPs) induced neutralizing antibodies against SARS-CoV-2 B.1.1.7 and B.1.351 variants and protective efficacy in non-human primates, with reduced viral titers in bronchoalveolar lavage and nasal mucosa. 47 Similarly, a RBD displayed on Cucumber mosaic virus incorporated tetanus toxin (CuMV TT ) VLPs elicited neutralizing antibodies in mice against SARS-CoV-2 B.1.351, P.1, and B.1.617.2 variants. 48 In addition, a lumazine synthase VLP vaccine displaying SARS-CoV-2 RBD induced potent neutralizing antibodies against SARS-CoV-2 B.1.1.7, B.1.351, and P.1 variants, protecting immunized mice from SARS-CoV-2 challenge, with reduced clinical signs and pathological changes in the lung.…”

Section: Discussionmentioning

confidence: 99%

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RBD-mRNA vaccine induces broadly neutralizing antibodies against Omicron and multiple other variants and protects mice from SARS-CoV-2 challenge

Shi¹,

Zheng²,

Zhang³

et al. 2022

Translational Research

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Section: Discussionmentioning

confidence: 99%

“… 49 Overall, the neutralizing antibody titers induced by RBD vaccines are generally lower against these SARS-CoV-2 variants than against the prototypic virus strain. 29 , 47 , 48 , 49 …”

Section: Discussionmentioning

confidence: 99%

RBD-mRNA vaccine induces broadly neutralizing antibodies against Omicron and multiple other variants and protects mice from SARS-CoV-2 challenge

Shi¹,

Zheng²,

Zhang³

et al. 2022

Translational Research

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“…[ 71 , 72 , 73 , 74 , 75 ] Some nanoparticle designs for covid‐19 have already been validated at the clinical stage. [ 76 , 77 , 78 , 79 , 80 , 81 ] To improve the immunogenicity of Pre and S2, the two proteins were incorporated into double‐layered protein nanoparticles. The resulting nanoparticles significantly enhanced virus‐neutralizing titers and ADCC activity.…”

Section: Discussionmentioning

confidence: 99%

SARS‐CoV‐2 Spike Stem Protein Nanoparticles Elicited Broad ADCC and Robust Neutralization against Variants in Mice

Wang

Dong

et al. 2022

Small

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first detected in September 2020 in southeast England and has shown enhanced transmissibility and increased mortality compared with the original lineage. [4,5] Moreover, B.1.351 (Beta, β) and P.1 (Gamma, γ) variants were first identified in South Africa and Brazil, respectively, and partially circumvented postinfection or vaccination immunity. [6][7][8][9][10][11][12][13][14][15] Subsequently, the novel B.1.617.2 (Delta, δ) variant that emerged in India spread quickly across the globe, [16][17][18][19] as it displayed increased transmissibility beyond B.1.1.7 and enhanced vaccine evasion like B.1.351. [20][21][22][23][24][25][26] The most heavily mutated variant so far identified in Botswana and named as B.1.1.529 (Omicron, ο), is rapidly becoming the dominant SARS-CoV-2 virus circulating globally and joins the World Health Organization (WHO) list of variants of concern with Delta, Alpha, Beta, and Gamma. [27,28] Such variants with striking antibody evasion and rapid transmission even in fully vaccinated individuals present a critical threat to pandemic control and disease treatment. [29][30][31][32][33][34][35] The spike protein (S) is the preferred target antigen for vaccine development, based on its essential function and abundant neutralizing epitopes. [36] S is a class I virus fusion protein including S1 and S2 subunits connected by a furin-like cleavage site. [37,38] With the receptor-binding domain (RBD), S1 recognizes and anchors the angiotensin-converting enzyme 2 (ACE2) on the host cellular membrane during viral infection. The fusion peptide (FP) in the S2 subunit mediates the fusion of the viral membrane with the cell membrane. [39][40][41][42] Based on the RBD and FP functions, S is transformed from the metastable prefusion conformation to the stable postfusion conformation during the S-protein-mediated viral cell entry through structural rearrangement. [43] Due to its integral role in infection, current messenger RNA (mRNA) and nonreplicating viral vector vaccines have used the stabilized prefusion conformation of S protein (Pre) as the major antigen to induce potent humoral and cellular immune responses. [39,[44][45][46][47][48] However, S-based vaccines face challenges as mutations continue to emerge. Most mutations occur on the relatively variable S1 subunit, the main target of vaccineinduced neutralizing antibodies. For instance, the D614G mutation exhibits enhanced replication and transmission during viral spread and has supplanted the ancestral virus and appears Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global pandemic. The virus is rapidly evolving, characterized by the emergence of several major variants. Stable prefusion spike protein (Pre) is the immunogen in current vaccines but is limited in protecting against different variants. Here, the immune responses induced by the relatively conserved stem subunit (S2) of spike protein versus Pre are investigated. Pre generates the most robust neutralization responses against SARS-CoV-2 variants in vesicular stoma...

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“…RBD protein was cloned, expressed in Komgataella phaffi , and purified as previously described ( 45 , 72 , 73 ). RBD-SpyTag antigens were conjugated overnight onto the HBsAg-SpyCatcher VLP ( 74 , 75 ). Beta RBD used in vaccine formulations was engineered to include mutations L452K and F490W to increase manufacturability and scalability as previously described ( 13 ).…”

Section: Methodsmentioning

confidence: 99%

RBD-VLP Vaccines Adjuvanted with Alum or SWE Protect K18-hACE2 Mice against SARS-CoV-2 VOC Challenge

Wong

Russ

Miller

et al. 2022

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SARS-CoV-2 receptor binding domain displayed on HBsAg virus–like particles elicits protective immunity in macaques

Cited by 29 publications

References 48 publications

RBD-mRNA vaccine induces broadly neutralizing antibodies against Omicron and multiple other variants and protects mice from SARS-CoV-2 challenge

RBD-mRNA vaccine induces broadly neutralizing antibodies against Omicron and multiple other variants and protects mice from SARS-CoV-2 challenge

SARS‐CoV‐2 Spike Stem Protein Nanoparticles Elicited Broad ADCC and Robust Neutralization against Variants in Mice

RBD-VLP Vaccines Adjuvanted with Alum or SWE Protect K18-hACE2 Mice against SARS-CoV-2 VOC Challenge

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