Lyophilized, thermostable Spike or RBD immunogenic liposomes induce protective immunity against SARS-CoV-2 in mice

Mabrouk, Moustafa T.; Chiem, Kevin; Rujas, Edurne; Huang, Wei‐Chiao; Jahagirdar, Dushyant; Quinn, Breandan; Nair, Meera Surendran; Nissly, Ruth H.; Cavener, Victoria S.; Boyle, Nina R.; Sornberger, Ty; Kuchipudi, Suresh V.; Ortega, Joaquı́n; Julien, Jean-Philippe; Martínez-Sobrido, Luis; Lovell, Jonathan F.

doi:10.1126/sciadv.abj1476

Cited by 33 publications

(29 citation statements)

References 39 publications

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“…Beyond antigen stabilization, vaccine formulation—both in terms of multivalent antigen display and adjuvant selection—is a major component of subunit vaccine design. Several display platforms exist and have been used for TBV antigen presentation, including genetic fusions and affinity linkages ( Brod et al., 2018 ; Chichester et al., 2018 ; Mabrouk et al., 2020 ; Scaria et al., 2020 , 2021 ; Jardine et al., 2013 ; Huang et al., 2018 , 2020 ; Mabrouk et al., 2021 ). An advantage of the CPQ platform used in the present study is its ability to easily incorporate antigenic designs along with adjuvants for rapid immunogenicity screening.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Vaccination with a structure-based stabilized version of malarial antigen Pfs48/45 elicits ultra-potent transmission-blocking antibody responses

McLeod

Mabrouk²,

Miura³

et al. 2022

Immunity

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Section: Discussionmentioning

confidence: 99%

“…To assess the stability of constructs of interest bound in particle form, a Ni-NTA competition assay was carried out as previously described ( Mabrouk et al., 2021 ). Ni-NTA magnetic beads (ThermoFisher Scientific, catalog no.…”

Section: Methodsmentioning

confidence: 99%

Vaccination with a structure-based stabilized version of malarial antigen Pfs48/45 elicits ultra-potent transmission-blocking antibody responses

McLeod

Mabrouk²,

Miura³

et al. 2022

Immunity

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“…Liposome-displayed S and RBD were lyophilized with a 7.5% sucrose cryoprotectant that was found effective in inhibiting liposomal aggregation upon reconstitution. [120] The Adv. Mater.…”

Section: Thermostabilitymentioning

confidence: 99%

Advanced Materials for SARS‐CoV‐2 Vaccines

et al. 2022

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development, since it mediates viral entry and induces neutralizing antibody responses, which are predictive of protection from symptomatic SARS-CoV-2 infection. [2,3] As waves of new viral variants emerge, other targets such as the membrane (M), envelope (E), or nucleocapsid (N) proteins may emerge as complementary vaccine antigens to help increase breadth of protection. [4] S forms a homotrimeric structure comprising two domains, S1 and S2, separated by a Furin cleavage site (FCS). [5,6] S1 contains the receptor binding domain (RBD) which binds to human angiotensin converting enzyme 2 (hACE2) on host cells. Subsequently, proteolytic cleavage by Furin and by Transmembrane protease serine 2 (TMPRSS2) at the FCS and just upstream of the fusion peptide, respectively, activates the S2 fusion machinery leading to viral entry. [7] S is a class I fusion glycoprotein that undergoes major structural rearrangements from prefusion to post-fusion conformation during viral fusion to host cell membranes. It was previously shown that prefusion-stabilized class I fusion protein antigens better preserve neutralization epitopes for viruses including respiratory syncytial virus (RSV) fusion (F) glycoprotein. [8] Similar to the Middle East respiratory syndrome coronavirus (MERS-CoV) S protein, [9] two proline substitutions (2P) at residues 986 and 987 at the C-terminal boundary of the first heptad repeat were found to stabilize SARS-CoV-2 S in its prefusion conformation. [10] These 2P stabilizing mutations have been widely adopted in many SARS-CoV-2 vaccines including the Moderna mRNA-1273 vaccine (Spikevax), the Pfizer/BioNTech BNT162b2 vaccine (Comirnaty), the Novavax NVX-CoV2373 vaccine (Nuvaxovid), and the Johnson and Johnson Ad26.CoV2.S vaccine (Janssen COVID-19 Vaccine). [11] In contrast, the AstraZeneca/Oxford ChAdOx1 nCoV-19/AZD1222 (Vaxzevria) antigen uses the wildtype SARS-CoV-2 S sequence and cells transduced with the adenovirusvectored vaccine produce intact trimeric S, albeit with some proteolytic S degradation. [12] To mitigate this, another common antigen enhancement strategy used by NVX-CoV2373 [13] and Ad26.CoV2.S [14] for example, is to insert mutations or deletions at the proteolytic-prone FCS to improve antigen stability and preserve immunogenicity.As shown in the schematic illustration in Figure 1B, COVID-19 vaccines have taken on a wide variety of formats. Table 1 lists some of the vaccine types that have reported peerreviewed phase 3 clinical trial results so far. [16] Various advanced materials have emerged as vaccines for the S subunit antigen The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), has killed untold millions worldwide and has hurtled vaccines into the spotlight as a go-to approach to mitigate it. Advances in virology, genomics, structural biology, and vaccine technologies have enabled a rapid and unprecedented rollout of COVID-19 vaccines, although much of the developing world remains unvaccinated. Several new vaccine platform...

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“…Live Virus Neutralization (VN) assays. We evaluated the ability of epitope scaffolds and spike protein antibodies to neutralize SARS-CoV-2 using live virus neutralization (VN) assays that we previously described [42][43][44][45] . Briefly, serum samples were diluted twofold in triplicate and incubated with 100 tissue culture infective dose 50 (TCID50) units of SARS-CoV-2 strain USA-WA1/2020 (NR-52281-BEI Resources, USA) at 5% CO2 at 36 ± 2 °C for 60 min.…”

Section: Elisa Based On Ed2-decorated Magnetic Nanoparticle (Mnps)mentioning

confidence: 99%

Adaptation-proof SARS-CoV-2 vaccine design

Vishweshwaraiah

Hnath

Rackley

et al. 2022

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surface spike glycoprotein - a major antibody target - is critical for virus entry via engagement of human angiotensin-converting enzyme 2 (ACE2) receptor. Despite successes with existing vaccines and therapies that primarily target the receptor binding domain (RBD) of the spike protein, the susceptibility of RBD to mutations provides escape routes for the SARS-CoV-2 from neutralizing antibodies. On the other hand, structural conservation in the spike protein can be targeted to reduce escape mutations and achieve broad protection. Here, we designed candidate stable immunogens that mimic surface features of selected conserved regions of spike protein through ‘epitope grafting,’ in which we present the target epitope topology on diverse heterologous scaffolds that can structurally accommodate the spike epitopes. Structural characterization of the epitope-scaffolds showed stark agreement with our computational models and target epitopes. The sera from mice immunized with engineered designs display epitope-scaffolds and spike binding activity. We also demonstrated the utility of the designed epitope-scaffolds in diagnostic applications. Taken all together, our study provides important methodology for targeting the conserved, non-RBD structural motifs of spike protein for SARS-CoV-2 epitope vaccine design and demonstrates the potential utility of ‘epitope grafting’ in rational vaccine design.

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Lyophilized, thermostable Spike or RBD immunogenic liposomes induce protective immunity against SARS-CoV-2 in mice

Abstract: SARS-CoV-2 antigens that are displayed on liposomes and lyophilized are thermostable and protect mice from lethal virus challenge.

Cited by 33 publications

References 39 publications

Vaccination with a structure-based stabilized version of malarial antigen Pfs48/45 elicits ultra-potent transmission-blocking antibody responses

Vaccination with a structure-based stabilized version of malarial antigen Pfs48/45 elicits ultra-potent transmission-blocking antibody responses

Advanced Materials for SARS‐CoV‐2 Vaccines

Adaptation-proof SARS-CoV-2 vaccine design

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