Breadth of SARS-CoV-2 neutralization and protection induced by a nanoparticle vaccine

Li, Dapeng; Martinez, David R.; Schäfer, Alexandra; Chen, Haiyan; Barr, Maggie; Sutherland, Laura L.; Lee, Esther; Parks, Robert; Mielke, Dieter; Edwards, W. Daniel; Newman, Amanda; Bock, Kevin W.; Minai, Mahnaz; Nagata, Bianca M.; Gagné, Matthew; Douek, Daniel C.; DeMarco, C. Todd; Denny, Thomas N.; Oguin, Thomas; Brown, April; Rountree, Wes; Wang, Yunfei; Mansouri, Katayoun; Edwards, Robert J.; Ferrari, Guido; Sempowski, Gregory D.; Eaton, Amanda; Tang, Juanjie; Cain, Derek W.; Santra, Sampa; Pardi, Norbert; Weissman, Drew; Tomai, Mark A.; Fox, Christopher B.; Moore, Ian N.; Andersen, Hanne; Lewis, Mark G.; Golding, Hana; Seder, Robert A.; Khurana, Surender; Baric, Ralph S.; Montefiori, David C.; Saunders, Kevin O.; Haynes, Barton F.

doi:10.1038/s41467-022-33985-4

Cited by 48 publications

(32 citation statements)

References 62 publications

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“…However, it should be noted that non-stabilized S glycoprotein vaccines have been shown to provide protection as well, albeit at lower efficacy. This is in line with the abovementioned immune dominance of the RBD, which is most likely sufficiently exposed in non-native conformations of S. Indeed, numerous vaccine candidates composed of only RBDs demonstrated the significant immunogenicity and generation of neutralizing antibodies [ 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 ]. Furthermore, since the RBD contains conserved epitopes that are recognized across most circulating clades, specifically targeting conserved epitopes within the RBD may generate SARS-CoV-2 vaccines with broader cross-variant neutralization and thus protective activity [ 141 , 142 ].…”

Section: Importance Of Glycoprotein Stabilization For Vaccine Develop...supporting

confidence: 72%

SARS-CoV-2 S Glycoprotein Stabilization Strategies

Pedenko

Sulbarán

Guilligay

et al. 2023

Viruses

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The SARS-CoV-2 pandemic has again shown that structural biology plays an important role in understanding biological mechanisms and exploiting structural data for therapeutic interventions. Notably, previous work on SARS-related glycoproteins has paved the way for the rapid structural determination of the SARS-CoV-2 S glycoprotein, which is the main target for neutralizing antibodies. Therefore, all vaccine approaches aimed to employ S as an immunogen to induce neutralizing antibodies. Like all enveloped virus glycoproteins, SARS-CoV-2 S native prefusion trimers are in a metastable conformation, which primes the glycoprotein for the entry process via membrane fusion. S-mediated entry is associated with major conformational changes in S, which can expose many off-target epitopes that deviate vaccination approaches from the major aim of inducing neutralizing antibodies, which mainly target the native prefusion trimer conformation. Here, we review the viral glycoprotein stabilization methods developed prior to SARS-CoV-2, and applied to SARS-CoV-2 S, in order to stabilize S in the prefusion conformation. The importance of structure-based approaches is highlighted by the benefits of employing stabilized S trimers versus non-stabilized S in vaccines with respect to their protective efficacy.

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Section: Importance Of Glycoprotein Stabilization For Vaccine Develop...supporting

confidence: 72%

SARS-CoV-2 S Glycoprotein Stabilization Strategies

Pedenko

Sulbarán

Guilligay

et al. 2023

Viruses

View full text Add to dashboard Cite

show abstract

“…Besides boosting doses with various vaccines originating from wild-type SARS-CoV-2 [ 32 , 33 ], vaccines composed of antigens from SARS-CoV-2 VOCs are being developed, and some have reached the clinical trial phase [ 34 ]. To elicit broader cross-reactive immunity covering most SARS-CoV-2 variants, a major issue is which viral variant should be chosen [ 35 ] and which immunization strategy is preferred [ 36 , 37 ].…”

Section: Introductionmentioning

confidence: 99%

A DNA Vaccine Encoding the Full-Length Spike Protein of Beta Variant (B.1.351) Elicited Broader Cross-Reactive Immune Responses against Other SARS-CoV-2 Variants

Zhao¹,

Zhang²,

Ding³

et al. 2023

Vaccines

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The SARS-CoV-2 pandemic remains an ongoing threat to global health with emerging variants, especially the Omicron variant and its sub-lineages. Although large-scale vaccination worldwide has delivered outstanding achievements for COVID-19 prevention, a declining effectiveness to a different extent in emerging SARS-CoV-2 variants was observed in the vaccinated population. Vaccines eliciting broader spectrum neutralizing antibodies and cellular immune responses are urgently needed and important. To achieve this goal, rational vaccine design, including antigen modeling, screening and combination, vaccine pipelines, and delivery, are keys to developing a next-generation COVID-19 vaccine. In this study, we designed several DNA constructs based on codon-optimized spike coding regions of several SARS-CoV-2 variants and analyzed their cross-reactive antibodies, including neutralizing antibodies, and cellular immune responses against several VOCs in C57BL/6 mice. The results revealed that different SARS-CoV-2 VOCs induced different cross-reactivity; pBeta, a DNA vaccine encoding the spike protein of the Beta variant, elicited broader cross-reactive neutralizing antibodies against other variants including the Omicron variants BA.1 and BA.4/5. This result demonstrates that the spike antigen from the Beta variant potentially serves as one of the antigens for multivalent vaccine design and development against variants of SARS-CoV-2.

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“…It is important to note that these variant-proof strategies do not necessarily include distinct variant sequences because it is argued that a given vaccine candidate based on the ancestral SARS-CoV-2 antigen could offer superior immune responses that would cover a broad array of viruses. Hence, the RBD-sortase A-conjugated ferritin nanoparticle nanoparticle vaccine candidate developed at Duke University and based on the ancestral SARS-CoV-2 strain aims to be variant-proof ( 40 ). Other strategies seek to cover incrementally broader CoV space.…”

Section: Discussionmentioning

confidence: 99%

“…Hence, the second objective is to create a variant-proof SARS-CoV-2 vaccine. Different approaches aim to yield a variant-proof vaccine: multivalent platforms or formulations with distinct variants (with or without the ancestral SARS-CoV-2 S), inserts designed to elicit cellular responses (such as N), or the ancestral SARS-CoV-2 S in a platform deemed to elicit broader and more potent immunity ( 39 , 40 ). It is important to note that these variant-proof strategies do not necessarily include distinct variant sequences because it is argued that a given vaccine candidate based on the ancestral SARS-CoV-2 antigen could offer superior immune responses that would cover a broad array of viruses.…”

Section: Discussionmentioning

confidence: 99%

Design of a pan-betacoronavirus vaccine candidate through a phylogenetically informed approach

2023

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Coronaviruses are a diverse family of viruses that crossed over into humans at least seven times, precipitating mild to catastrophic outcomes. The severe acute respiratory syndrome coronavirus 2 pandemic renewed efforts to identify strains with zoonotic potential and to develop pan-coronavirus vaccines. The analysis of 2181 coronavirus genomes (from 102 host species) confirmed the limited sequence conservation across genera (alpha-, beta-, delta-, and gammacoronavirus) and proteins. A phylogenetically informed pan-coronavirus vaccine was not feasible because of high genetic heterogeneity across genera. We focused on betacoronaviruses and identified nonhuman-infecting receptor binding domain (RBD) sequences that were more genetically similar to human coronaviruses than expected given their phylogenetic divergence. These human-like RBDs defined three phylogenetic clusters. A vaccine candidate based on a representative sequence for each cluster covers the diversity estimated to protect against existing and future human-infecting betacoronaviruses. Our findings emphasize the potential value of conceptualizing prophylaxis against zoonoses in terms of genetic, rather than species, diversity.

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Breadth of SARS-CoV-2 neutralization and protection induced by a nanoparticle vaccine

Cited by 48 publications

References 62 publications

SARS-CoV-2 S Glycoprotein Stabilization Strategies

SARS-CoV-2 S Glycoprotein Stabilization Strategies

A DNA Vaccine Encoding the Full-Length Spike Protein of Beta Variant (B.1.351) Elicited Broader Cross-Reactive Immune Responses against Other SARS-CoV-2 Variants

Design of a pan-betacoronavirus vaccine candidate through a phylogenetically informed approach

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