Two-Component Spike Nanoparticle Vaccine Protects Macaques from SARS-CoV-2 Infection

Brouwer, Philip J.M.; Brinkkemper, Mitch; Maisonasse, Pauline; Dereuddre‐Bosquet, Nathalie; Grobben, Marloes; Claireaux, Mathieu; Gast, Marlon de; Marlin, Romain; Chesnais, Virginie; Diry, Ségolène; Allen, Joel D.; Watanabe, Yasunori; Giezen, Julia M.; Kerster, Gius; Turner, Hannah L.; Straten, Karlijn van der; Linden, Cynthia A. van der; Aldon, Yoann; Naninck, Thibaut; Bontjer, Ilja; Burger, Judith A.; Poniman, Meliawati; Mykytyn, Anna Z; Okba, Nisreen M.A.; Schermer, Edith E.; Breemen, Mariëlle J. van; Ravichandran, Rashmi; Caniels, Tom G.; Schooten, Jelle van; Kahlaoui, Nidhal; Contreras, Vanessa; Lemaître, Julien; Chapon, Catherine; Fang, Raphaël Ho Tsong; Villaudy, Julien; Sliepen, Kwinten; Velden, Yme U. van der; Haagmans, Bart L.; Bree, Godelieve J. de; Ginhoux, Eric; Ward, Andrew B.; Crispin, Max; King, Neil P.; Werf, Sylvie van der; Gils, Marit J. van; Grand, Roger Le; Sanders, Rogier W.

doi:10.2139/ssrn.3732360

Cited by 28 publications

(66 citation statements)

References 18 publications

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“…Multivalent display using virus-like particle (VLP) or nanoparticle (NP) is the common strategy for vaccine development, such as the VLP comprising an array of 360 copies of the L1 capsid protein for the licensed HPV vaccine [15], or the eOD-GT8 60mer HIV-1 vaccine currently in clinical trials [16]. Spike protein or RBD of SARS-CoV-2 conjugated on NP were shown to elicit potent neutralizing antibody responses [17,18]. The Novavax COVID-19 nanoparticle vaccine, NVX-CoV2373, induced protection for mice [19] and macaques [20] against viral challenge and showed 89.3% efficacy in a Phase Ⅲ clinical trial conducted in the UK, by using a two-dose regimen.…”

Section: Introductionmentioning

confidence: 99%

One dose of COVID-19 nanoparticle vaccine REVC-128 protects against SARS-CoV-2 challenge at two weeks post-immunization

Gu¹,

Torres

Li³

et al. 2021

Emerging Microbes & Infections

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A COVID-19 vaccine with capability to induce early protection is needed to efficiently eliminate viral spread. Here, we demonstrate the development of a nanoparticle vaccine candidate, REVC-128, in which multiple trimeric spike ectodomain with glycine (G) at position 614 were multimerized onto a nanoparticle. In-vitro characterization of this vaccine confirms its structural and antigenic integrity. In-vivo immunogenicity evaluation in mice indicates that a single dose of this vaccine induces potent serum neutralizing antibody titer at two weeks post immunization, which is significantly higher than titer induced by trimeric spike protein without nanoparticle presentation. The comparison of serum binding to spike subunits between animals immunized by spike with and without nanoparticle presentation indicates that nanoparticle prefers the display of spike RBD (Receptor-Binding Domain) over S2 subunit, likely resulting in a more neutralizing but less cross-reactive antibody response. Moreover, a Syrian golden hamster in-vivo model for SARS-CoV-2 virus challenge was implemented at two weeks post a single dose of REVC-128 immunization. The results showed that vaccination protects hamsters against SARS-CoV-2 virus challenge with evidence of steady body weight, suppressed viral loads and alleviation of tissue damage for protected animals, compared with ~10% weight loss, high viral loads and tissue damage in unprotected animals. Furthermore, the data showed that vaccine REVC-128 is thermostable at up to 37°C for at least 4 weeks. These findings, along with history of safety for protein vaccines, suggest that the REVC-128 is a safe, stable and efficacious singleshot vaccine candidate to induce the earliest protection against SARS-CoV-2 infection.

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Section: Introductionmentioning

confidence: 99%

One dose of COVID-19 nanoparticle vaccine REVC-128 protects against SARS-CoV-2 challenge at two weeks post-immunization

Gu¹,

Torres

Li³

et al. 2021

Emerging Microbes & Infections

Self Cite

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“…This resulted in neutralizing antibodies, which could prevent the production of infectious virus in the rabbits. The technique can also be used to couple on the same particle multiple RBDs from different but related viruses [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Zoonoses Anticipation and Preparedness Initiative, stakeholders conference, February 4 & 5, 2021

Beer

Amery²,

Bosch

et al. 2021

Biologicals

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“…Infection rates were reduced by 70% in people who had received two doses of the Moderna vaccine (asymptomatic and symptomatic cases), 22 and by 95% with the Pfizer/BioNTech vaccine (national surveillance data in Israel) 23 . Studies in other primates suggests that the peak level and duration of infectivity are reduced in animals vaccinated against but nonetheless infected with SARS‐CoV‐2 24 …”

Section: Discussionmentioning

confidence: 99%

Failures of quarantine systems for preventing COVID‐19 outbreaks in Australia and New Zealand

Grout

Katar

Ouakrim

et al. 2021

Medical Journal of Australia

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Objectives To identify COVID‐19 quarantine system failures in Australia and New Zealand. Design, setting, participants Observational epidemiological study of travellers in managed quarantine in Australia and New Zealand, to 15 June 2021. Main outcome measures Number of quarantine system failures, and failure with respect to numbers of travellers and SARS‐CoV‐2‐positive travellers. Results We identified 22 quarantine system failures in Australia and ten in New Zealand to 15 June 2021. One failure initiated a COVID‐19 outbreak that caused more than 800 deaths (the Victorian “second wave”); nine lockdowns were linked with quarantine system failures. The failure risk was estimated to be 5.0 failures per 100 000 travellers passing through quarantine and 6.1 (95% CI, 4.0–8.3) failures per 1000 SARS‐CoV‐2‐positive travellers. The risk per 1000 SARS‐CoV‐2‐positive travellers was higher in New Zealand than Australia (relative risk, 2.0; 95% CI, 1.0–4.2). Conclusions Quarantine system failures can be costly in terms of lives and economic impact, including lockdowns. Our findings indicate that infection control in quarantine systems in Australia and New Zealand should be improved, including vaccination of quarantine workers and incoming travellers, or that alternatives to hotel‐based quarantine should be developed.

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Two-Component Spike Nanoparticle Vaccine Protects Macaques from SARS-CoV-2 Infection

Cited by 28 publications

References 18 publications

One dose of COVID-19 nanoparticle vaccine REVC-128 protects against SARS-CoV-2 challenge at two weeks post-immunization

One dose of COVID-19 nanoparticle vaccine REVC-128 protects against SARS-CoV-2 challenge at two weeks post-immunization

Zoonoses Anticipation and Preparedness Initiative, stakeholders conference, February 4 & 5, 2021

Failures of quarantine systems for preventing COVID‐19 outbreaks in Australia and New Zealand

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