SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice

Tian, Jing-Hui; Patel, Nita; Haupt, Robert; Zhou, Haixia; Weston, Stuart; Hammond, Holly; Lague, James; Portnoff, Alyse D.; Norton, James A.; Guebre‐Xabier, Mimi; Zhou, Bin; Jacobson, Kelsey; Maciejewski, Sonia; Khatoon, Rafia; Wiśniewska, Małgorzata; Moffitt, Will; Kluepfel-Stahl, Stefanie; Ekechukwu, Betty; Papin, James F.; Boddapati, Sarathi; Wong, C. Jason; Piedra, Pedro A.; Frieman, Matthew B.; Massare, Michael J.; Fries, Louis; Bengtsson, Karin; Stertman, Linda; Ellingsworth, Larry; Glenn, Gregory M.; Smith, Gale

doi:10.1101/2020.06.29.178509

Cited by 88 publications

(130 citation statements)

References 26 publications

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“…are made in baculovirus, the insect cell produce protein with man-9 glycosylation that may be sufficient for immune response induction, but may not recapitulate the antigenicity of virus grown in mammalian cells [5,[18][19]. Animal challenge studies will be conducted at a future date to examine the safety and efficacy of our candidate vaccine.…”

Section: Although the Leading Subunit Protein Covid-19 Vaccines By Dementioning

confidence: 99%

Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19

Kuo

Lin²,

Coffman

et al. 2020

Preprint

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The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 is a worldwide health emergency. The immense damage done to public health and economies has prompted a global race for cures and vaccines. In developing a COVID-19 vaccine, we applied technology previously used for MERS-CoV to produce a prefusion-stabilized SARS-CoV-2 spike protein by adding two proline substitutions at the top of the central helix (S-2P). To enhance immunogenicity and mitigate the potential vaccine-induced immunopathology, CpG 1018, a Th1-biasing synthetic toll-like receptor 9 (TLR9) agonist was selected as an adjuvant candidate. S-2P was combined with various adjuvants, including CpG 1018, and administered to mice to test its effectiveness in eliciting anti-SARS-CoV-2 neutralizing antibodies. S-2P in combination with CpG 1018 and aluminum hydroxide (alum) was found to be the most potent immunogen and induced high titer of spike-specific antibodies in sera of immunized mice. The neutralizing abilities were measured with pseudotyped lentivirus reporter or live wild-type SARS-CoV-2 with reciprocal inhibiting dilution (ID50) titers of 5120 and 2560, respectively. In addition, the antibodies elicited were also able to neutralize pseudovirus containing the spike protein of the recent dominating variant D614G. A marked Th-1 dominant response was noted from cytokines secreted by splenocytes of mice immunized with CpG 1018 and alum. No vaccine-related serious adverse effects were found in the dose-ranging study in rats administered single- or two-dose regimens. These data support continued development of CHO-derived S-2P formulated with CpG 1018/alum as a broadly protective candidate vaccine to prevent COVID-19 disease.

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Section: Although the Leading Subunit Protein Covid-19 Vaccines By Dementioning

confidence: 99%

Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19

Kuo

Lin²,

Coffman

et al. 2020

Preprint

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show abstract

“…Multiple studies employing a variety of vaccine formulations and modalities have now demonstrated that SARS-CoV-2 viral neutralization titers in small animals including mice and guinea pigs are predictive of immunogenicity in macaques and humans ( Figure 5E) [17][18][19][20]22,23,[33][34][35][36][37][40][41][42][43]45 . Despite promising immunogenicity in several cases, all of the above liquid formulations were either refrigerated or frozen prior to use.…”

Section: Discussionmentioning

confidence: 99%

“…Pichia expressed RBD was as immunogenic as the mRBD in terms of self-titers (Supplementary Figure 3A, 3B) but sera reacted poorly with mRBD and Spike-2P. Several studies have now shown that ACE2 competition titers and neutralizing antibody titers are highly correlated 22,31 . Hence serum competition assays were carried out ( Figure 5C).…”

Section: Addavax™ Adjuvanted Rbd Elicits Neutralizing Antibodies In Gmentioning

confidence: 92%

“…The spike ectodomain and full length spike formulations are important SARS-CoV-2 vaccine candidates 5,6,22 and it is therefore important to compare mRBD with these. We purified the Spike-2P stabilized ectodomain protein from Expi293F cells by single step nickel chelate affinity chromatography followed by tag removal with a purified yield of ~25 mg/L culture 5 .…”

Section: Design Of a Recombinant Rbd Subunit Vaccinementioning

confidence: 99%

“…Over 150 vaccine candidates are under development globally 16 . Some vaccine candidates that have entered rapidly into clinical phase testing include mRNA vaccine candidates by Moderna (mRNA-1273), BioNTech (BNT162b1) 17 , and CureVac (CVnCoV), a Chimpanzee Adenovirus vector vaccine by University of Oxford and AstraZeneca (ChAdOx1-S) 18 , a non-replicating adenovirus type-5 (Ad5) vaccine by Cansino (Ad5-nCoV) 19 , a DNA vaccine by Inovio (INO-4800) 20 , inactivated virus vaccines by Sinovac (PiCoVacc) 21 and Bharat Biotech (COVAXIN), a native like trimeric subunit spike protein vaccine by Clover Biopharmaceuticals /GSK/Dynavax (SCB-2019), and a full length recombinant glycoprotein nanoparticle vaccine by Novavax (NVX-CoV2373) 16,22 .…”

Section: Introductionmentioning

confidence: 99%

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Design of a highly thermotolerant, immunogenic SARS-CoV-2 spike fragment immunogen

Malladi

Singh

Pandey

et al. 2020

Preprint

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Virtually all SARS-CoV-2 vaccines currently in clinical testing are stored in a refrigerated or frozen state prior to use. This is a major impediment to deployment in resource-poor settings. Several use viral vectors or mRNA. In contrast to protein subunit vaccines, there is limited manufacturing expertise for these novel, nucleic acid based modalities, especially in the developing world. Neutralizing antibodies, the clearest known correlate of protection against SARS-CoV-2, are primarily directed against the Receptor Binding Domain (RBD) of the viral spike protein. We describe a monomeric, glycan engineered RBD protein fragment that is expressed at a purified yield of 200mg/L in unoptimized, mammalian cell culture and in contrast to a stabilized spike ectodomain, is tolerant of exposure to temperatures as high as 100°C when lyophilized, and upto 70°C in solution. In prime:boost guinea pig immunizations, when formulated with the MF59 like adjuvant AddaVax™, the RBD derivative elicited neutralizing antibodies with an endpoint geometric mean titer of ~415 against replicative virus, comparing favourably with several vaccine formulations currently in the clinic. These features of high yield, extreme thermotolerance and satisfactory immunogenicity suggest that such RBD subunit vaccine formulations hold great promise to combat COVID-19.

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Lipid‐Polymer Hybrid “Particle‐in‐Particle” Nanostructure Gene Delivery Platform Explored for Lyophilizable DNA and mRNA COVID‐19 Vaccines

Zhang

et al. 2022

Adv Funct Materials

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SARS‐CoV‐2 has led to a worldwide pandemic, catastrophically impacting public health and the global economy. Herein, a new class of lipid‐modified polymer poly (β‐amino esters) (L‐PBAEs) is developed via enzyme‐catalyzed esterification and further formulation of the L‐PBAEs with poly( d , l ‐lactide‐coglycolide)‐ b ‐poly(ethylene glycol) (PLGA‐PEG) leads to self‐assembly into a “particle‐in‐particle” (PNP) nanostructure for gene delivery. Out of 24 PNP candidates, the top‐performing PNP/C12‐PBAE nanoparticles efficiently deliver both DNA and mRNA in vitro and in vivo, presenting enhanced transfection efficacy, sustained gene release behavior, and excellent stability for at least 12 months of storage at −20 °C after lyophilization without loss of transfection efficacy. Encapsulated with spike encoded plasmid DNA and mRNA, the lipid‐modified polymeric PNP COVID‐19 vaccines successfully elicit spike‐specific antibodies and Th1‐biased T cell immune responses in immunized mice even after 12 months of lyophilized storage at −20 °C. This newly developed lipid‐polymer hybrid PNP nanoparticle system demonstrates a new strategy for both plasmid DNA and mRNA delivery with the capability of long‐term lyophilized storage.

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SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice

Cited by 88 publications

References 26 publications

Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19

Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19

Design of a highly thermotolerant, immunogenic SARS-CoV-2 spike fragment immunogen

Lipid‐Polymer Hybrid “Particle‐in‐Particle” Nanostructure Gene Delivery Platform Explored for Lyophilizable DNA and mRNA COVID‐19 Vaccines

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