Improved Titers against Influenza Drift Variants with a Nanoparticle Vaccine

Shinde, Vivek; Fries, Louis; Wu, Yukun; Agrawal, Sapeckshita; Cho, Iksung; Thomas, D. Nigel; Spindler, Michelle; Lindner, Elizabeth; Hahn, Timothy; Plested, Joyce S.; Flyer, David C.; Massare, Michael J.; Zhou, Bin; Fix, Amy; Smith, Gale; Glenn, Gregory M.

doi:10.1056/nejmc1803554

Cited by 48 publications

(48 citation statements)

References 4 publications

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“…Here, we showed that a full-length, stabilized prefusion SARS-CoV-2 spike glycoprotein vaccine (NVX-CoV2373) adjuvanted by Matrix-M can induce high levels of functional immunity in mice and baboons, and protects mice expressing hACE2 receptors in a live SARS-CoV-2 challenge. The functional immunity induced by the nanoparticle vaccine and Matrix-M adjuvant is clearly dependent on both the adjuvant and antigen components and mirrors the human experience with in uenza hemagglutinin vaccine 21 and a naïve population with ebola recombinant protein nanoparticle vaccines 22 . Immunization with NVX-CoV2373 at low doses in mice and nonhuman primate induced anti-S antibodies, hACE2-receptor inhibiting antibodies, and SARS-CoV-2 neutralizing antibodies after one dose with signi cantly increased titers after a booster immunization.…”

Section: Discussionmentioning

confidence: 61%

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

Tian

Patel

Haupt

et al. 2020

Preprint

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The COVID-19 pandemic continues to spread throughout the world with an urgent need for a safe and protective vaccine to effectuate herd immunity to control the spread of SARS-CoV-2. Here, we report the development of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) produced from the full-length spike (S) protein, stabilized in the prefusion conformation. Purified NVX-CoV2373 S form 27.2 nm nanoparticles that are thermostable and bind with high affinity to the human angiotensin-converting enzyme 2 (hACE2) receptor. In mice and baboons, low-dose NVX-CoV2373 with saponin-based Matrix-M adjuvant elicits high titer anti-S IgG that is associated with blockade of hACE2 receptor binding, virus neutralization, and protection against SARS-CoV-2 challenge in mice with no evidence of vaccine-associated enhanced respiratory disease (VAERD). NVX-CoV2373 vaccine also elicits multifunctional CD4+ and CD8+ T cells, CD4+ T follicular helper T cells (Tfh), and the generation of antigen-specific germinal center (GC) B cells in the spleen. These results support the ongoing phase 1/2 clinical evaluation of the safety and immunogenicity of NVX-CoV2327 with Matrix-M (NCT04368988).

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Section: Discussionmentioning

confidence: 61%

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

Tian

Patel

Haupt

et al. 2020

Preprint

Self Cite

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“…The administration of this tNIV with a saponin adjuvant (Matrix-M) in ferrets induced higher levels of neutralizing antibodies against a panel of A (H3N2) strains than a commercial inactivated vaccine (trivalent Fluzone). A Phase I/II clinical trial showed similar results in patients, where tNIV induced significantly greater HAI responses compared to trivalent Fluzone against not only previous strains, but a forward-drifted A/Singapore variant [46]. Another candidate is a chimeric HA (cHA) vaccine born from a collaboration between Icahn School of Medicine at Mount Sinai and GSK/NIH.…”

Section: Recombinant Ha Vaccinesmentioning

confidence: 93%

Better influenza vaccines: an industry perspective

et al. 2020

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Vaccination is the most effective measure at preventing influenza virus infections. However, current seasonal influenza vaccines are only protective against closely matched circulating strains. Even with extensive monitoring and annual reformulation our efforts remain one step behind the rapidly evolving virus, often resulting in mismatches and low vaccine effectiveness. Fortunately, many next-generation influenza vaccines are currently in development, utilizing an array of innovative techniques to shorten production time and increase the breadth of protection. This review summarizes the production methods of current vaccines, recent advances that have been made in influenza vaccine research, and highlights potential challenges that are yet to be overcome. Special emphasis is put on the potential role of glycoengineering in influenza vaccine development, and the advantages of removing the glycan shield on influenza surface antigens to increase vaccine immunogenicity. The potential for future development of these novel influenza vaccine candidates is discussed from an industry perspective.

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“…Similarly, the group using Sf9 insect cell platform engineered a recombinant trivalent NP influenza vaccine (tNIV), which when intramuscularly administered with Matrix-M to ferrets induced high levels of broadly neutralizing antibodies against A (H1N1) strain, B strain and, especially, a panel of all historic (2000-2017) A/H3N2 strains [66]. In particular, in a clinical trial involving 330 adults, the 60-μg dose of tNIV/50 μg Matrix-M induced significantly greater HA inhibition antibody responses against a panel of wild-type A (H3N2) strains than did the inactivated trivalent vaccine Fluzone [67], showing that Matrix-M/tNIV may be an efficient strategy for developing the effective universal influenza vaccines with additional advantage in avoidance of the mismatching Ags as occurred in conventional procedures.…”

Section: Vads Constructed With Iscoms Formed By Self-assembly Of Sapomentioning

confidence: 96%

Vaccine Adjuvant Delivery Systems Constructed Using Biocompatible Nanoparticles Formed through Self-Assembly of Small Molecules

Liu¹,

Qu²,

Liu³

et al. 2018

Immunization - Vaccine Adjuvant Delivery System and Strategies

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Subunit vaccines are playing a critical role in controlling numerous diseases and attracting more and more research interests due to their numerous advantages over conventional whole microbe-based vaccines. However, subunit vaccines are weak immunogens and thus have limited capacity in eliciting the humoral and cellular immunity against pathogens. Recently, nanoparticles (NPs) formed with certain small molecules through self-assembly have been employed as an effective carrier for subunit vaccines to play roles of adjuvant, delivery and stabilization of antigens, thus engendering a vaccine adjuvant-delivery system (VADS), which shows promises to overcome the hurdles in developing subunit vaccines. In particular, the small molecule-self-assembled NPs as a VADS can not only deliver vaccine ingredients to immune cells but also influence the immunoresponse toward a Th1 (type 1 T helper cell) and Th2 balanced pathway to establish both humoral and cellular immunity. This chapter describes the innovative VADSs based on the small molecule-self-assembled NPs, such as metal NPs (mNPs), emulsions, liposomes, and ISCOMs, which are elaborately designed for the development of subunit vaccines.

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Improved Titers against Influenza Drift Variants with a Nanoparticle Vaccine

Cited by 48 publications

References 4 publications

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

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

Better influenza vaccines: an industry perspective

Vaccine Adjuvant Delivery Systems Constructed Using Biocompatible Nanoparticles Formed through Self-Assembly of Small Molecules

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