A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates

Abstract

While the rapid development of COVID-19 vaccines has been a scientific triumph, the need remains for a globally available vaccine that provides longer-lasting immunity against present and future SARS-CoV-2 variants of concern (VOCs). Here, we describe DCFHP, a ferritin-based, protein-nanoparticle vaccine candidate that, when formulated with aluminum hydroxide as the sole adjuvant (DCFHP-alum), elicits potent and durable neutralizing antisera in non-human primates against known VOCs, including Omicron BQ.1, as well as against SARS-CoV-1. Following a booster ~one year after the initial immunization, DCFHP-alum elicits a robust anamnestic response. To enable global accessibility, we generated a cell line that can enable production of thousands of vaccine doses per liter of cell culture and show that DCFHP-alum maintains potency for at least 14 days at temperatures exceeding standard room temperature. DCFHP-alum has potential as a once-yearly booster vaccine, and as a primary vaccine for pediatric use including in infants.

Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen produced from two different cell lines

“…Protein subunit antigens generally require adjuvants to enhance immune responses [18,19], and Powell et al (2021) [14] previously reported that the 2P construct of spike-ferritin-C nanoparticle construct (S∆C-Fer), when formulated with Quil-A and MPLA as adjuvants (prime+boost), generated high levels of neutralizing antibody titers in mice [14]. The ability of DCFHP antigen formulated with aluminum-salt adjuvants, with and without CpG oligonucleotides, to generate similarly robust immune response in mice and NHPs was recently reported by [17]. Formulations adjuvanted solely with aluminum-salts (alum), however, are ideal for use in LMICs since they are inexpensive, easy to produce at large-scale, and their clinical use is supported by decades of safety and efficacy data in childhood, adolescent and adult vaccines [20].…”

“…Previous and ongoing work demonstrate the prefusion SARS-CoV-2 spike protein fused to H. pylori ferritin induce high levels of neutralizing antibodies in mice and non-human primates [14][15][16]. In this work, we examined an updated version of the spike-ferritin-nanoparticle construct termed Delta-C70-Ferritin-HexaPro or DCFHP, to which four additional stabilizing proline mutations were introduced to the previously described 2P construct both of which include a 70 amino acids C-terminal truncation [14,17]. This updated version of the nanoparticle-based vaccine candidate, when formulated with aluminum hydroxide as the sole adjuvant, elicited potent and durable neutralizing antisera in mice and NHPs SARS-CoV-2 Wuhan-1 and several variants of concern, as well as against SARS-CoV-1 [17].…”

Prospects for developing an Hepatitis C virus E1E2‐based nanoparticle vaccine

“…Comparing FDC retention of these two NPs and the E2p‐E2mc3‐v1 NP could yield useful information that directs future NP studies. Ferritin has been used successfully in this context in other systems, most notably for SARS‐CoV‐2 spike, 159–162 so it appears to be a matter of matching the antigen to its most appropriate NP platform. For HCV E1E2, this represents an experimental challenge waiting to be met.…”

Plants as Biofactories for Therapeutic Proteins and Antiviral Compounds to Combat COVID-19

“…Therefore, there is still a pressing need for globally available vaccines that can provide more lasting immunity against current and future coronavirus variants [ 94 ]. A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera against known variants of concern, including Omicron BQ.1 and the previous virus version SARS-CoV-1, was just reported [ 182 ]. This offers great potential for the rapid response of the emerging SARS-CoV-2 variants and provides versatility for the future development of vaccines against other emerging coronaviruses.…”