Durable protection against the SARS-CoV-2 Omicron variant is induced by an adjuvanted subunit vaccine

Abstract

Despite the remarkable efficacy of COVID-19 vaccines, waning immunity and the emergence of SARS-CoV-2 variants such as Omicron represents a global health challenge. Here, we present data from a study in nonhuman primates demonstrating durable protection against the Omicron BA.1 variant induced by a subunit SARS-CoV-2 vaccine comprising the receptor binding domain of the ancestral strain (RBD-Wu) on the I53-50 nanoparticle adjuvanted with AS03, which was recently authorized for use in individuals 18 years or older. Vaccination induced neutralizing antibody (nAb) titers that were maintained at high concentrations for at least 1 year after two doses, with a pseudovirus nAb geometric mean titer (GMT) of 1978 and a live virus nAb GMT of 1331 against the ancestral strain but not against the Omicron BA.1 variant. However, a booster dose at 6 to 12 months with RBD-Wu or RBD-β (RBD from the Beta variant) displayed on I53-50 elicited high neutralizing titers against the ancestral and Omicron variants. In addition, we observed persistent neutralization titers against a panel of sarbecoviruses, including SARS-CoV. Furthermore, there were substantial and persistent memory T and B cell responses reactive to Beta and Omicron variants. Vaccination resulted in protection against Omicron infection in the lung and suppression of viral burden in the nares at 6 weeks after the final booster immunization. Even at 6 months after vaccination, we observed protection in the lung and rapid control of virus in the nares. These results highlight the durable and cross-protective immunity elicited by the AS03-adjuvanted RBD-I53-50 nanoparticle vaccine.

Virus-like particle displaying SARS-CoV-2 receptor binding domain elicits neutralizing antibodies and is protective in a challenge model

“…Further, we observed improved potency in naïve animals by formulating IVX-411 with MF59, an oil-in-water emulsion. Such results have been externally replicated for I53-50-based SARS-CoV-2 vaccines in naïve human patients [38,[41][42][43]. Our results are immunogenically similar to those observed from other RBD-based, single-component, SARS-…”

“…Further, we observed improved potency in naïve animals by formulating IVX-411 with MF59, an oil-in-water emulsion. Such results have been externally replicated for I53-50-based SARS-CoV-2 vaccines in naïve human patients [38,41–43]. Our results are immunogenically similar to those observed from other RBD-based, single-component, SARS-CoV-2 VLP vaccines, which use nanoparticles such as ferritin [44,45], hepatitis B surface antigen [46], or mi3 (a variant of the I3-01 VLP) [47–50], as well as biochemical conjugation methods such as SpyCatcher and sortase [45,47].…”

Distinct sensitivities to SARS-CoV-2 variants in vaccinated humans and mice

“…We compared neutralizing antibody responses elicited following vaccination of BALB/c mice with three distinct AddaVax-adjuvanted protein subunit immunogens. Mice were immunized at weeks 0 and 3 with a clinical-stage, multivalent RBD-nanoparticle (RBD-NP) (Arunachalam et al, 2021;Walls et al, 2020aWalls et al, , 2021Arunachalam et al, 2022;Song et al, 2022), an S ''2P'' prefusion-stabilized S (Pallesen et al, 2017;Walls et al, 2020a), or a next-generation prefusion-stabilized HexaPro S (Hsieh et al, 2020;Walls et al, 2021). Sera were collected 2, 5, and 8 weeks post-prime, and serum neutralizing activity (expressed as the dilution inhibiting 50% of entry: ID 50 ) was evaluated using single-round vesicular stomatitis virus (VSV) Report ll pseudotyped with G614 S, Beta S (B.1.351: L18F, D80A, D215G, L242-L244 deletion, R246I, K417N, E484K, N501Y, D614G, A701V), or Gamma S (P.1: L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027, V1176F) in two distinct cell lines (VeroE6/TMPRSS2 [Lempp et al, 2021] and HEK293T/human ACE2 [Crawford et al, 2020]).…”

Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

“…Currently, there is uncertainty whether vaccines matching dominant circulating SARS-CoV-2 variants such as those used for seasonal influenza are needed, or if the repeated use of Wuhan-Hu-1–based vaccines will suffice. Recent work showed that boosting previously immunized macaques with Beta or Omicron mRNA S vaccines or with Beta RBD nanoparticle vaccines elicited comparably high titers of antibodies broadly neutralizing multiple variants relative to Wuhan-Hu-1–based vaccines ( 59 – 61 ). Furthermore, administration of Wuhan-Hu-1–based vaccine boosters in humans was shown to elicit appreciable titers of neutralizing antibodies and prevent severe disease associated with Omicron infections ( 11 , 19 , 62 – 65 ).…”