A Gamma-adapted recombinant subunit vaccine induces broadly neutralizing antibodies against SARS-CoV-2 variants and protects mice from infection

Abstract

The COVID-19 pandemic continues with the emergence of successive new variants of concern (VOC). One strategy to prevent breakthrough infections is developing safe and effective broad-spectrum vaccines. Here, we present preclinical studies of a RBD recombinant vaccine candidate derived from the Gamma SARS-CoV-2 variant adjuvanted with alum. Gamma RBD-derived antigen elicited better neutralizing antibody and T cell responses than formulation containing ancestral RBD antigen. The Gamma-adapted subunit vaccine elicited a long-lasting antibody response with cross-neutralizing activity against different VOC including the Omicron variant. Additionally, Gamma variant RBD-adapted vaccine elicited robust T cells responses with induction of Th1 and CD8+ T cell responses in spleen and lung. Vaccine-induced immunity protected K18-hACE2 mice from intranasal challenge with SARS-CoV-2 increasing survival, reducing body weight loss and viral burden in the lungs and brain. Importantly, the subunit vaccine demonstrated a potent effect as heterologous booster of different vaccine platforms including the non-replicating adenovirus vaccine ChAdOx1-S, the mRNA vaccine BNT162b2 and the inactivated SARS-CoV-2 vaccine BBIBP-CorV, increasing cross-reactive antibody responses. Our study indicates that the adjuvanted Gamma RBD vaccine is highly immunogenic and a broad-spectrum vaccine candidate to combat SARS-CoV-2 variants including Omicron.

Safety, tolerability, and immunogenicity of a new SARS-CoV-2 recombinant Gamma variant RBD-based protein adjuvanted vaccine, used as heterologous booster in healthy adults: a Phase 1 interim report

“…Similarly, booster shots with Beta variant-based vaccines elicit broad nAb responses against the Ancestral, the Beta and the Omicron BA.1 VOC, which were higher in terms of nAb GMT or GMFR than that elicited by the Ancestral prototype vaccines, or a homologous booster with BNT16b2. 10,20,21 Results presented in this work suggest that a booster with ARVAC-CG increases the breath of the nAb and are in agreement with non-clinical results of this vaccine formulation 13 .…”

“…Non-clinical studies of this vaccine prototype in mice indicated that the Gamma-variant vaccine-candidate is more immunogenic and induces a broader nAb response than the Ancestral vaccine-candidate. 13 In this interim report safety and immunogenicity data after a booster dose of ARVAC-CG vaccine from an ongoing first in human phase 1 study are presented.…”

“…Non-clinical studies of this vaccine prototype in mice indicated that the Gamma-variant vaccine-candidate is more immunogenic and induces a broader nAb response than the Ancestral vaccine-candidate. 13…”

Immunogenicity and Safety of Gamma, Omicron BA.4/5 and Bivalent SARS-CoV-2 RBD-based Protein Booster Vaccines in Adults Previously Immunized with Different Vaccine Platforms: a Phase II/III, Randomized, Clinical Trial

“…14 Moreover, the results from this trial support previous studies indicating increased immunogenicity and breadth of a Gamma-variant vaccine compared to the ancestralvariant vaccine. 13,14 To our knowledge, few trials have simultaneously assessed and compared the immunogenicity outcomes of several vaccine variants, as showed in this Phase III trial, comparing three vaccine versions. 18,19 Bivalent Ancestral/Omicron, Alpha/Beta, and Ancestral/Beta recombinant boosters have previously shown robust nAb responses in individuals who had received primary schemes based mostly on mRNA or Adenoviruses, [18][19][20] but a bivalent recombinant booster vaccine lacking the Ancestral/Alpha variants remained unassessed.…”

“…Preclinical studies demonstrated that the Gamma RBD version is more immunogenic than the ancestral RBD at inducing broader neutralizing antibodies (nAbs) even against distant variants, such as the Omicron BA.5. 13 In a Phase I trial, the vaccine was safe and elicited a robust and broad nAb response against several SARS-CoV-2 variants. 14 In this work, we present the results of a Phase II/III trial.…”