Immunogenicity and safety in pigs of PHH-1V, a SARS-CoV-2 RBD fusion heterodimer vaccine candidate

Abstract

The continuing high global incidence of COVID-19 and the undervaccinated status of billions of persons strongly motivate the development of a new generation of efficacious vaccines. We have developed an adjuvanted vaccine candidate, PHH-1V, based on a protein comprising the receptor binding domain (RBD) of the Beta variant of SARS-CoV-2 fused in tandem with the equivalent domain of the Alpha variant, with its immunogenicity, safety and efficacy previously demonstrated in mouse models. In the present study, we immunized pigs with different doses of PHH-1V in a prime-and-boost scheme showing PHH-1V to exhibit an excellent safety profile in pigs and to produce a solid RBD-specific humoral response with neutralising antibodies to 7 distinct SARS-CoV-2 variants of concern, with the induction of a significant IFNγ+T-cell response. We conclude that PHH-1V is safe and elicits a robust immune response to SARS-CoV-2 in pigs, a large animal preclinical model.

Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial

“…1.351) and Alpha (B.1.1.7) variants, formulated with an oil-in-water emulsion based on squalene (SQBA) intended for intramuscular administration. [23][24][25] PHH-1V comprises three key mutations of high relevance for previously and currently circulating SARS-CoV-2 variants: K417N, E484K and N501Y. 26 Previous studies revealed that the E484K and N501Y mutations are present in the RBD of the spike protein of Beta, Gamma, and Mu variants; and both the K417N and N501Y mutations present in the PHH-1V antigen are common to the Beta and to the currently predominant Omicron variants.…”

Immunogenicity and safety of an Omicron XBB.1.16 adapted vaccine for COVID-19: Interim results from a randomized, controlled, non-inferiority clinical trial

“…16 Phase IIb trials demonstrated its efficacy in generating neutralizing antibodies against various SARS-CoV-2 variants, including Omicron XBB. [16][17][18] Long-term analysis revealed sustained immune responses, even in high-risk populations regardless of prior infection or primary vaccine type. 19 Additionally, PHH-1V induces a robust T-cell response.…”

“…19 Additionally, PHH-1V induces a robust T-cell response. 17,18 Further, recipients of PHH-1V reported fewer adverse events (AE) than mRNA vaccine recipients, with comparable breakthrough non-severe COVID-19 rates. As a recombinant protein-based vaccine, PHH-1V also may offer advantages, including high productivity, stability, and suitability for immunocompromised individuals, positioning it as a promising candidate in the battle against COVID-19.…”