Preclinical evaluation of PHH-1V vaccine candidate against SARS-CoV-2 in non-human primates

Prenafeta, Antoni; Bech-Sàbat, G.; Moros, Alexandra; Barreiro, Antonio; Fernández, Alex; Cañete, Manuel; Roca, María J.; González, Luís Javier Durán; Garriga, Carme; Confais, Joachim; Toussenot, Marion; Contamin, Hugues; Pradenas, Edwards; Marfil, Sílvia; Blanco, Julià; Rica, Paula Cebollada; Sisteré-Oró, Marta; Meyerhans, Andreas; Pizzorno, Andrés; Rosa‐Calatrava, Manuel; Cabañas, Teresa Prat; March, Ricard; Ferrer, Laura

doi:10.1101/2022.12.13.520255

Cited by 3 publications

(1 citation statement)

References 52 publications

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“…This vaccine is based on a fusion heterodimer consisting of the spike RBD sequence from the SARS-CoV-2 Beta (B.1.351) and Alpha (B.1.1.7) variants, formulated with an oil-in-water emulsion based on squalene (SQBA) intended for intramuscular administration. 23-25 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.…”

Section: Introductionmentioning

confidence: 99%

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

Corominas

Garriga

Prenafeta

et al. 2022

Preprint

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SummaryBackgroundA SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14 and 98 days after vaccine administration.MethodsThe HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine – either heterologous (PHH-1V group) or homologous (BNT162b2 group) – in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies against the ancestral Wuhan-Hu-1 strain and different variants of SARS-CoV-2 after the PHH-1V or the BNT162b2 boost, the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides and the safety and tolerability of PHH-1V as a boost. This study is ongoing and is registered with ClinicalTrials.gov, NCT05142553.FindingsFrom 15 November 2021, 782 adults were randomly assigned to PHH-1V (n=522) or BNT162b2 (n=260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1·68 (p<0·0001) and 0·87 (p=0·43) for the ancestral Wuhan-Hu-1 strain; 0·61 (p<0·0001) and 0·57 (p=0·0064) for the beta variant; 1·01 (p=0·89) and 0·52 (p=0·0003) for the delta variant; and 0·59 (p=<0·0001) and 0·56 (p=0·0026) for the omicron variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4+ and CD8+ T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89·3%) in the PHH-1V and 238 (94·4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79·7% and 89·3%), fatigue (27·5% and 42·1%) and headache (31·2 and 40·1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10·14%) for the PHH-1V group and 30 (11·90%) for the BNT162b2 group (p=0·45), and none of the subjects developed severe COVID-19.InterpretationOur interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, elicits a strong and sustained neutralizing antibody response against Wuhan-Hu-1 strain, and a superior one concerning the previous circulating beta and delta SARS-CoV-2 variants, as well as the currently circulating omicron. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe.FundingHIPRA SCIENTIFIC, S.L.U.

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Section: Introductionmentioning

confidence: 99%

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

Corominas

Garriga

Prenafeta

et al. 2022

Preprint

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Peptide delivery of a multivalent mRNA SARS-CoV-2 vaccine

McCrudden,

Bennie,

Chambers

et al. 2023

Journal of Controlled Release

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

Moros¹,

Prenafeta²,

Barreiro³

et al. 2023

Preprint

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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.

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Preclinical evaluation of PHH-1V vaccine candidate against SARS-CoV-2 in non-human primates

Cited by 3 publications

References 52 publications

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

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

Peptide delivery of a multivalent mRNA SARS-CoV-2 vaccine

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

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