RT Journal Article
SR Electronic
T1 Preclinical efficacy, safety, and immunogenicity of PHH-1V, a second-generation COVID-19 vaccine candidate based on a novel recombinant RBD fusion heterodimer of SARS-CoV-2
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.11.22.469117
DO 10.1101/2021.11.22.469117
A1 Antonio Barreiro
A1 Antoni Prenafeta
A1 Gregori Bech-Sabat
A1 Mercè Roca
A1 Eva Perozo
A1 Ricard March
A1 Luis González
A1 Laia Madrenas
A1 Júlia Corominas
A1 Àlex Fernández
A1 Mercè Molas
A1 Thais Pentinat
A1 Clara Panosa
A1 Alberto Moreno
A1 Ester Puigvert
A1 Eva Pol
A1 Jordi Palmada
A1 Carme Garriga
A1 Teresa Prat
A1 Júlia Vergara-Alert
A1 Cristina Lorca-Oró
A1 Núria Roca
A1 Leira Fernández-Bastit
A1 Jordi Rodon
A1 Mònica Pérez
A1 Joaquim Segalés
A1 Edwards Pradenas
A1 Silvia Marfil
A1 Benjamin Trinité
A1 Raquel Ortiz
A1 Bonaventura Clotet
A1 Julià Blanco
A1 Jorge Díaz Pedroza
A1 Rosa Ampudia Carrasco
A1 Yaiza Rosales Salgado
A1 Jordina Loubat-Casanovas
A1 Sara Capdevila Larripa
A1 Julia Garcia Prado
A1 Jordi Barretina
A1 Marta Sisteré-Oró
A1 Paula Cebollada Rica
A1 Andreas Meyerhans
A1 Laura Ferrer
YR 2021
UL http://biorxiv.org/content/early/2021/12/04/2021.11.22.469117.abstract
AB Since the genetic sequence of SARS-CoV-2 became available in January 2020, new vaccines have been developed at an unprecedented speed. The current vaccines have been directly associated with a decline in new infection rates, prevention of severe disease and an outstanding decrease in mortality rates. However, the pandemic is still far from being over. New Variants of Concern (VoCs) are continuously evolving. Thus, it is essential to develop accessible second-generation COVID-19 vaccines against known and future VoCs to mitigate the current pandemic. Here, we provide preclinical data showing the immunogenicity, efficacy, and safety results in mice of a receptor-binding domain (RBD)-based recombinant protein vaccine candidate (PHH-1V) which consists of a novel RBD fusion heterodimer containing the B.1.1.7 (alpha) and B.1.351 (beta) variants of SARS-CoV-2, formulated with an oil-based adjuvant equivalent to MF59C.1. BALB/c and K18-hACE2 mice were immunized with different doses of recombinant RBD fusion heterodimer, following a two-dose prime-and-boost schedule. Upon 20 μg RBD fusion heterodimer/dose immunization, BALB/c mice produced RBD-binding antibodies with neutralising activity against the alpha, beta, gamma, and delta variants. Furthermore, vaccination elicited robust activation of CD4+ and CD8+ T cells with early expression of Th1 cytokines upon in vitro restimulation, along with a good tolerability profile. Importantly, vaccination with 10 μg or 20 μg RBD fusion heterodimer/dose conferred 100% efficacy preventing mortality and bodyweight loss upon SARS-CoV-2 challenge in K18-hACE2 mice. These findings demonstrate the feasibility of this novel recombinant vaccine strategy, allowing the inclusion of up to 2 different RBD proteins in the same vaccine. Most importantly, this new platform is easy to adapt to future VoCs and has a good stability profile, thus ensuring its global distribution.Competing Interest StatementAuthors indicated as 1 are employees of HIPRA, a private pharmaceutical company that develops and manufactures vaccines. CReSA, IrsiCaixa, CMCiB-IGTP, UPF and ICREA have received financial support from HIPRA.