Safety and immunogenicity of a recombinant protein RBD fusion heterodimer vaccine against SARS-CoV-2
Authors: Leal Lorna , Pich Judit , Ferrer Laura , Nava Jocelyn , Martí-Lluch Ruth , Esteban Ignasi , Pradenas Edwards , Raïch-Regué Dàlia , Prenafeta Antoni , Escobar Karla , Pastor Carmen , Ribas-Aulinas Marc , Trinitè Benjamin , Muñoz-Basagoiti Jordana , Domenech Gemma , Clotet Bonaventura , Corominas Júlia , Corpes-Comes Aida , Garriga Carme , Barreiro Antonio , Izquierdo-Useros Nuria , Arnaiz Joan Albert , Soriano Alex , Ríos José , Nadal Marga , Plana Montserrat , Blanco Julià , Prat Teresa , Torroella Elia , Ramos Rafel ,   HIPRA-HH-1 study group, Bonfill Eva , Anagua Omar , Caicedo Faisury , Castán Clara , Guazina Fauno , Messeguer Sara , Aldea Marta , Vilella Anna , Serrano Sandra , Leal Lorna , Pich Judit , Nava Jocelyn , Escobar Karla , Arnaiz Joan Albert , Soriano Alex , Ríos José , Botta Teresa , Esteban Ignasi , Pastor Carmen , Plana Montserrat , Domenech Gemma , Marfil Silvia , Rovirosa Carla , Ortiz Raquel , Perez-Zsolt Daniel , Gallemí Marçal , Pradenas Edwards , Raïch-Regué Dàlia , Trinité Benjamin , Muñoz-Basagoiti Jordana , Clotet Bonaventura , Izquierdo-Useros Nuria , Blanco Julià , González del Río Marina , Martí-Lluch Ruth , Ribas-Aulinas Marc , Corpes-Comes Aida , Nadal Marga , Ramos Rafel , González Luís , Cañete Manuel , Madrenas Laia , Moros Alexandra , Güell Irina , Ferrer Laura , Prenafeta Antoni , Corominas Júlia , Garriga Carme , Barreiro Antonio , Prat Teresa , Torroella Elia 
Published: September 2023

In response to COVID-19 pandemic, we have launched a vaccine development program against SARS-CoV-2. Here we report the safety, tolerability, and immunogenicity of a recombinant protein RBD fusion heterodimeric vaccine against SARS-CoV-2 (PHH-1V) evaluated in a phase 1-2a dose-escalation, randomized clinical trial conducted in Catalonia, Spain. 30 young healthy adults were enrolled and received two intramuscular doses, 21 days apart of PHH-1V vaccine formulations [10 µg (n = 5), 20 µg (n = 10), 40 µg (n = 10)] or control [BNT162b2 (n = 5)]. Each PHH-1V group had one safety sentinel and the remaining participants were randomly assigned. The primary endpoint was solicited events within 7 days and unsolicited events within 28 days after each vaccination. Secondary endpoints were humoral and cellular immunogenicity against the variants of concern (VOCs) alpha, beta, delta and gamma. All formulations were safe and well tolerated, with tenderness and pain at the site of injection being the most frequently reported solicited events. Throughout the study, all participants reported having at least one mild to moderate unsolicited event. Two unrelated severe adverse events (AE) were reported and fully resolved. No AE of special interest was reported. Fourteen days after the second vaccine dose, all participants had a >4-fold change in total binding antibodies from baseline. PHH-1V induced robust humoral responses with neutralizing activities against all VOCs assessed (geometric mean fold rise at 35 days p < 0.0001). The specific T-cell response assessed by ELISpot was moderate. This initial evaluation has contributed significantly to the further development of PHH-1V, which is now included in the European vaccine portfolio.

ClinicalTrials.gov Identifier NCT05007509

EudraCT No. 2021-001411-82