Humoral and cellular immune responses after 6 months of a heterologous SARS-CoV-2 booster with the protein-based PHH-1V vaccine in a phase IIb trial

The HIPRA-HH-2 was a multicentre, randomized, active-controlled, double-blind, non-inferiority phase IIb clinical trial to compare the immunogenicity and safety of a heterologous booster with PHH-1V adjuvanted recombinant vaccine versus a homologous booster with mRNA vaccine. Interim results showed a strong humoral and cellular immune response against the SARS-CoV-2 Wuhan-Hu-1 strain and the Beta, Delta, and Omicron BA.1 variants up to day 98 after dosing. Here we report that these humoral and cellular responses after PHH-1V dosing are sustained up to 6 months. These results are observed both when including or not participants who reported SARS-CoV-2 infection and in a high-risk population (≥65 years). Additional analysis revealed a non-inferiority of PHH-1V booster in eliciting neutralizing antibodies also for SARS-CoV-2 Omicron XBB.1.5 when compared to mRNA vaccine after 6 months. The PHH-1V vaccine provides long-lasting protection against a wide variety of SARS-CoV-2 emerging variants to prevent severe COVID-19. [ClinicalTrials.gov][1] Identifier: [NCT05142553][2] ### Competing Interest Statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J Blanco has received institutional grants from HIPRA, Grifols, Nesapor Europe and MSD. Outside of this work he is the CEO and founder of AlbaJuna Therapeutics, S.L. A Soriano has received grants from Pfizer and Gilead Sciences and honoraria for lectures for Pfizer, MSD, Gilead Sciences, Shionogi, Angelini, Roche and Menarini. N Izquierdo-Useros declares institutional grants from HIPRA, Pharma Mar, Grifols, and Amassence. J R Arribas has received honoraria for lectures and advisory boards from Janssen, Gilead, MSD, Lilly, Roche, and Pfizer. S Otero-Romero has received speaking and consulting honoraria from Genzyme, Biogen-Idec, Novartis, Roche, Excemed and MSD. J G Prado declares institutional grants from HIPRA and Grifols. AM Borobia is principal investigator of clinical trials sponsored by GlaxoSmithKline, Daiichi-Sankyo and Janssen, outside of the submitted work. J Molto has received honoraria for lectures and advisory boards from Johnson & Johnson, Gilead, and MSD. X Martinez-Gomez has received speaking and consulting honoraria from GSK, Pfizer, and AstraZeneca. J Corominas, C Garriga, A Prenafeta, A Moros, M Canete, A Barreiro, L Gonzalez-Gonzalez, L Madrenas, I Guell, T Prat, E Torroella and L Ferrer are employees of HIPRA. Some of these authors may have shares of HIPRA. Several patent applications have been filed by HIPRA SCIENTIFIC S.L.U. and Laboratorios HIPRA, S.A. on different SARS-CoV-2 vaccine candidates and SARS-CoV-2 subunit vaccines, including the novel recombinant RBD fusion heterodimer PHH-1V. A Barreiro, A Prenafeta, L Gonzalez-Gonzalez, L Ferrer, T Prat and Carme Garriga are the inventors of these patent applications. ### Clinical Trial NCT05142553 ### Funding Statement This study was sponsored by HIPRA SCIENTIFIC, S.L.U (HIPRA) and partially funded by the Centre for the Development of Industrial Technology (CDTI, IDI-20211192), a public organisation answering to the Spanish Ministry of Science and Innovation). HIPRA was involved in the study design; in the collection, analysis, and interpretation of data; in writing of the report; and in the decision to submit the paper for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Independent Ethics Committee from the Hospital Clinic de Barcelona gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data relevant to the study are included in the article or uploaded as supplementary information. Further data are available from the authors upon reasonable request and with permission of HIPRA S.A. [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05142553&atom=%2Fmedrxiv%2Fearly%2F2024%2F02%2F05%2F2024.02.01.24302052.atom