Safety and immunogenicity of a phh-1v booster dose after different prime vaccination schemes against covid-19: phase iii clinical trial final results up to one year

In this phase III, open label, single arm, multicenter clinical study, we report safety, tolerability and immunogenicity of PHH-1V as a booster dose in subjects primary vaccinated against COVID-19 with the BNT162b2, mRNA-1273, ChAdOx1-S, or Ad26.COV2.S vaccines, with or without previous COVID-19 infection. A total of 2661 subjects were included in this study and vaccinated with the PHH-1V vaccine. Most treatment-emergent adverse events (TEAE) were solicited local and systemic reactions with grade 1 (58.70%) or grade 2 (27.58%) intensity, being the most frequently reported injection site pain (82.83%), fatigue (31.72%) and headache (31.23%). Additionally, immunogenicity was assessed at Baseline and Days 14, 91, 182 and 365 in a subset of 235 subjects primary vaccinated. On Day 14, geometric mean triter (GMT) in neutralizing antibody against SARS-CoV-2 Wuhan and Beta, Delta and Omicron BA.1 variants increased in all primary vaccination with a geometric mean fold raise (GMFR) of 6.90 (95% CI 4.96-9.58), 12.27 (95% CI 8.52-17.67), 7.24 (95% CI 5.06-10.37) and 17.51 (95% CI 12.28-24.97), respectively. Despite GMT decay after day 14, it remains in all cases significatively higher from baseline up to 1 year after PHH-1V booster administration and GMFR against Beta and Omicron BA.1 variants over 3 at 1 year after booster compared to baseline. PHH-1V booster vaccination elicited also a significant RBD/Spike-specific IFN-γ+ T-cell responses on Day 14. Overall, PHH-1V vaccine was immunogenic and well-tolerated regardless of the previous primary vaccination scheme received with no reported cases of severe COVID-19 infection throughout the entire study. ### Competing Interest Statement The authors of this manuscript declare SNM declares that her institution received payment from HIPRA for conducting this trial, from Pfizer, Sanofi, MSD, GSK, Janssen, AstraZeneca and Moderna for other vaccines trials and participation on data safety monitoring boards or advisory boards for GSK. AS has received grants from Pfizer and Gilead Sciences and honoraria for lectures for Pfizer, MSD, Gilead Sciences, Shionogi, Angelini, Roche and Menarini. NIU is supported by the Spanish Ministry of Science and Innovation (grant PID2020-117145RB-I00, Spain), EU HORIZON-HLTH-2021CORONA-01 (grant 101046118, European Union) and by institutional funding of Pharma Mar, HIPRA, and Amassence.. JRA has received honoraria for lectures and advisory boards from Janssen, Gilead, MSD, Lilly, Roche and Pfizer. SOR has received speaking and consulting honoraria from Genzyme, Biogen-Idec, Novartis, Roche, Excemed and MSD. JGP declares institutional grants from HIPRA and Grifols. ### Clinical Trial NCT05303402 ### Funding Statement This work was supported by HIPRA SCIENTIFIC, S.L.U (HIPRA) and partially funded by the Centre for the Development of Industrial Technology (CDTI, IDI-20211192), a public organization answering to the Spanish Ministry of Science and Innovation. ### 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 study protocol, informed consent form (ICF), and written information given to subjects were reviewed and approved by an appropriately constituted Institutional Review Board (IRB) and the Independent Ethics Committee (IEC) from Spain and Italy (IEC Hospital Clinic de Barcelona, and IEC LAZZARO SPALLANZANI, IRCCS). 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.