Safety and immunogenicity of PHH-1V booster against SARS-CoV-2 variants, including omicron subvariants: Results from a phase IIb open-label extension study

• Published in: Human vaccines & immunotherapeutics Vol. 21; no. 1; p. 2474775
• Main Authors: López, María Jesús, Vazquez, Maria Del Mar, Alvarez-Mon, Melchor, Arribas, José Ramón, Arana-Arri, Eunate, Muñoz, Patricia, Navarro-Pérez, Jorge, Ramos, Rafael, Molto, José, Otero-Romero, Susana, Aurrecoechea, Elena, Pomarol, Roc, Bernad, Laia, Esteban, Ignasi, Pérez-Caballero, Raúl, Plana, Montserrat, Prado, Júlia G., Soriano, Álex
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.12.2025; Taylor & Francis Group
• Subjects: Adult; Aged; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibodies, Viral - blood; Antibodies, Viral - immunology; BNT162 Vaccine - administration & dosage; BNT162 Vaccine - immunology; Coronavirus; COVID-19; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 Vaccines - administration & dosage; COVID-19 Vaccines - adverse effects; COVID-19 Vaccines - immunology; Female; Humans; Immunization, Secondary - adverse effects; Immunization, Secondary - methods; Immunogenicity, Vaccine; Male; Middle Aged; omicron subvariants; Protein vaccine; SARS-CoV-2; SARS-CoV-2 - immunology; Spain; vaccine booster; Young Adult; Spain; COVID-19; SARS-CoV-2; Protein vaccine; omicron subvariants; vaccine booster
• ISSN: 2164-5515; 2164-554X; 2164-554X
• DOI: 10.1080/21645515.2025.2474775

SARS-CoV-2 vaccination campaigns on current endemic situation would benefit from vaccine alternatives with easy logistics and accessibility, sustained response and cross-reactivity against emerging variants. Herein, safety and immunogenicity of PHH-1V, adjuvanted recombinant RBD-based vaccine, as fourth dose for the most prevalent SARS-CoV-2 variants in Spain in subjects ≥18 years was investigated for 6 months in HIPRA-HH-2 open-label extension study. Subjects received a fourth dose of PHH-1V after either two BNT162b2 doses plus one PHH-1V dose (cohort 1) or three BNT162b2 doses (cohort 2). As regulatory endpoint, neutralization titers were investigated for PHH-1 V as fourth dose vs BNT162b2 as third dose in subjects receiving previous BNT162b2-based regimens. PHH-1 V immunogenicity (GMT) was investigated against Beta, Delta, and Omicron BA.1, BA.4/5 and XBB.1.5 on Days 14, 98 and 182 post-immunization. Two hundred and eighty-eight subjects received PHH-1V. Neutralizing antibodies against Omicron BA.1 at Day 14 significantly increased after the PHH-1V as fourth booster vs the third BNT162b2 booster (GMT ratio 0.43 (95% CI: 0.28; 0.65; p-value < .0001)). PHH-1V fourth booster induced a significant increase in neutralizing titers vs baseline (GMFR on Day 14 [95% CI]: Beta 6.96 [5.23, 9.25]; Delta 6.27 [4.79, 8.22]; Omicron BA.1 9.21 [5.57, 15.21]; Omicron BA.4/5 11.80 [8.29, 16.80]; Omicron XBB.1.5 5.22 [3.97, 6.87]), remaining significantly higher up to 6 months. The most frequent adverse events were injection site pain and fatigue. As conclusion, PHH-1V booster induced sustained humoral and cellular immune response against Beta, Delta variants and cross reactivity against distant Omicron subvariants and could be an appropriate strategy for implementing heterologous vaccination campaigns.