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.
Keywords: COVID-19; Protein vaccine; SARS-CoV-2; omicron subvariants; vaccine booster.