Safety and Cross-Neutralizing Immunity Against SARS-CoV-2 Omicron Sub-Variant After a Booster Dose with SOBERANA^®...

Background: With the emergence of SARS-CoV-2 Omicron sub-variants exhibiting increased transmissibility and immune escape, booster immunization is recommended. Ideally, vaccination across all age groups, including children and adolescents, is critical to control viral spread and reduce variant emergence. The heterologous scheme consisting of two doses of SOBERANA^® 02 followed by a third dose of SOBERANA^® Plus, which are recombinant protein subunit vaccines constructed from the ancestral RBD, has proven safety, immunogenicity, and effectiveness in pediatric populations as primary series. This study evaluated the safety and immunogenicity of a SOBERANA^® Plus booster dose administered six months after primary vaccination in individuals aged 3-18 years. Methods: In this follow-up analysis of a phase I/II trial, 244 participants received the booster. Safety was monitored via active surveillance at 1 h, 24 h, and over 28 days post-vaccination. Humoral responses were assessed 28 days post-booster. Antibody responses to the SARS-CoV-2 nucleocapsid (N) protein were assessed in all collected serum samples. Results: Adverse events occurred in 18% of participants, predominantly local (85.2%) versus systemic (14.8%); no serious or severe adverse events were reported. All humoral response parameters increased significantly post-booster, including neutralizing antibodies against D614G (24.7-fold increase) and Omicron BA.1 (55.9-fold increase), with similar responses in N-negative and N-positive individuals. Importantly, cross-neutralizing activity against recent Omicron sub-variants (XBB.1.5 and EG.5.1) was also detected. Conclusions: A SOBERANA^® Plus booster is safe and significantly enhances cross-neutralizing immunity against evolving Omicron sub-variants in children and adolescents. These results highlight the potential of first-generation RBD-based vaccines to maintain broad immunity despite viral evolution.